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About jppres

The Journal of Pharmacy & Pharmacognosy Research (JPPRes) is an international, specialized and peer-reviewed open access journal, which publishes studies in the pharmaceutical and herbal fields concerned with the physical, botanical, chemical, biological, toxicological properties and clinical applications of molecular entities, active pharmaceutical ingredients, devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture, evaluation and marketing. This journal publishes research papers, reviews, commentaries and letters to the editor as well as special issues and review of pre-and post-graduate thesis from pharmacists or professionals involved in Pharmaceutical Sciences or Pharmacognosy.

Medicinal plants against new-world cutaneous leishmaniasis

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 975-1001, Nov-Dec 2023.

DOI: https://doi.org/10.56499/jppres23.1697_11.6.975

Review

Medicinal plants with antileishmanial activity on parasites responsible for new-world cutaneous leishmaniasis. A systematic review 2018-2022

[Plantas medicinales con actividad antileishmania sobre parásitos responsables de leishmaniasis cutánea del nuevo mundo. Una revisión sistemática 2018-2022]

Yenny Y. Lozano1, Sara E. Giraldo1, Angela C. Zapata1, Jesús E. Escobar1, Ruth M. Sánchez2*

1Universidad de La Salle, Bogotá, D.C., Colombia.

2Universidad Colegio Mayor de Cundinamarca, Bogotá, D.C., Colombia.

*E-mail: rmsanchezm@unicolmayor.edu.co

Abstract

Context: Cutaneous leishmaniasis is a disease of public health importance; treatment is based on the use of pentavalent antimonials with high toxicity and low efficacy; therefore, it´s necessary to search for therapeutic alternatives derived from natural products, based on the study of medicinal plants as a source of molecules with highly effective leishmanicidal potential.

Aims: To carry out a systematic review between 2018 and 2022 on medicinal plants with potential leishmanicidal activity on parasite strains from the New World causing cutaneous leishmaniasis.

Methods: The review study was conducted in four phases following the PRISMA methodology. First, research questions and objectives were formulated to establish the topic areas and construct the search algorithm. Second, a search was performed across different databases, including ScienceDirect, Scopus, PubMed, Web of Science, EBSCO, Taylor and Francis, and Scielo. Third, articles were chosen based on specific inclusion and exclusion criteria. Finally, the relevant information for the review was systematically organized.

Results: The search yielded 163 articles, and 12 of them were selected as the basis for the construction of the review. Ethanolic and aqueous extracts stand out, as well as biocompounds such as terpenes and flavonoids. Antioxidant activity on reactive oxygen species was the most frequently cited.

Conclusions: Promising terpene and flavonoid molecules with high antileishmanial activity (IC50 <2 μM or <10 μg/mL and SI >1) were identified in this study; these findings provide a scientific basis for the traditional use that communities have given to plants as a therapeutic source to treat cutaneous leishmaniasis in the New World.

Keywords: antiprotozoal agents; cutaneous; Leishmania; leishmaniasis; plant extracts.

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Resumen

Contexto: La leishmaniasis cutánea es una enfermedad de importancia en salud pública; su tratamiento se basa en el uso de antimoniales pentavalentes con alta toxicidad y baja eficacia; por tanto, es necesaria la búsqueda de alternativas terapéuticas derivadas de productos naturales, a partir del estudio de plantas medicinales como fuente de moléculas con potencial leishmanicida.

Objetivos: Realizar una revisión sistemática comprendida entre los años 2018-2022 referente a plantas medicinales con potencial actividad leishmanicida sobre cepas parasitarias del nuevo mundo causales de leishmaniasis cutánea.

Métodos: La revisión se realizó en cuatro fases siguiendo la metodología PRISMA. En primer lugar, se formularon las preguntas de investigación y los objetivos para establecer las áreas temáticas y construir el algoritmo de búsqueda. En segundo lugar, se realizó una búsqueda en diferentes bases de datos, como ScienceDirect, Scopus, PubMed, Web of Science, EBSCO, Taylor and Francis y Scielo. En tercer lugar, se seleccionaron los artículos en función de criterios específicos de inclusión y exclusión. Por último, la información relevante se organizó sistemáticamente para la revisión.

Resultados: La búsqueda arrojó 163 artículos, definiendo 12 artículos base para la construcción de la revisión. Sobresalen los extractos etanólicos y acuosos; así como biocompuestos tipo terpenos y flavonoides. La actividad antioxidante sobre especies reactivas de oxígeno fue la más citada.

Conclusiones: Se identificaron moléculas promisorias con alta actividad antileishmania (CI50 <2 μM o <10 μg/mL y con IS >1) tipo terpenos y flavonoides; resultado que brinda una base científica para el uso tradicional que las comunidades le han dado a las plantas como fuente terapéutica para tratar la leishmaniasis cutánea en el nuevo mundo.

Palabras Clave: agentes antiprotozoarios; cutáneo; extractos de plantas; Leishmania; leishmaniasis.

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Citation Format: Lozano YY, Giraldo SG, Zapata AC, Escobar JE, Sánchez RM (2023) Medicinal plants with antileishmanial activity on parasites responsible for new-world cutaneous leishmaniasis. A systematic review 2018-2022. J Pharm Pharmacogn Res 11(6): 975–1001. https://doi.org/10.56499/jppres23.1697_11.6.975
References

Al-Dabbagh B, Elhaty IA, Elhaw M, Murali C, Al Mansoori A, Awad B, Amin A (2019) Antioxidant and anticancer activities of chamomile (Matricaria recutita L.). BMC Res Notes 12(1): 3. https://doi.org/10.1186/s13104-018-3960-y

Alexander J, Satoskar A R, Russell DG (1999) Leishmania species: models of intracellular parasitism. J Cell Sci 112 Pt 18: 2993–3002. https://doi.org/10.1242/jcs.112.18.2993

Ali EMM, Almagboul AZI, Khogali SME, Gergeir UMA (2012) Antimicrobial activity of Cannabis sativa L. Chinese Med 3(1): 61–64. https://doi.org/10.4236/cm.2012.31010

Alvar J, Croft S, Olliaro P (2006a) Chemotherapy in the treatment and control of leishmaniasis. Adv Parasitol 61: 223–274. https://doi.org/10.1016/S0065-308X(05)61006-8

Alvar J, Yactayo S, Bern C (2006b) Leishmaniasis and poverty. Trends Parasitol 22(12): 552–557. https://doi.org/10.1016/j.pt.2006.09.004

Alves DR, Maia de Morais S, Tomiotto-Pellissier F, Miranda-Sapla MM, Vasconcelos FR, da Silva ING, Araujo de Sousa H, Assolini JP, Conchon-Costa I, Pavanelli WR, Freire F (2017) Flavonoid composition and biological activities of ethanol extracts of Caryocar coriaceum Wittm., a native plant from Caatinga Biome. Evid Based Complement Alternat Med 2017: 7. https://doi.org/10.1155/2017/6834218

Amsterdam JD, Shults J, Soeller I, Mao JJ, Rockwell K, Newberg AB (2012) Chamomile (Matricaria recutita) may provide antidepressant activity in anxious, depressed humans: an exploratory study. Altern Ther Health Med 18(5): 44–49. https://pubmed.ncbi.nlm.nih.gov/22894890/

Andrade PM, Melo DC, Alcoba AET, Ferreira Junior WG, Pagotti MC, Magalhaes LG, Santos T, Crotti AEM, Alves CCF, Miranda MLD (2018) Chemical composition and evaluation of antileishmanial and cytotoxic activities of the essential oil from leaves of Cryptocarya aschersoniana Mez. (Lauraceae Juss.). An Acad Bras Cienc 90(3): 2671–2678. https://doi.org/10.1590/0001-3765201820170332

Aragão Macedo SR, Ferreira AS, Biguinati de Barros N, Ulisses de Oliveira Meneguetti D, Facundo VA, Shibayama TY, Nicolete R (2019) Evaluation of the antileishmanial activity of biodegradable microparticles containing a hexanic eluate subfraction of Maytenus guianensis bark. Exp Parasitol 205: 107738. https://doi.org/10.1016/j.exppara.2019.107738

Araújo-Vilges KM, Oliveira SV, Couto SCP, Fokoue HH, Romero GAS, Kato MJ, Romeiro LAS, Leite J, Kuckelhaus SAS (2017) Effect of piplartine and cinnamides on Leishmania amazonensis, Plasmodium falciparum and on peritoneal cells of Swiss mice. Pharm Biol 55(1): 1601–1607. https://doi.org/10.1080/13880209.2017.1313870

Arevalo J, Ramirez L, Adaui V, Zimic M, Tulliano G, Miranda-Verastegui C, Lazo M, Loayza-Muro R, De Doncker S, Maurer A, Chappuis F, Dujardin J C, Llanos-Cuentas A (2007) Influence of Leishmania (Viannia) species on the response to antimonial treatment in patients with American tegumentary leishmaniasis. J Infect Dis 195(12): 1846–1851. https://doi.org/10.1086/518041

Arruda DC, D’Alexandri F L, Katzin AM, Uliana SR (2005) Antileishmanial activity of the terpene nerolidol. Antimicrob Agents Chemother 49(5): 1679–1687. https://doi.org/10.1128/AAC.49.5.1679-1687.2005

Arruda DC, Miguel DC, Yokoyama-Yasunaka JK, Katzin AM, Uliana SR (2009) Inhibitory activity of limonene against Leishmania parasites in vitro and in vivo. Biomed Pharmacother 63(9): 643–649. https://doi.org/10.1016/j.biopha.2009.02.004

Autran ES, Neves IA, da Silva CS, Santos GK, da Câmara CA, Navarro DM (2009) Chemical composition, oviposition deterrent and larvicidal activities against Aedes aegypti of essential oils from Piper marginatum Jacq. (Piperaceae). Bioresour Technol 100(7): 2284–2288. https://doi.org/10.1016/j.biortech.2008.10.055

Barbosa WL, Pinto L, Quignard E, Vieira J, Silva Jr J, Albuquerque S (2008) Arrabidaea chica (HBK) Verlot: Phytochemical approach, antifungal and trypanocidal activities. Rev Bras Farmacogn 18(4): 544–548. https://doi.org/10.1590/S0102-695X2008000400008

Barrera P, Sulsen VP, Lozano E, Rivera M, Beer MF, Tonn C, Martino VS, Sosa MA (2013) Natural sesquiterpene lactones induce oxidative stress in Leishmania mexicana. Evid Based Complement Alternat Med 2013: 163404. https://doi.org/10.1155/2013/163404

Barros LM, Duarte AE, Morais-Braga MF, Waczuk EP, Vega C, Leite NF, de Menezes IR, Coutinho HD, Rocha JB, Kamdem JP (2016) Chemical characterization and trypanocidal, leishmanicidal and cytotoxicity potential of Lantana camara L. (Verbenaceae) essential oil. Molecules 21(2): 209. https://doi.org/10.3390/molecules21020209

Boniface PK, Ferreira EI (2019) Flavonoids as efficient scaffolds: Recent trends for malaria, leishmaniasis, Chagas disease, and dengue. Phytother Res 33(10): 2473–2517. https://doi.org/10.1002/ptr.6383

Bosquiroli LSS, Demarque DP, Rizk YS, Cunha MC, Marques MCS, Matos MdFC, Kadri MCT, Carollo CA, Arruda CCP (2015) In vitro anti-Leishmania infantum activity of essential oil from Piper angustifolium. Rev Bras Farmacogn 25(2): 124–128. https://doi.org/10.1016/j.bjp.2015.03.008

Brito LM, Alves MMdM, Souza AC, Carvalho TPd, Campos JHF, Monção NBN, Citó AMdGL, Arcanjo DDR, Carvalho FAdA (2021) Selective in vitro antileishmanial activity of Mimosa caesalpiniifolia stem barks and its main constituent betulinic acid against Leishmania amazonensis. S Afr J Bot 140: 68–75. https://doi.org/10.1016/j.sajb.2021.03.028

Brú J, Guzman JD (2016) Folk medicine, phytochemistry and pharmacological application of Piper marginatum. Rev Bras Farmacogn 26(6):767–779. https://doi.org/10.1016/j.bjp.2016.03.014

Caldas LA, Yoshinaga ML, Ferreira MJP, Lago JHG, de Souza AB, Laurenti MD, Passero LFD, Sartorelli P (2019) Antileishmanial activity and ultrastructural changes of sesquiterpene lactones isolated from Calea pinnatifida (Asteraceae). Bioorg Chem 83: 348–353. https://doi.org/10.1016/j.bioorg.2018.10.059

Carneiro SM, Carvalho FA, Santana LC, Sousa AP, Neto JM, Chaves MH (2012) The cytotoxic and antileishmanial activity of extracts and fractions of leaves and fruits of Azadirachta indica (A Juss.). Biol Res 45(2): 111–116. https://doi.org/10.4067/S0716-97602012000200002

Chahed MK, Bellali H, Ben Jemaa S, Bellaj T (2016) Psychological and psychosocial consequences of zoonotic cutaneous leishmaniasis among women in Tunisia: Preliminary findings from an exploratory study. PLoS Negl Trop Dis 10(10): e0005090. https://doi.org/10.1371/journal.pntd.0005090

Chhetri BK, Ali NAA, Setzer WN (2015) A survey of chemical compositions and biological activities of Yemeni aromatic medicinal plants. Medicines (Basel) 2(2): 67–92. https://doi.org/10.3390/medicines2020067

Claborn DM (2010) The biology and control of leishmaniasis vectors. J Glob Infect Dis 2(2): 127–134. https://doi.org/10.4103/0974-777X.62866

Colotti G, Ilari A (2011) Polyamine metabolism in Leishmania: From arginine to trypanothione. Amino Acids 40(2): 269–85. https://doi.org/10.1007/s00726-010-0630-3

Corpas-Lopez V, Merino-Espinosa G, Lopez-Viota M, Gijon-Robles P, Morillas-Mancilla MJ, Lopez-Viota J, Diaz-Saez V, Morillas-Marquez F, Navarro Moll MC, Martin-Sanchez J (2016) Topical treatment of Leishmania tropica infection using (-)-alpha-bisabolol ointment in a hamster model: Effectiveness and safety assessment. J Nat Prod 79(9): 2403–2407. https://doi.org/10.1021/acs.jnatprod.6b00740

Corpas-Lopez V, Morillas-Marquez F, Navarro-Moll MC, Merino-Espinosa G, Diaz-Saez V, Martin-Sanchez J (2015) (-)-alpha-Bisabolol, a Promising oral compound for the treatment of visceral leishmaniasis. J Nat Prod 78(6): 1202–1207. https://doi.org/10.1021/np5008697

Costa E, Belem Pinheiro M, Silva J, Maia B, Duarte M, Amaral A, Machado G, Leon L (2009) Antimicrobial and antileishmanial activity of essential oil from the leaves of Annona foetida (Annonaceae). Quim Nova 32(1): 78–81. https://doi.org/10.1590/S0100-40422009000100015

Cox-Georgian D, Ramadoss N, Dona C, Basu C (2019) Therapeutic and medicinal uses of terpenes. In: Joshee N, Dhekney S, Parajuli P (eds) Medicinal Plants. Springer, Cham, p. 333–359. https://doi.org/10.1007/978-3-030-31269-5_15

Craciunescu O, Constantin D, Gaspar A, Toma L, Utoiu E, Moldovan L (2012) Evaluation of antioxidant and cytoprotective activities of Arnica montana L. and Artemisia absinthium L. ethanolic extracts. Chem Cent J 6(1): 97. https://doi.org/10.1186/1752-153X-6-97

Da Costa FB, Terfloth L, Gasteiger J (2005) Sesquiterpene lactone-based classification of three Asteraceae tribes: A study based on self-organizing neural networks applied to chemosystematics. Phytochemistry 66(3): 345–353. https://doi.org/10.1016/j.phytochem.2004.12.006

da Silva ER, Brogi S, Grillo A, Campiani G, Gemma S, Vieira PC, Maquiaveli CDC (2019) Cinnamic acids derived compounds with antileishmanial activity target Leishmania amazonensis arginase. Chem Biol Drug Des 93(2): 139–146. https://doi.org/10.1111/cbdd.13391

da Silva MA, Fokoue HH, Fialho SN, Dos Santos APA, Rossi N, Gouveia AJ, Ferreira AS, Passarini GM, Garay AFG, Alfonso JJ, Soares AM, Zanchi FB, Kato MJ, Teles CBG, Kuehn CC (2021) Antileishmanial activity evaluation of a natural amide and its synthetic analogs against Leishmania (V.) braziliensis: An integrated approach in vitro and in silico. Parasitol Res 120(6): 2199–2218. https://doi.org/10.1007/s00436-021-07169-w

Danelli MG, Soares DC, Abreu HS, Pecanha LM, Saraiva EM (2009) Leishmanicidal effect of LLD-3 (1), a nor-triterpene isolated from Lophanthera lactescens. Phytochemistry 70(5): 608–614. https://doi.org/10.1016/j.phytochem.2009.03.009

D’Angelo LC, Xavier HS, Torres LM, Lapa AJ, Souccar C (1997) Pharmacology of Piper marginatum Jacq. a folk medicinal plant used as an analgesic, antiinflammatory and hemostatic. Phytomedicine 4(1): 33–40. https://doi.org/10.1016/S0944-7113(97)80025-6

de Araujo FF, Neri-Numa IA, de Paulo Farias D, da Cunha G, Pastore GM (2019) Wild Brazilian species of Eugenia genera (Myrtaceae) as an innovation hotspot for food and pharmacological purposes. Food Res Int 121: 57–72. https://doi.org/10.1016/j.foodres.2019.03.018

de Araújo VE, Morais MH, Reis IA, Rabello A, Carneiro M (2012) Early clinical manifestations associated with death from visceral leishmaniasis. PLoS Negl Trop Dis 6(2): e1511. https://doi.org/10.1371/journal.pntd.0001511

De Lima JPS, Pinheiro MLB, Santos AMG, Pereira JLdaS, Santos DMF, Barison A, Silva-Jardim I, Costa EV (2012) In vitro antileishmanial and cytotoxic activities of Annona mucosa (Annonaceae). Rev Virtual Quim 4(6): 692–702. https://dx.doi.org/10.5935/1984-6835.20120052

de Oliveira ML, Nunes-Pinheiro DC, Tome AR, Mota EF, Lima-Verde IA, Pinheiro FG, Campello CC, de Morais SM (2010) In vivo topical anti-inflammatory and wound healing activities of the fixed oil of Caryocar coriaceum Wittm. seeds. J Ethnopharmacol 129(2): 214–219. https://doi.org/10.1016/j.jep.2010.03.014

de Sousa SM, Reis AC, Viccini LF (2013) Polyploidy, B chromosomes, and heterochromatin characterization of Mimosa caesalpiniifolia Benth. (Fabaceae-Mimosoideae). Tree Genet Genomes 9(2): 613–619. https://doi.org/10.1007/s11295-012-0567-7

de Souza AM, de Oliveira CF, de Oliveira VB, Betim FCM, Miguel OG, Miguel MD (2018) Traditional uses, phytochemistry, and antimicrobial activities of Eugenia species – A review. Planta Med 84(17): 1232–1248. https://doi.org/10.1055/a-0656-7262

de Toledo J S, Ambrosio S R, Borges C H, Manfrim V, Cerri D G, Cruz A K, Da Costa F B (2014) In vitro leishmanicidal activities of sesquiterpene lactones from Tithonia diversifolia against Leishmania braziliensis promastigotes and amastigotes. Molecules 19(5): 6070–6079. https://doi.org/10.3390/molecules19056070

Delgado-Altamirano R, Lopez-Palma RI, Monzote L, Delgado-Dominguez J, Becker I, Rivero-Cruz JF, Esturau-Escofet N, Vazquez-Landaverde PA, Rojas-Molina A (2019) Chemical constituents with leishmanicidal activity from a pink-yellow cultivar of Lantana camara var. aculeata (L.) collected in Central Mexico. Int J Mol Sci 20(4): 872. https://doi.org/10.3390/ijms20040872

Dellacasa A, Bailac P, Ponzi M, Ruffinengo S, Eguaras M (2003) In vitro activity of essential oils from San Luis-Argentina against Ascosphaera apis. J Essent Oil Res 15(4): 282–285. https://doi.org/10.1080/10412905.2003.9712143

Demarchi IG, Thomazella MV, de Souza Terron M, Lopes L, Gazim ZC, Cortez DA, Donatti L, Aristides SM, Silveira TG, Lonardoni MV (2015) Antileishmanial activity of essential oil and 6,7-dehydroroyleanone isolated from Tetradenia riparia. Exp Parasitol 157: 128–137. https://doi.org/10.1016/j.exppara.2015.06.014

Desjeux P (1999) Global control and Leishmania HIV co-infection. Clin Dermatol 17(3): 317–325. https://doi.org/10.1016/S0738-081X(99)00050-4

Dias CN, Alves LP, Rodrigues KA, Brito MC, Rosa Cdos S, do Amaral FM, Monteiro Odos S, Andrade EH, Maia JG, Moraes DF (2015) Chemical composition and larvicidal activity of essential oils extracted from Brazilian legal amazon plants against Aedes aegypti L. (Diptera: Culicidae). Evid Based Complement Alternat Med 2015: 490765. https://doi.org/10.1155/2015/490765

do Nascimento Silva J, Drumond RR, Monção NBN, Paula A, Ferreira P (2016) Prospective study about antineoplasic properties of plants from Fabaceae family: Emphasis in Mimosa caesalpiniifolia. Geintec 6(3): 3304–3318. https://doi.org/10.7198/S2237-072220160003005

do Socorro SRMS, Mendonça-Filho RR, Bizzo HR, de Almeida Rodrigues I, Soares RM, Souto-Padrón T, Alviano CS, Lopes AH (2003) Antileishmanial activity of a linalool-rich essential oil from Croton cajucara. Antimicrob Agents Chemother 47(6): 1895–1901. https://doi.org/10.1128/AAC.47.6.1895-1901.2003

Docampo R (2000) New and re-emerging diseases: a dedication to Norman D. Levine. Parasitol Today 16(8): 316–317. https://doi.org/10.1016/s0169-4758(00)01718-x

Dostálová A, Volf P (2012) Leishmania development in sand flies: parasite-vector interactions overview. Parasites Vectors 5: 276. https://doi.org/10.1186/1756-3305-5-276

Downes MJ, Brennan ML, Williams HC, Dean RS (2016) Development of a critical appraisal tool to assess the quality of cross-sectional studies (AXIS). BMJ Open 6(12): e011458. http://dx.doi.org/10.1136/bmjopen-2016-011458

El Asbahani A, Miladi K, Badri W, Sala M, Ait Addi EH, Casabianca H, El Mousadik A, Hartmann D, Jilale A, Renaud FN, Elaissari A (2015) Essential oils: from extraction to encapsulation. Int J Pharm 483(1-2): 220–243. https://doi.org/10.1016/j.ijpharm.2014.12.069

El-Mougy NS (2009) Effect of some essential oils for limiting early blight (Alternaria solani) development in potato field. J Plant Prot Res 49(1): 57–62. https://doi.org/10.2478/v10045-009-0008-2

ElSohly MA, Slade D (2005) Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci 78(5): 539–548. https://doi.org/10.1016/j.lfs.2005.09.011

Elzinga S, Fischedick J, Podkolinski R, Raber J (2015) Cannabinoids and terpenes as chemotaxonomic markers in Cannabis. Nat Prod Chem Res 3(4): 1000181. https://doi.org/10.4172/2329-6836.1000181

Emerenciano VP, Militão JSLT, Campos CC, Romoff P, Kaplan MAC, Zambon M, Brant AJC (2001) Flavonoids as chemotaxonomic markers for Asteraceae. Biochem Syst Ecol 29(9): 947–957. https://doi.org/10.1016/S0305-1978(01)00033-3

Fadel H, Sifaoui I, Lopez-Arencibia A, Reyes-Batlle M, Hajaji S, Chiboub O, Jimenez IA, Bazzocchi IL, Lorenzo-Morales J, Benayache S, Pinero JE (2018) Assessment of the antiprotozoal activity of Pulicaria inuloides extracts, an Algerian medicinal plant: Leishmanicidal bioguided fractionation. Parasitol Res 117(2): 531–537. https://doi.org/10.1007/s00436-017-5731-4

Fadel H, Sifaoui I, Lopez-Arencibia A, Reyes-Batlle M, Jimenez IA, Lorenzo-Morales J, Ghedadba N, Benayache S, Pinero JE, Bazzocchi IL (2019) Antioxidant and leishmanicidal evaluation of Pulicaria Inuloides root extracts: A bioguided fractionation. Pathogens 8(4): 201. https://doi.org/10.3390/pathogens8040201

Fouque F, Reeder JC (2019) Impact of past and on-going changes on climate and weather on vector-borne diseases transmission: a look at the evidence. Infect Dis Poverty 8(1): 51. https://doi.org/10.1186/s40249-019-0565-1

Frézard F, Demicheli C, Ribeiro RR (2009) Pentavalent antimonials: New perspectives for old drugs. Molecules 14(7): 2317–2336. https://doi.org/10.3390/molecules14072317

Garcia CC, Talarico L, Almeida N, Colombres S, Duschatzky C, Damonte EB (2003) Virucidal activity of essential oils from aromatic plants of San Luis, Argentina. Phytother Res 17(9): 1073–1075. https://doi.org/10.1002/ptr.1305

Garcia MCF, Soares DC, Santana RC, Saraiva EM, Siani AC, Ramos MFS, Danelli M, Souto-Padron TC, Pinto-da-Silva LH (2018) The in vitro antileishmanial activity of essential oil from Aloysia gratissima and guaiol, its major sesquiterpene against Leishmania amazonensis. Parasitology 145(9): 1219–1227. https://doi.org/10.1017/S0031182017002335

Ghadimi SN, Sharifi N, Osanloo M (2020) The leishmanicidal activity of essential oils: A systematic review. J Herbmed Pharmacol 9(4): 300–308. https://doi.org/10.34172/jhp.2020.38

Giraldo Escobar AF (2022) Revisión sistemática de los factores agronómicos del cultivo de Cannabis sativa L. y su relación con sus potenciales usos. Tesis. Escuela de Ciencias Básicas y Aplicadas, Universidad de La Salle, Bogotá.

Goretty M, Ferreira P, Kayano A, Silva-Jardim I, Silva T, Zuliani J, Facundo V, Calderon L, Calderon A, De A, Ciancaglini P, Stabeli R (2010) Antileishmanial activity of 3-(3,4,5-trimethoxyphenyl) propanoic acid purified from Amazonian Piper tuberculatum Jacq., Piperaceae, fruits. Rev Bras Farmacogn 20(6):1003–1006. https://doi.org/10.1590/S0102-695X2010005000033

Guerra JA, Prestes SR, Silveira H, Coelho LI, Gama P, Moura A, Amato V, Barbosa M, Ferreira LC (2011) Mucosal leishmaniasis caused by Leishmania (Viannia) braziliensis and Leishmania (Viannia) guyanensis in the Brazilian Amazon. PLoS Negl Trop Dis 5(3): e980. https://doi.org/10.1371/journal.pntd.0000980

Hajaji S, Sifaoui I, Lopez-Arencibia A, Reyes-Batlle M, Jimenez IA, Bazzocchi IL, Valladares B, Akkari H, Lorenzo-Morales J, Pinero JE (2018) Leishmanicidal activity of alpha-bisabolol from Tunisian chamomile essential oil. Parasitol Res 117(9): 2855–2867. https://doi.org/10.1007/s00436-018-5975-7

Herrera Acevedo C, Scotti L, Feitosa Alves M, Formiga Melo Diniz MF, Scotti MT (2017) Computer-aided drug design using sesquiterpene lactones as sources of new structures with potential activity against infectious neglected diseases. Molecules 22(1): 79–98. https://doi.org/10.3390/molecules22010079

Herrera-Acevedo C, Perdomo-Madrigal C, Muratov EN, Scotti L, Scotti MT (2021) Discovery of alternative chemotherapy options for leishmaniasis through computational studies of Asteraceae. ChemMedChem 16(8): 1234–1245. https://doi.org/10.1002/cmdc.202000862

Higuita-Castro J, Vélez ID, Escobar DM, Murillo J, Pineda T, Ospina V, Robledo SM (2021) Development of a biocompatible polymeric chitosan system for the release of compounds with leishmanicidal activity. Mater Des 212: 110232. https://doi.org/10.1016/j.matdes.2021.110232

Höfling JF, Anibal PC, Obando-Pereda GA, Peixoto IAT, Furletti VF, Foglio MA, Gonçalves RB (2010) Antimicrobial potential of some plant extracts against Candida species. Braz J Biol 70 (4):1065–1068. https://doi.org/10.1590/S1519-69842010000500022

Inacio JD, Canto-Cavalheiro MM, Almeida-Amaral EE (2013) In vitro and in vivo effects of (-)-epigallocatechin 3-O-gallate on Leishmania amazonensis. J Nat Prod 76(10): 1993–1996. https://doi.org/10.1021/np400624d

Ioset J-R (2008) Natural products for neglected diseases: A review. Curr Org Chem 12(8): 643–666. https://doi.org/10.2174/138527208784577394

Jamalian A, Shams-Ghahfarokhi M, Jaimand K, Pashootan N, Amani A, Razzaghi-Abyaneh M (2012) Chemical composition and antifungal activity of Matricaria recutita flower essential oil against medically important dermatophytes and soil-borne pathogens. J Mycol Med 22(4): 308–315. https://doi.org/10.1016/j.mycmed.2012.09.003

Jha P, Bhalerao S, Dhole M (2018) A comparative analysis of anxiolytic activity of Arnica montana and alprazolam in rats using open field test. Int J Basic Clin Pharmacol 7(4): 718–722. https://doi.org/10.18203/2319-2003.ijbcp20181175

Johnson EL, Schmidt WF, Norman HA (1997) Leaf flavonoids as chemotaxonomic markers for two Erythroxylum. Taxa. Z Naturforsch C 52(9-10): 577–585. https://doi.org/10.1515/znc-1997-9-1004

Kato H, Gomez EA, Cáceres AG, Uezato H, Mimori T, Hashiguchi Y (2010) Molecular epidemiology for vector research on leishmaniasis. Int J Environ Res Public Health 7(3): 814–826. https://doi.org/10.3390/ijerph7030814

Kato H, Gomez EA, Seki C, Furumoto H, Martini-Robles L, Muzzio J, Calvopiña M, Velez L, Kubo M, Tabbabi A, Yamamoto DS, Hashiguchi Y (2019) PCR-RFLP analyses of Leishmania species causing cutaneous and mucocutaneous leishmaniasis revealed distribution of genetically complex strains with hybrid and mito-nuclear discordance in Ecuador. PLoS Negl Trop Dis 13(5): e0007403. https://doi.org/10.1371/journal.pntd.0007403

Kawakami MYM, Zamora LO, Araújo RS, Fernandes CP, Ricotta TQN, de Oliveira LG, Queiroz-Junior CM, Fernandes AP, da Conceição EC, Ferreira LAM, Barros ALB, Aguiar MG, Oliveira A (2021) Efficacy of nanoemulsion with Pterodon emarginatus Vogel oleoresin for topical treatment of cutaneous leishmaniasis. Biomed Pharmacother 134: 111109. https://doi.org/10.1016/j.biopha.2020.111109

Kevric I, Cappel MA, Keeling JH (2015) New World and Old World Leishmania infections: A practical review. Dermatol Clin 33(3): 579–593. https://doi.org/10.1016/j.det.2015.03.018

Klaas CA, Wagner G, Laufer S, Sosa S, Della Loggia R, Bomme U, Pahl HL, Merfort I (2002) Studies on the anti-inflammatory activity of phytopharmaceuticals prepared from Arnica flowers. Planta Med 68(5): 385–391. https://doi.org/10.1055/s-2002-32067

Klatt S, Simpson L, Maslov DA, Konthur Z (2019) Leishmania tarentolae: Taxonomic classification and its application as a promising biotechnological expression host. PLoS Negl Trop Dis 13(7): e0007424. https://doi.org/10.1371/journal.pntd.0007424

Koutsoni OS, Karampetsou K, Dotsika E (2019) In vitro screening of antileishmanial activity of natural product compounds: Determination of IC(50), CC(50) and SI values. Bio Protoc 9(21): e3410. https://doi.org/10.21769/BioProtoc.3410

Kriplani P, Guarve K, Baghael US (2017) Arnica montana L. – A plant of healing: review. J Pharm Pharmacol 69(8): 925–945. https://doi.org/10.1111/jphp.12724

Lima J, Belem Pinheiro M, Santos A, Pereira J, Santos D, Barison A, Silva-Jardim I, Costa E (2012) In vitro antileishmanial and cytotoxic activities of Annona mucosa (Annonaceae). Rev Virtual Quim 4(6): 692–702. https://doi.org/10.5935/1984-6835.20120052

Liu K, Abdullah AA, Huang M, Nishioka T, Altaf-Ul-Amin M, Kanaya S (2017) Novel approach to classify plants based on metabolite-content similarity. BioMed Res Int 2017: 12. https://doi.org/10.1155/2017/5296729

Llanos-Cuentas A, Tulliano G, Araujo-Castillo R, Miranda-Verastegui C, Santamaria-Castrellon G, Ramirez L, Lazo M, De Doncker S, Boelaert M, Robays J, Dujardin JC, Arevalo J, Chappuis F (2008) Clinical and parasite species risk factors for pentavalent antimonial treatment failure in cutaneous leishmaniasis in Peru. Clin Infect Dis 46(2): 223–231. https://doi.org/10.1086/524042

Lozano YY, Giraldo SE, Castro HS, Sánchez RM (2022) Plantas medicinales con potencial actividad neuroprotectora estudiadas en cepas transgénicas de Caenorhabditis elegans. J Pharm Pharmacogn Res 10(5): 812–836. https://doi.org/10.56499/jppres22.1379_10.5.812

Lucas CM, Franke ED, Cachay MI, Tejada A, Cruz ME, Kreutzer RD, Barker DC, McCann SH, Watts DM (1998) Geographic distribution and clinical description of leishmaniasis cases in Peru. Am J Trop Med Hyg 59(2): 312–317. https://doi.org/10.4269/ajtmh.1998.59.312

Luize PS, Tiuman TS, Morello LG, Maza PK, Ueda-Nakamura T, Dias Filho BP, Cortez DAG, De Mello JCP, Nakamura CV (2005) Effects of medicinal plant extracts on growth of Leishmania (L.) amazonensis and Trypanosoma cruzi. Rev Bras Cienc Farm 41(1): 85–94. https://doi.org/10.1590/S1516-93322005000100010

Macêdo CG, Fonseca MYN, Caldeira AD, Castro SP, Pacienza-Lima W, Borsodi MPG, Sartoratto A, da Silva MN, Salgado CG, Rossi-Bergmann B, Castro KCF (2020) Leishmanicidal activity of Piper marginatum Jacq. from Santarém-PA against Leishmania amazonensis. Exp Parasitol 210: 107847. https://doi.org/10.1016/j.exppara.2020.107847

Machado M, Santoro G, Sousa MC, Salgueiro L, Cavaleiro C (2010) Activity of essential oils on the growth of Leishmania infantum promastigotes 25(3): 156–160. https://doi.org/10.1002/ffj.1987

Machado R, Júnior W, Lesche B, Coimbra E, Bellotti de Souza N, Abramo C, Soares G, Kaplan M (2012) Essential oil from leaves of Lantana camara: A potential source of medicine against leishmaniasis. Rev Bras Farmacogn 22(5): 1011–1017. https://doi.org/10.1590/S0102-695X2012005000057

Majid Shah S, Ullah F, Ayaz M, Sadiq A, Hussain S, Ali Shah A-u-H, Adnan Ali Shah S, Wadood A, Nadhman A (2019) β-Sitosterol from Ifloga spicata (Forssk.) Sch. Bip. as potential anti-leishmanial agent against Leishmania tropica: Docking and molecular insights. Steroids 148: 56–62. https://doi.org/10.3390/pr7040208

Mann S, Frasca K, Scherrer S, Henao-Martínez AF, Newman S, Ramanan P, Suarez JA (2021) A review of leishmaniasis: Current knowledge and future directions. Curr Trop Med Rep 8(2): 121–132. https://doi.org/10.1007/s40475-021-00232-7

Manta B, Comini M, Medeiros A, Hugo M, Trujillo M, Radi R (2013) Trypanothione: A unique bis-glutathionyl derivative in trypanosomatids. Biochim Biophys Acta 1830(5): 3199–3216. https://10.1016/j.bbagen.2013.01.013

Marcondes M, Day MJ (2019) Current status and management of canine leishmaniasis in Latin America. Res Vet Sci 123: 261–272. https://doi.org/10.1016/j.rvsc.2019.01.022

Marlow MA, da Silva Mattos M, Makowiecky ME, Eger I, Rossetto AL, Grisard EC, Steindel M (2013) Divergent profile of emerging cutaneous leishmaniasis in subtropical Brazil: New endemic areas in the southern frontier. PLoS One 8(2): e56177. https://doi.org/10.1371/journal.pone.0056177

Mat Sharil AT, Basma Ezzat M, Widya L, Amri Nurhakim MH, Nor Hikmah AR, Nabilah Zafira Z, Haris MS (2022) Systematic review of flaxseed (Linum usitatissimum L.) extract and formulation in wound healing. J Pharm Pharmacogn Res 10(1): 1–12. https://doi.org/10.56499/jppres21.1125_10.1.1

Matias JN, Achete de Souza G, Kumar Joshi R, Vaz de Marqui S, Landgraf Guiguer É, Cressoni Araújo A, Machado Bueno Otoboni AM, Marineli P, Barbalho SM (2021) Arrabidaea chica (Humb. and Bonpl.): A plant with multipurpose medicinal applications. Int J Herbal Med 9(1): 77–86.

Matos FJA, Machado MIL, Alencar JW, Craveiro AA (1993) Constituents of Brazilian chamomile oil. J Essent Oil Res 5(3): 337–339. https://doi.org/10.1080/10412905.1993.9698234

Mayaud L, Carricajo A, Zhiri A, Aubert G (2008) Comparison of bacteriostatic and bactericidal activity of 13 essential oils against strains with varying sensitivity to antibiotics. Lett Appl Microbiol 47(3): 167–173. https://doi.org/10.1111/j.1472-765X.2008.02406.x

McInnes MDF, Moher D, Thombs BD, McGrath TA, Bossuyt PM, Clifford T, Cohen JF, Deeks JJ, Gatsonis C, Hooft L, Hunt HA, Hyde CJ, Korevaar DA, Leeflang MMG, Macaskill P, Reitsma JB, Rodin R, Rutjes AWS, Salameh JP, Stevens A, Takwoingi Y, Tonelli M, Weeks L, Whiting P, Willis BH (2018) Preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies: The PRISMA-DTA statement. JAMA 319(4): 388–396. https://10.1001/jama.2017.19163

McKay DL, Blumberg JB (2006) A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.). Phytother Res 20(7): 519–530. https://doi.org/10.1002/ptr.1900

Ministério da Saúde (2022) Plantas Medicinais de Interesse ao SUS – Renisus — Português (Brasil). in: M. d. Saúde (Ed.), Brasil. https://www.gov.br/saude/pt-br/composicao/sectics/daf/pnpmf/ppnpmf/renisus

Misra P, Kumar A, Khare P, Gupta S, Kumar N, Dube A (2009) Pro-apoptotic effect of the landrace Bangla Mahoba of Piper betle on Leishmania donovani may be due to the high content of eugenol. J Med Microbiol 58(Pt 8): 1058–1066. https://doi.org/10.1099/jmm.0.009290-0

Moghaddam M, Mehdizadeh L (2017) Chapter 13 – Chemistry of Essential Oils and Factors Influencing Their Constituents. In: Grumezescu AM and Holban AM (eds.), Soft Chemistry and Food Fermentation, Academic Press. pp. 379–419. https://doi.org/10.1016/B978-0-12-811412-4.00013-8

Monção NB, Costa LM, Arcanjo DD, Araújo BQ, Lustosa Mdo C, Rodrigues KA, Carvalho FA, Costa AP, Lopes Citó AM (2014) Chemical constituents and toxicological studies of leaves from Mimosa caesalpiniifolia Benth., a Brazilian honey plant. Pharmacogn Mag 10(Suppl 3): S456–462. https://doi.org/10.4103/0973-1296.139773

Montrieux E, Perera WH, García M, Maes L, Cos P, Monzote L (2014) In vitro and in vivo activity of major constituents from Pluchea carolinensis against Leishmania amazonensis. Parasitol Res 113(8): 2925–2932. https://doi.org/10.1007/s00436-014-3954-1

Monzote L, García M, Pastor J, Gil L, Scull R, Maes L, Cos P, Gille L (2014) Essential oil from Chenopodium ambrosioides and main components: activity against Leishmania, their mitochondria and other microorganisms. Exp Parasitol 136: 20–26. https://doi.org/10.1016/j.exppara.2013.10.007

Monzote L, Herrera I, Satyal P, Setzer WN (2019) In-vitro evaluation of 52 commercially-available essential oils against Leishmania amazonensis. Molecules 24(7): 1248. https://doi.org/10.3390/molecules24071248

Monzote L, Montalvo AM, Almanonni S, Scull R, Miranda M, Abreu J (2006) Activity of the essential oil from Chenopodium ambrosioides grown in Cuba against Leishmania amazonensis. Chemotherapy 52(3): 130–136. https://doi.org/10.1159/000092858

Moraes Neto RN, Setúbal RFB, Higino TMM, Brelaz-de-Castro MCA, da Silva LCN, Aliança A (2019) Asteraceae plants as sources of compounds against Leishmaniasis and Chagas disease. Front Pharmacol 10: 477. https://doi.org/10.3389/fphar.2019.00477

Mororó GT, de Oliveira Ferreira JR, de Morais Alves MM, Nery Monção NB, de Carvalho-Gonçalves LCT, Graças Lopes Citó AMd, Pinheiro Ferreira PM, de Amorim Carvalho FA, Ramos Gonçalves JC (2018) Study of the antileukemic activity of Mimosa caesalpiniifolia Benth. ethanolic extract and fractions. J Trend Phytochem Res 2(3): 127–134. https://tpr.shahrood.iau.ir/article_543322.html

Nakamura C, Santos A, Vendrametto M, Luize P, Filho B, Cortez D, Ueda-Nakamura T (2006) Antileishmanial activity of hydroalcoholic extract and fractions obtained from leaves of Piper regnellii (Miq.) C. DC. var. pallescens (C. DC.). Rev Bras Farmacogn 16: 61–66. https://doi.org/10.1590/S0102-695X2006000100011

Nissen L, Zatta A, Stefanini I, Grandi S, Sgorbati B, Biavati B, Monti A (2010) Characterization and antimicrobial activity of essential oils of industrial hemp varieties (Cannabis sativa L.). Fitoterapia 81(5): 413–419. https://doi.org/10.1016/j.fitote.2009.11.010

Nogueira RC, Rocha VP, Nonato FR, Tomassini TC, Ribeiro IM, dos Santos RR, Soares MB (2013) Genotoxicity and antileishmanial activity evaluation of Physalis angulata concentrated ethanolic extract. Environ Toxicol Pharmacol 36(3): 1304–1311. https://doi.org/10.1016/j.etap.2013.10.013

Nok AJ, Ibrahim S, Arowosafe S, Longdet I, Ambrose A, Onyenekwe PC, Whong CZ (1994) The trypanocidal effect of Cannabis sativa constituents in experimental animal trypanosomiasis. Vet Hum Toxicol 36(6): 522–524. https://pubmed.ncbi.nlm.nih.gov/7900270/

Nunes TAL, Costa LH, De Sousa JMS, De Souza VMR, Rodrigues RRL, Val M, Pereira A, Ferreira GP, Da Silva MV, Da Costa J, Veras LMC, Diniz RC, Rodrigues K (2021) Eugenia piauhiensis Vellaff. essential oil and gamma-elemene its major constituent exhibit antileishmanial activity, promoting cell membrane damage and in vitro immunomodulation. Chem Biol Interact 339: 109429. https://doi.org/10.1016/j.cbi.2021.109429

Obón C, Rivera D, Verde A, Fajardo J, Valdés A, Alcaraz F, Carvalho AM (2012) Arnica: A multivariate analysis of the botany and ethnopharmacology of a medicinal plant complex in the Iberian Peninsula and the Balearic Islands. J Ethnopharmacol 144(1): 44–56. https://doi.org/10.1016/j.jep.2012.08.024

Ocazionez RE, Meneses R, Torres FA, Stashenko E (2010) Virucidal activity of Colombian Lippia essential oils on dengue virus replication in vitro. Mem Inst Oswaldo Cruz 105(3): 304–309. https://doi.org/10.1590/s0074-02762010000300010

Odonne G, Herbette G, Eparvier V, Bourdy G, Rojas R, Sauvain M, Stien D (2011) Antileishmanial sesquiterpene lactones from Pseudelephantopus spicatus, a traditional remedy from the Chayahuita Amerindians (Peru). Part III. J Ethnopharmacol 137(1): 875–879. https://doi.org/10.1016/j.jep.2011.07.008

Oliveira FAS, Passarini GM, Medeiros DSS, Santos APA, Fialho SN, Gouveia AJ, Latorre M, Freitag EM, Medeiros PSM, Teles CBG, Facundo VA (2018) Antiplasmodial and antileishmanial activities of compounds from Piper tuberculatum Jacq fruits. Rev Soc Bras Med Trop 51(3): 382–386. https://doi.org/10.1590/0037-8682-0309-2017

Oryan A (2015). Plant-derived compounds in treatment of leishmaniasis. Iran J Vet Res 16(1): 1–19. https://pubmed.ncbi.nlm.nih.gov/27175144

Paduch R, Kandefer-Szerszeń M, Trytek M, Fiedurek J (2007) Terpenes: substances useful in human healthcare. Arch Immunol Ther Exp 55(5): 315–327. https://doi.org/10.1007/s00005-007-0039-1

Pan American Health Organization (PAHO) – OPS/OMS (2017) Plan de acción para fortalecer la vigilancia y control de las leishmaniasis en las Américas 2017-2022, in: D. d. E. T. y. A. d. Salud (Ed.). https://iris.paho.org/handle/10665.2/34144

Pan American Health Organization (PAHO) – OPS/OMS (2022) Leishmaniasis. https://www.paho.org/en/topics/leishmaniasis (accessed 16 April 2023).

Peixoto JF, Ramos YJ, de Lima Moreira D, Alves CR, Gonçalves-Oliveira LF (2021) Potential of Piper spp. as a source of new compounds for the leishmaniases treatment. Parasitol Res 120(8): 2731-2747. https://doi.org/10.1007/s00436-021-07199-4

Pérez S, Ramos-Lopez M, Sánchez-Miranda E, Fresán-Orozco M, Pérez-Ramos J (2012) Antiprotozoa activity of some essential oils. J Med Plant Res 6(15): 2901–2908. https://doi.org/10.5897/JMPR11.1572

Pérez-Loyola M, Valdés-González M, Garrido G (2022) Modified pectins with activity against colon cancer: A systematic review from 2010-2021. J Pharm Pharmacogn Res 10(4): 616–651. https://doi.org/10.56499/jppres22.1387.10.4.616

Perigo CV, Torres RB, Bernacci LC, Guimarães EF, Haber LL, Facanali R, Vieira MAR, Quecini V, Marques MOM (2016) The chemical composition and antibacterial activity of eleven Piper species from distinct rainforest areas in Southeastern Brazil. Ind Crops Prod 94: 528–539. https://doi.org/10.1016/j.indcrop.2016.09.028

Pires M, Wright B, Kaye PM, da Conceição V, Churchill RC (2019) The impact of leishmaniasis on mental health and psychosocial well-being: A systematic review. PLoS One 14(10): e0223313. https://doi.org/10.1371/journal.pone.0223313

Ponte-Sucre A, Gamarro F, Dujardin JC, Barrett MP, López-Vélez R, García-Hernández R, Pountain AW, Mwenechanya R, Papadopoulou B (2017) Drug resistance and treatment failure in leishmaniasis: A 21st century challenge. PLoS Negl Trop Dis 11(12): e0006052. https://doi.org/10.1371/journal.pntd.0006052

POWO (2022) Piper marginatum Jacq. Plants of the World Online. Royal Botanic Gardens, Kew. https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:682138-1 (Consulted 16 April 2023).

Pramanik PK, Chakraborti S, Bagchi A, Chakraborti T (2020) Bioassay-based Corchorus capsularis L. leaf-derived β-sitosterol exerts antileishmanial effects against Leishmania donovani by targeting trypanothione reductase. Sci Rep 10(1): 20440. https://doi.org/10.1038/s41598-020-77066-2

Qaid MAN, Algabr MN, Khamis AO, Wang H (2017) Anticancer, antimicrobial and antioxidant activities of the essential oils of some aromatic medicinal plants (Pulicaria inuloides-Asteraceae). J Food Nutr Res 5(7): 490–495. https://10.12691/jfnr-5-7-6

Quirino Araújo B, Monção N, Oliveira L, Santana L, Arcanjo D, Rodrigues K, Carvalho F, Citó AMGL (2020) 3-O-Acyl triterpenoids and antileishmanial effect of the ethanolic extract from Mimosa caesalpiniifolia inflorescences. Curr Bioact Compd 16(8): 1225–1230. http://dx.doi.org/10.2174/2212796814666200124120712

Radwan MM, Elsohly MA, Slade D, Ahmed SA, Khan IA, Ross SA (2009) Biologically active cannabinoids from high-potency Cannabis sativa. J Nat Prod 72(5): 906–911. https://doi.org/10.1021/np900067k

Radwan MM, Ross SA, Slade D, Ahmed SA, Zulfiqar F, Elsohly MA (2008) Isolation and characterization of new Cannabis constituents from a high potency variety. Planta Med 74(3): 267–272. https://doi.org/10.1055/s-2008-1034311

Raimundo VD, Carvalho RPR, Machado-Neves M, Marques-da-Silva EA (2022) Effects of terpenes in the treatment of visceral leishmaniasis: A systematic review of preclinical evidence. Pharmacol Res 177: 106117. https://doi.org/10.1016/j.phrs.2022.106117

Ramalho Carvalho PE (2007) Sabiá – Mimosa caesalpiniifolia. In: Florestas CE (ed.), Brasil. pp. 10.

Reichling J, Koch C, Stahl-Biskup E, Sojka C, Schnitzler P (2005) Virucidal activity of a beta-triketone-rich essential oil of Leptospermum scoparium (manuka oil) against HSV-1 and HSV-2 in cell culture. Planta Med 71(12): 1123–1127. https://doi.org/10.1055/s-2005-873175

Reichling J, Schnitzler P, Suschke U, Saller R (2009) Essential oils of aromatic plants with antibacterial, antifungal, antiviral, and cytotoxic properties – An overview. Forsch Komplementmed 16(2): 79–90. https://doi.org/10.1159/000207196

Rhayour K, Bouchikhi T, Tantaoui-Elaraki A, Sendide K, Remmal A (2003) The mechanism of bactericidal action of oregano and clove essential oils and of their phenolic major components on Escherichia coli and Bacillus subtilis. J Essent Oil Res 15(5): 356–362. https://doi.org/10.1080/10412905.2003.9698611

Ribeiro N, Camara C, Ramos C (2016) Toxicity of essential oils of Piper marginatum Jacq. against Tetranychus urticae Koch and Neoseiulus californicus (McGregor). Chilean J Agric Res 76: 71–76. http://dx.doi.org/10.4067/S0718-58392016000100010

Ribeiro TG, Chávez-Fumagalli MA, Valadares DG, Franca JR, Lage PS, Duarte MC, Andrade PH, Martins VT, Costa LE, Arruda AL, Faraco AA, Coelho EA, Castilho RO (2014) Antileishmanial activity and cytotoxicity of Brazilian plants. Exp Parasitol 143: 60–68. https://doi.org/10.1016/j.exppara.2014.05.004

Rizk YS, Fischer A, Cunha MdC, Rodrigues PO, Marques MC, Matos MdF, Kadri MC, Carollo CA, Arruda CC (2014) In vitro activity of the hydroethanolic extract and biflavonoids isolated from Selaginella sellowii on Leishmania (Leishmania) amazonensis. Mem Inst Oswaldo Cruz 109(8): 1050–1056. https://doi.org/10.1590/0074-0276140312

Robledo S, Restrepo A, Yepes L, Fernández M, Vélez I (2017) Studies in vitro and in vivo of antileishmanial activity and differential cytotoxicity of Cannabis spp. Plant Med Int Open 4(S 01): S1–S202. https://doi.org/10.1055/s-0037-1608170

Robledo SM, Murillo J, Arbeláez N, Montoya A, Ospina V, Jürgens FM, Vélez ID, Schmidt TJ (2022) Therapeutic efficacy of Arnica in hamsters with cutaneous leishmaniasis caused by Leishmania braziliensis and L. tropica. Pharmaceuticals (Basel) 15(7): 776. https://doi.org/10.3390/ph15070776

Roby MHH, Sarhan MA, Selim KA-H, Khalel KI (2013) Antioxidant and antimicrobial activities of essential oil and extracts of fennel (Foeniculum vulgare L.) and chamomile (Matricaria chamomilla L.). Ind Crops Prod 44: 437–445. https://doi.org/10.1016/j.indcrop.2012.10.012

Rocha VPC, Quintino da Rocha C, Ferreira Queiroz E, Marcourt L, Vilegas W, Grimaldi GB, Furrer P, Allémann É, Wolfender JL, Soares MBP (2018) Antileishmanial activity of dimeric flavonoids isolated from Arrabidaea brachypoda. Molecules 24(1): 1. https://doi.org/10.3390/molecules24010001

Rodrigues de Moraes PL (2007) Taxonomy of Cryptocarya species of Brazil. Belgian Development Cooperation 3:199.

Rodrigues IA, Azevedo MM, Chaves FC, Alviano CS, Alviano DS, Vermelho AB (2014) Arrabidaea chica hexanic extract induces mitochondrion damage and peptidase inhibition on Leishmania spp. Biomed Res Int 2014: 985171. https://doi.org/10.1155/2014/985171

Rodrigues KA, Amorim LV, de Oliveira JM, Dias CN, Moraes DF, Andrade EH, Maia JG, Carneiro SM, Carvalho FA (2013) Eugenia uniflora L. essential oil as a potential anti-leishmania agent: Effects on Leishmania amazonensis and possible mechanisms of action. Evid Based Complement Alternat Med 2013: 279726. https://doi.org/10.1155/2013/279726

Rodrigues-Silva D, Nakamura CV, Dias Filho BP, Ueda-Nakamura T, Ranieri-Cortez D, Cortez D (2009) In vitro Antileishmanial Activity of Hydroalcoholic Extract, Fractions, and Compounds Isolated from Leaves of Piper ovatum Vahl against Leishmania amazonensis. Planta Med 75: PD29. https://doi.org/10.1055/s-0029-1234508

Rodríguez-Chaves D, Bagnarello-Madrigal V, Alpizar-Cordero J, Calvo-Vargas A, Cordero-Villalobos M, Chinchilla-Carmona M, Valerio-Campos I, Sánchez Porras R (2018) Actividad in vitro anti-Leishmania (Trypanosomatidae) del epóxido trans-Z-α-bisaboleno y del safrol, en frutos de Piper auritum (Piperaceae). Rev Biol Trop 66(2): 826–835. http://dx.doi.org/10.15517/rbt.v66i2.33412

Romero GA, Vinitius De Farias Guerra M, Gomes Paes M, de Oliveira Macêdo V (2001) Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in Brazil: Clinical findings and diagnostic approach. Clin Infect Dis 32(9): 1304–1312. https://doi.org/10.1086/319990

Rottini MM, Amaral AC, Ferreira JL, Silva JR, Taniwaki NN, Souza Cda S, d’Escoffier LN, Almeida-Souza F, Hardoim DdJ, Gonçalves da Costa SC, Calabrese KdS (2015) In vitro evaluation of (-) α-bisabolol as a promising agent against Leishmania amazonensis. Exp Parasitol 148: 66–72. https://doi.org/10.1016/j.exppara.2014.10.001

Russo EB (2007) History of cannabis and its preparations in saga, science, and sobriquet. Chem Biodivers 4(8): 1614–1648. https://doi.org/10.1002/cbdv.200790144

Salgado-Almario J, Hernández CA, Ovalle CE (2019) Geographical distribution of Leishmania species in Colombia, 1985-2017. Biomedica 39(2): 278–290. https://doi.org/10.7705/biomedica.v39i3.4312

Sánchez Y, Correa TM, Abreu Y, Martínez B, Duarte Y, Pino O (2011) Caracterización química y actividad antimicrobiana del aceite esencial de Piper marginatum Jacq. Rev Prot Veg 26(3):170–176.

Santin MR, dos Santos AO, Nakamura CV, Dias Filho BP, Ferreira IC, Ueda-Nakamura T (2009) In vitro activity of the essential oil of Cymbopogon citratus and its major component (citral) on Leishmania amazonensis. Parasitol Res 105(6): 1489–1496. https://doi.org/10.1007/s00436-009-1578-7

Santos ME, Moura LH, Mendes MB, Arcanjo DD, Monção NB, Araújo BQ, Lopes JA, Silva-Filho JC, Fernandes RM, Oliveira RC, Citó AM, Oliveira AP (2015) Hypotensive and vasorelaxant effects induced by the ethanolic extract of the Mimosa caesalpiniifolia Benth. (Mimosaceae) inflorescences in normotensive rats. J Ethnopharmacol 164: 120–128. https://doi.org/10.1016/j.jep.2015.02.008

Saravia NG, Holguín AF, McMahon-Pratt D, D’Alessandro A (1985) Mucocutaneous leishmaniasis in Colombia: Leishmania braziliensis subspecies diversity. Am J Trop Med Hyg 34(4): 714–720. https://doi.org/10.4269/ajtmh.1985.34.714

Schmeda-Hirschmann G, Razmilic I, Sauvain M, Moretti C, Muñoz V, Ruiz E, Balanza E, Fournet A (1996) Antiprotozoal activity of jatrogrossidione from Jatropha grossidentata and jatrophone from Jatropha isabellii. Phytother Res 10(5): 375–378. https://doi.org/10.1002/(SICI)1099-1573(199608)10:5%3C375::AID-PTR847%3E3.0.CO;2-%23

Schmidt TJ, Nour AM, Khalid SA, Kaiser M, Brun R (2009) Quantitative structure–antiprotozoal activity relationships of sesquiterpene lactones. Molecules 14(6): 2062–2076. https://doi.org/10.3390/molecules14062062

Sikkema J, de Bont JA, Poolman B (1995) Mechanisms of membrane toxicity of hydrocarbons. Microbiol Rev 59(2): 201–222. https://doi.org/10.1128/mr.59.2.201-222.1995

Silva L, Araújo A, Dutra V (2022) Flora of Espírito Santo: Mimosa (Leguminosae: Caesalpinioideae: mimosoid clade). Rodriguésia 73: 24. https://doi.org/10.1590/2175-7860202273005

Silva MJd, Endo LH, Dias ALT, Silva GAd, Santos MHd (2012) Avaliacáo da atividade antioxidante e antimicrobiana dos extratos e fracoes orgánicas de Mimosa caesalpiniifolia Benth. (Mimosaceae). Rev de Ciênc Farm Básica Apl 33(2): 267–274.

Silva-Silva JV, Moragas-Tellis CJ, Chagas MSS, Souza PVR, Moreira DL, de Souza CSF, Teixeira KF, Cenci AR, de Oliveira AS, Almeida-Souza F, Behrens MD, Calabrese KS (2021) Carajurin: A anthocyanidin from Arrabidaea chica as a potential biological marker of antileishmanial activity. Biomed Pharmacother 141: 111910. https://doi.org/10.1016/j.biopha.2021.111910

Singh O, Khanam Z, Misra N, Srivastava MK (2011) Chamomile (Matricaria chamomilla L.): An overview. Pharmacogn Rev 5(9): 82–95. https://doi.org/10.4103/0973-7847.79103

Siqueira C, Oliani J, Sartoratto A, Queiroga C, Moreno P, Reimão J, Tempone A, Fischer D (2011) Chemical constituents of the volatile oil from leaves of Annona coriacea and in vitro antiprotozoal activity. Rev Bras Farmacogn 21(1): 33–40. https://doi.org/10.1590/S0102-695X2011005000004

Siraichi JT, Felipe DF, Brambilla LZ, Gatto MJ, Terra VA, Cecchini AL, Cortez LE, Rodrigues-Filho E, Cortez DA (2013) Antioxidant capacity of the leaf extract obtained from Arrabidaea chica cultivated in Southern Brazil. PLoS One 8(8): e72733. https://doi.org/10.1371/journal.pone.0072733

Sitara U, Niaz I, Naseem J, Sultana N (2008) Antifungal effect of essential oils on in vitro growth of pathogenic fungi. Pak J Bot 40(1): 409–414.

Sosa AM, Amaya S, Salamanca Capusiri E, Gilabert M, Bardón A, Giménez A, Vera NR, Borkosky SA (2016) Active sesquiterpene lactones against Leishmania amazonensis and Leishmania braziliensis. Nat Prod Res 30(22): 2611–2615. https://doi.org/10.1080/14786419.2015.1126260

Sousa Júnior JR, Albuquerque UP, Peroni N (2013) Traditional knowledge and management of Caryocar coriaceum Wittm. (Pequi) in the Brazilian Savanna, Northeastern Brazil. Econ Bot 67(3): 225–233. https://doi.org/10.1007/s12231-013-9241-8

Souza AA, Wiest JM (2007) Atividade antibacteriana de Aloysia gratissima (Gill et Hook) Tronc. (garupá, erva-santa) usada na medicina tradicional no Rio Grande do Sul-Brasil. Rev Bras Pl Med 9(3): 23–29.

Sülsen VP, Frank FM, Cazorla SI, Anesini CA, Malchiodi EL, Freixa B, Vila R, Muschietti LV, Martino VS (2008) Trypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae). Antimicrob Agents Chemother 52(7): 2415–2419. https://doi.org/10.1128/aac.01630-07

Thiem DA, Sneden AT, Khan SI, Tekwani BL (2005) Bisnortriterpenes from Salacia madagascariensis. J Nat Prod 68(2): 251–254. https://doi.org/10.1021/np0497088

Tiuman TS, Ueda-Nakamura T, Garcia Cortez DA, Dias Filho BP, Morgado-Díaz JA, de Souza W, Nakamura CV (2005) Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium. Antimicrob Agents Chemother 49(1): 176–182. https://doi.org/10.1128/aac.49.11.176-182.2005

Tomiotto-Pellissier F, Alves DR, Miranda-Sapla MM, de Morais SM, Assolini JP, da Silva Bortoleti BT, Gonçalves MD, Cataneo AHD, Kian D, Madeira TB, Yamauchi LM, Nixdorf SL, Costa IN, Conchon-Costa I, Pavanelli WR (2018) Caryocar coriaceum extracts exert leishmanicidal effect acting in promastigote forms by apoptosis-like mechanism and intracellular amastigotes by Nrf2/HO-1/ferritin dependent response and iron depletion: Leishmanicidal effect of Caryocar coriaceum leaf exracts. Biomed Pharmacother 98: 662–672. https://doi.org/10.1016/j.biopha.2017.12.083

Torres-Santos EC, Moreira DL, Kaplan MA, Meirelles MN, Rossi-Bergmann B (1999) Selective effect of 2′,6′-dihydroxy-4′-methoxychalcone isolated from Piper aduncum on Leishmania amazonensis. Antimicrob Agents Chemother 43(5): 1234–1241. https://doi.org/10.1128/aac.43.5.1234

Trovati G, Chierice GO, Sanches EA, Galhiane MS (2009) Essential oil composition of Aloysia gratissima from Brazil. J Essent Oil Res 21(4): 325–326. https://doi.org/10.1080/10412905.2009.9700183

Uliana SRB, Trinconi CT, Coelho AC (2018) Chemotherapy of leishmaniasis: Present challenges. Parasitology 145(4): 464–480. https://doi.org/10.1017/S0031182016002523

Vargas W (2021) First record of the genus Cryptocarya (Lauraceae) for Colombia. Caldasia 43(1): 218–220. https://doi.org/10.15446/caldasia.v43n1.82492

Viola H, Wasowski C, Levi de Stein M, Wolfman C, Silveira R, Dajas F, Medina JH, Paladini AC (1995) Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. Planta Med 61(3): 213–216. https://doi.org/10.1055/s-2006-958058

Waizel-Bucay J, Cruz-Juárez MdL (2014) Arnica montana L., relevant European medicinal plant. Rev Mex Cienc Forestales 5(25): 98–109.

Wamai RG, Kahn J, McGloin J, Ziaggi G (2020) Visceral leishmaniasis: a global overview. J Glob Health Sci 2(1): e3. https://doi.org/10.35500/jghs.2020.2.e3

Weniger B, Robledo S, Arango GJ, Deharo E, Aragón R, Muñoz V, Callapa J, Lobstein A, Anton R (2001) Antiprotozoal activities of Colombian plants. J Ethnopharmacol 78(2–3): 193–200. https://doi.org/10.1016/S0378-8741(01)00346-4

World Health Organization (2021) Leishmaniasis, Status of endemicity. (Accessed 16 April 2023).

World Health Organization (2022) Leishmaniasis. (Accessed 16 April 2023).

Wulsten IF, Costa-Silva TA, Mesquita JT, Lima ML, Galuppo MK, Taniwaki NN, Borborema SET, Da Costa FB, Schmidt TJ, Tempone AG (2017) Investigation of the anti-Leishmania (Leishmania) infantum activity of some natural sesquiterpene lactones. Molecules 22(5): 685. https://doi.org/10.3390/molecules22050685

Youssefi MR, Moghaddas E, Tabari MA, Moghadamnia AA, Hosseini SM, Farash BRH, Ebrahimi MA, Mousavi NN, Fata A, Maggi F, Petrelli R, Dall’Acqua S, Benelli G, Sut S (2019) In vitro and in vivo effectiveness of carvacrol, thymol and linalool against Leishmania infantum. Molecules 24(11): 2072. https://doi.org/10.3390/molecules24112072

Zapata UYA, Echeverri F, Quiñones W, Torres F, Nacher M, Rivas LI, Meira CDS, Gedamu L, Escobar G, Archbold R, Vélez ID, Robledo SM (2020) Mode of action of a formulation containing hydrazones and saponins against leishmania spp. Role in mitochondria, proteases and reinfection process. Int J Parasitol Drugs Drug Resist 13: 94–106. https://doi.org/10.1016/j.ijpddr.2020.06.004

Zeni AL, Zomkowski AD, Dal-Cim T, Maraschin M, Rodrigues AL, Tasca CI (2011) Antidepressant-like and neuroprotective effects of Aloysia gratissima: investigation of involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway. J Ethnopharmacol 137(1): 864–874. https://doi.org/10.1016/j.jep.2011.07.009

Zhao G, Cao Z, Zhang W, Zhao H (2015) The sesquiterpenoids and their chemotaxonomic implications in Senecio L. (Asteraceae). Biochem Syst Ecol 59: 340–347. https://doi.org/10.1016/j.bse.2015.02.001

© 2023 Journal of Pharmacy & Pharmacognosy Research

Coffee-tea-turmeric work in cardiac-metabolic syndrome

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 961-974, Nov-Dec 2023.

DOI: https://doi.org/10.56499/jppres23.1702_11.6.961

Original Article

The analysis of coffee-green tea-turmeric combination against cardiac-metabolic syndrome using metabolite profiling, gene expression, and in silico approach

[Análisis de la combinación de café, té verde y cúrcuma contra el síndrome cardiometabólico mediante perfiles de metabolitos, expresión génica y enfoque in silico]

Ermin Rachmawati1,2*, Mohammad S. Rohman1,3*, Nashi Widodo1,4, Mifetika Lukitasari1,5, Dwi A. Nugroho1, Feri E. Hermanto1,6,7, Mukhamad N. Kholis1,2

1Research Center for Cardiovascular, Brawijaya University, Malang, Indonesia.

2Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, UIN Maulana Malik Ibrahim Malang, East Java, Indonesia.

3Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

4Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia.

5School of Nursing, Faculty of Health Sciences, Universitas Brawijaya, Malang, Indonesia.

6Faculty of Animal Sciences, Universitas Brawijaya, Malang, Indonesia.

7Bioinformatics Research Center, Indonesian Institute of Bioinformatics, Malang, Indonesia.

*E-mail address: ermin.rachmawati@kedokteran.uin-malang.ac.id, ippoenk@ub.ac.id

Abstract

Context: The development of functional drinks to inhibit oxidative stress and inflammation as a critical process in inducing heart damage in metabolic syndrome is required. Coffee, tea, and turmeric have all been shown to offer health advantages.

Aims: To investigate the effect of coffee, green tea, turmeric extract (ECGTT) against cardiac-metabolic syndrome (MetS).

Methods: The secondary metabolites from coffee, green tea, and turmeric were identified using LC-HRMS. Male Sprague–Dawley rats were divided into four groups (n = 4) representing normal, MetS, MetS with ECGTT treatment doses: 300/100/150 mg/BW and 300/100/250 mg/BW group. Upon the end of treatment periods, expression of tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), NADPH oxidase (NOX2), SERCA2a were measured from the heart. A computational approach including network pharmacology, protein-protein interaction (PPI) network, molecular docking, and dynamic was performed to understand the molecular mechanism of ECGTT against cardiac damage in MetS.

Results: Chlorogenic acid (CGA), epigallocatechin gallate (EGCG), and curcumin were identified as the main metabolites in ECGTT. The ECGTT administration decreased the TNFα, IL-6, NF-κB, and NOX2 and increased SERCA2a expression(p<0.05). Moreover, the PPI result suggested that angiotensin II receptor type 1 (AGTR1) was the key regulator of cardiac injury-MetS induced. CGA, EGCG, and curcumin bind to AGTR1 with smaller binding energy than metformin and showed stability of structure and interaction among those metabolites into AGTR1.

Conclusions: Coffee, green tea, and turmeric might prevent heart dysfunction in MetS through modulation of oxidative stress and inflammation.

Keywords: calcium handling; coffee; green tea; inflammation; oxidative stress; turmeric.

jppres_pdf_free

Resumen

Contexto: Se requiere el desarrollo de bebidas funcionales para inhibir el estrés oxidativo y la inflamación como proceso crítico en la inducción del daño cardiaco en el síndrome metabólico. Se ha demostrado que el café, el té y la cúrcuma ofrecen ventajas para la salud.

Objetivos: Investigar el efecto del extracto de café, té verde y cúrcuma (ECGTT) contra el síndrome cardiometabólico (MetS).

Métodos: Se identificaron los metabolitos secundarios del café, el té verde y la cúrcuma mediante LC-HRMS. Las ratas macho Sprague-Dawley se dividieron en cuatro grupos (n = 4) que representaban los grupos normal, MetS, MetS con dosis de tratamiento ECGTT: 300/100/150 mg de peso corporal y 300/100/250 mg de peso corporal. Al final de los periodos de tratamiento, se midió en el corazón la expresión del factor de necrosis tumoral alfa (TNFα), la interleucina-6 (IL-6), el factor nuclear kappa B (NF-κB), la NADPH oxidasa (NOX2) y la SERCA2a. Se realizó un enfoque computacional que incluía farmacología de red, red de interacción proteína-proteína (PPI), acoplamiento molecular y dinámica para comprender el mecanismo molecular de ECGTT contra el daño cardíaco en MetS.

Resultados: El ácido clorogénico (CGA), el galato de epigalocatequina (EGCG) y la curcumina se identificaron como los principales metabolitos en ECGTT. La administración de ECGTT redujo el TNFα, IL-6, NF-κB y NOX2 y aumentó la expresión de SERCA2a (p<0,05). Además, el resultado de la IPP sugirió que el receptor de angiotensina II tipo 1 (AGTR1) era el regulador clave de la lesión cardiaca inducida por MetS. CGA, EGCG y la curcumina se unen a AGTR1 con menor energía de unión que la metformina y mostró la estabilidad de la estructura y la interacción entre los metabolitos en AGTR1.

Conclusiones: El café, el té verde y la cúrcuma podrían prevenir la disfunción cardiaca en MetS a través de la modulación del estrés oxidativo y la inflamación.

Palabras Clave: café; cúrcuma; estrés oxidativo; inflamación; manejo del calcio; té verde.

jppres_pdf_free
Citation Format: Rachmawati E, Rohman MS, Widodo N, Lukitasari M, Nugroho DA, Hermanto FE, Kholis MN (2023) The analysis of coffee-green tea-turmeric combination against cardiac-metabolic syndrome using metabolite profiling, gene expression, and in silico approach. J Pharm Pharmacogn Res 11(6): 961–974. https://doi.org/10.56499/jppres23.1702_11.6.961
References

Akasaka H, Katsuya T, Saitoh S, Sugimoto K, Fu Y, Takagi S, Ohnishi H, Rakugi H, Ura N, Shimamoto K, Ogihara T (2006) Effects of angiotensin II type 1 receptor gene polymorphisms on insulin resistance in a Japanese general population: the Tanno-Sobetsu study. Hypertens Res 29(12): 961–967. https://doi.org/10.1291/hypres.29.961

Alshehri AM (2010) Metabolic syndrome and cardiovascular risk. J Community Med 17(2): 73–78. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045098/

Balderas-Villalobos J, Molina-Muñoz T, Mailloux-Salinas P, Bravo G, Carvajal K, Gómez-Viquez NL (2013) Oxidative stress in cardiomyocytes contributes to decreased SERCA2a activity in rats with metabolic syndrome. Am J Physiol Heart Circ Physiol 305(9): H1344–H1353. https://doi.org/10.1152/ajpheart.00211.2013

Battault S, Renguet E, van Steenbergen A, Horman S, Beauloye C, Bertrand L (2020) Myocardial glucotoxicity: Mechanisms and potential therapeutic targets. Arch Cardiovasc Dis 113(11): 736–748. https://doi.org/10.1016/j.acvd.2020.06.006

Bhatti SN, Li JM (2020) Nox2 dependent redox-regulation of Akt and ERK1/2 to promote left ventricular hypertrophy in dietary obesity of mice. Biochem Biophys Res Comm 528(3): 506–513. https://doi.org/10.1016/j.bbrc.2020.05.162

Burnier M, Egan BM (2019) Adherence in hypertension: A review of prevalence, risk factors, impact, and management. Circ Res 124(7): 1124–1140. https://doi.org/10.1161/CIRCRESAHA.118.313220

Calvert JW (2014) Nox2 targets SERCA in response to a high fat high sugar diet. J Mol Cell Cardiol 72: 228–230. https://doi.org/10.1016/j.yjmcc.2014.03.018

de Geest B, Mishra M (2022) Role of oxidative stress in diabetic cardiomyopathy. Antioxidants (Basel) 11(4): 784. https://doi.org/10.3390/antiox11040784

D’Oria R, Schipani R, Leonardini A, Natalicchio A, Perrini S, Cignarelli A, Laviola L, Giorgino F (2020) The role of oxidative stress in cardiac disease: From physiological response to injury factor. Oxid Med Cell Longev 2020: 5732956. https://doi.org/10.1155/2020/5732956

Esmaeelpanah E, Razavi BM, Hosseinzadeh H (2021) Green tea and metabolic syndrome: A 10-year research update review. Iran J Basic Med Sci 24(9): 1159–1172. https://doi.org/10.22038/ijbms.2021.52980.11943

Ferreira LG, Dos Santos RN, Oliva G, Andricopulo AD (2015) Molecular docking and structure-based drug design strategies. Molecules 20(7): 13384–13421. https://doi.org/10.3390/molecules200713384

Firzan N, Andri F, Sukamto SM, Andi DP, Mirnawati S, Deepak C, Talha BE, Jesus S (2023) Natural products targeting inflammation-related metabolic disorders: A comprehensive review. Heliyon 9: 6. https://doi.org/10.1016/j.heliyon.2023.e16919

Fung MM, Rao F, Poddar S, Mahata M, Khandrika S, Mahata SK, O’Connor DT (2011) Early inflammatory and metabolic changes in association with AGTR1 polymorphisms in prehypertensive subjects. Am J Hypertens 24(2): 225–233, https://doi.org/10.1038/ajh.2010.210

Gogoi B, Chowdhury P, Goswami N, Gogoi N, Naiya T, Chetia P (2021) Identification of potential plant based inhibitor against viral proteases of SARS CoV 2 through molecular docking, MM PBSA binding energy calculations and molecular dynamics simulation. Mol Divers 25(3): 1963–1977. https://doi.org/10.1007/s11030-021-10211-9

Khan H, Ullah H, Nabavi SM (2019) Mechanistic insights of hepatoprotective effects of curcumin: Therapeutic updates and future prospects. Food Chem Toxicol 124: 182–191. https://doi.org/10.1016/j.fct.2018.12.002

Khan I, Rahman H, Abd El-Salam NM, Tawab A, Hussain A, Khan TA, Khan UA, Qasim M, Adnan M, Azizullah A, Murad W, Jalal A, Muhammad N, Ullah R (2017) Punica granatum peel extracts: HPLC fractionation and LC MS analysis to quest compounds having activity against multidrug resistant bacteria. BMC Complement Alternat Med 17(1): 247. https://doi.org/10.1186/s12906-017-1766-4

Kucera O, Mezera V, Moravcova A, Endlicher R, Lotkova H, Drahota Z, Cervinkova Z (2015) In vitro toxicity of epigallocatechin gallate in rat liver mitochondria and hepatocytes. Oxid Med Cell Longev 2015: 476180. https://doi.org/10.1155/2015/476180

Lau SO, Georgousopoulou EN, Kellett J, Thomas J, McKune A, Mellor D, Roach PD, Naumovski N (2016) The effect of dietary supplementation of green tea catechins on cardiovascular disease risk markers in humans: A systematic review of clinical trials. Beverages 2(2): 16. https://doi.org/10.3390/beverages2020016

Lukitasari M, Nugroho D, Rohman M, Widodo N, Farmawati A, Hastuti P (2020) Beneficial effects of green coffee and green tea extract combination on metabolic syndrome improvement by affecting AMPK and PPAR-α gene expression. J Adv Pharm Technol Res 11(2): 81–85. https://doi.org/10.4103/japtr.JAPTR_116_19

Ly LD, Xu S, Choi SK, Ha CM, Thoudam T, Cha SK, Wiederkehr A, Wollheim CB, Lee IK, Park KS (2017) Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes. Exp Mol Med 49: e291. https://doi.org/10.1038/emm.2016.157

Pan Y, Wang Y, Zhao Y, Peng K., Li W, Wang Y, Zhang J, Zhou S, Liu Q, Li X, Cai L, Liang G (2014) Inhibition of JNK phosphorylation by a novel curcumin analog prevents high glucose-induced inflammation and apoptosis in cardiomyocytes and the development of diabetic cardiomyopathy. Diabetes 63(10): 3497–3511. https://doi.org/10.2337/db13-1577

Patti AM, Al-Rasadi K, Giglio RV, Nikolic D, Mannina C, Castellino G, Chianetta R, Banach M, Cicero AFG, Lippi G, Montalto G, Rizzo M, Toth PP (2018) Natural approaches in metabolic syndrome management. Arch Med Scie 14(2): 422–441. https://doi.org/10.5114/aoms.2017.68717

Qin F, Siwik DA, Luptak I, Hou X, Wang L, Higuchi A, Weisbrod RM, Ouchi N, Tu VH, Calamaras TD, Miller EJ, Verbeuren TJ, Walsh K, Cohen RA, Colucci WS (2012) The polyphenols resveratrol and S17834 prevent the structural and functional sequelae of diet-induced metabolic heart disease in mice. Circulation 125: 1757–1764. https://doi.org/10.1161/CIRCULATIONAHA.111.067801

Qin Z, Hou X, Weisbrod RM, Seta F, Cohen RA, Tong X (2014) Nox2 mediates high fat high sucrose diet-induced nitric oxide dysfunction and inflammation in aortic smooth muscle cells. J Mol Cell Cardiol 72: 56-63. http://doi.org/10.1016/j.yjmcc.2014.02.019

Rachmawati E, Rohman MS, Sargowo D, Kalsum U, Lyrawati D, Lukitasari M (2021) Decaffeinated coffee and green tea extract inhibit foam cell atherosclerosis by lowering inflammation and improving cholesterol influx/efflux balance through upregulation of PPARγ and miR-155. F1000Research 10: 1175. https://doi.org/10.12688/f1000research.74198.1

Rachmawati E, Rohman MS, Sishartami LW, Sargowo D, Kalsum U (2022) In silico modelling, regulation of cell viability and anti atherosclerotic effect in macrophage by decaffeinated coffee and green tea extract. Pharmacogn J 14(1): 46–55. https://doi.org/10.5530/pj.2022.14.7

Rohman MS, Lukitasari M, Nugroho AD, Nashi W, Nugraheini NIP, Sardjono WT (2017) Development of an experimental model of metabolic syndrome in Sprague Dawley rat. Res Jf Life Sci 4(1): 76–86. https://doi.org/10.21776/ub.rjls.2017.004.01.10

Saleh HA, Ramdan E, Elmazar MM, Azzazy HME, Abdelnaser A (2021) Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS/IFN-γ-mediated inflammation in doxorubicin-treated macrophages. Sci Rep 11(1): 545. https://doi.org/10.1038/S41598-020-80804-1

Shi Z, Zhu J X, Guo Y M, Niu M, Zhang L, Tu C, Huang Y, Li PY, Zhao X, Zhang ZT, Bai ZF, Zhang GQ, Lu Y, Xiao XH, Wang JB (2021) Epigallocatechin gallate during dietary restriction — potential mechanisms of enhanced liver injury. Front Pharmacol 11: 609378. https://doi.org/10.3389/fphar.2020.609378

Su G, Morris JH, Demchak B, Bader GD (2015) Biological network exploration with cytoscape 3. Curr Protoc Bioinformatics 47: 8.13.1-24. https://doi.org/10.1002/0471250953.bi0813s47

Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou K P, Kuhn M, Bork P, Jensen LJ, von Mering C (2015) STRING v10: Protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43(D1): D447–D452. https://doi.org/10.1093/nar/gku1003

Tabatabaei-Malazy O, Larijani B, Abdollahi M (2015) Targeting metabolic disorders by natural products. J Diabetes Metab Disord 14: 57. https://doi.10.1186/s40200-015-0184-8

Tang WH, Cheng WT, Kravtsov GM, Tong XY, Hou XY, Chung SK, Sum S, Chung M, Chung SSM (2010) Cardiac contractile dysfunction during acute hyperglycemia due to impairment of SERCA by polyol pathway-mediated oxidative stress. Am J Physiol Cell Physiol 299: 643–653. https://doi.org/10.1152/ajpcell.00137.2010

Valdés Á, Treuer AV, Barrios G, Ponce N, Fuentealba R, Dulce RA, González DR (2018) NOX inhibition improves β-adrenergic stimulated contractility and intracellular calcium handling in the aged rat heart. Int J Mol Sci 19(8): 2404. https://doi.org/10.3390/ijms19082404

Villarroel-Vicente C, Gutiérrez-Palomo S, Ferri J, Cortes D, Cabedo N (2021) Natural products and analogs as preventive agents for metabolic syndrome via peroxisome proliferator-activated receptors: An overview. Eur J Med Chem 221: 113535. https://doi.org/10.1016/j.ejmech.2021.113535

Villegas S, Villarreal FJ, Dillmann WH (2000) Leukemia inhibitory factor and interleukin-6 downregulate sarcoplasmic reticulum Ca2+ ATPase (SERCA2) in cardiac myocytes. Basic Res Cardiol 95(1): 47–54. https://doi.org/10.1007/s003950050007

Wang M, Liu Y, Liang Y, Naruse K, Takahashi K (2021) Systematic understanding of pathophysiological mechanisms of oxidative stress-related conditions—diabetes mellitus, cardiovascular diseases, and ischemia– reperfusion injury. Front Cardiovasc Med 8: 649785. https://doi.org/10.3389/fcvm.2021.649785

Yu Z, Samavat H, Dostal AM, Wang R, Torkelson CJ, Yang CS, Butler LM, Kensler TW, Wu AH, Kurzer MS, Yuan JM (2017) Effect of green tea supplements on liver enzyme elevation: Results from a randomized intervention study in the United States. Cancer Prev Res (Phila) 10(10): 571–579. https://doi.org/10.1158/1940-6207.CAPR-17-0160

© 2023 Journal of Pharmacy & Pharmacognosy Research

Molybdenum blue assay for estimating antioxidant activity

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 953-960, Nov-Dec 2023.

DOI: https://doi.org/10.56499/jppres23.1646_11.6.953

Original Article

Optimization of the molybdenum blue method for estimating the antioxidant activity of natural products

[Optimización del método del azul de molibdeno para estimar la actividad antioxidante de productos naturales]

Enoel Hernández-Barreto1, Vivian Ruz-Sanjuan1*, Venancio Ribalta-Ribalta1, Luis A. Torres-Gómez2

1Department of Pharmacy, Central University “Marta Abreu” of Las Villas (UCLV), Santa Clara, PC 54830, Cuba.

2Institute of Pharmacy and Food (IFAL), University of Havana, Havana, PC 13600, Cuba.

*E-mail: vivianr@uclv.edu.cu

Abstract

Context: The present experimental conditions of the molybdenum blue spectrophotometric method, used for antioxidant activity estimation, promote the degradation of flavonoids with potential interferences in the above determination.

Aims: To evaluate the effects of physicochemical factors on the formation of the complex for optimizing the total antioxidant activity method to better estimate the antioxidant activity of natural products.

Methods: A 34-1 fractional experimental design was applied. Independent variables were temperature, color development time, type of acid and acidity, and the dependent variable was the absorbance of the complex. The concentration of ammonium molybdate tetrahydrate and sodium hydrogen phosphate remained constant throughout the study. The effects of the reducing agent and its concentration were studied independently. The effect of acidity in a wide range of values, the color development time considering temperature, the influence of co-solvents, and the antioxidant activity of various natural metabolites were also evaluated.

Results: Acid concentration and temperature greatly influenced the complex formation, making the type of acid and incubation time less significant. Ascorbic acid showed a shorter color development time than reference metabolites. Ethanol negatively influenced the amount of complex formed. The proposed conditions for developing this method were: type of acid, HCl or H2SO4; acid concentration 0.01 N; incubation temperature 65°C; and incubation time 40 min. Under these experimental conditions, the ranking order of antioxidant activity was pyrogallol>quercetin>ascorbic acid>gallic acid>rutin.

Conclusions: The new experimental conditions for the molybdenum complex assay give a more reliable determination of the antioxidant activity of natural products.

Keywords: antioxidants; flavonoids; molybdenum blue; research design.

jppres_pdf_free

Resumen

Contexto: Las condiciones experimentales actuales del método espectrofotométrico del azul de molibdeno, utilizado para la estimación de la actividad antioxidante, favorecen la degradación de los flavonoides con potenciales interferencias en la determinación anterior.

Objetivos: Evaluar los efectos de los factores fisicoquímicos en la formación del complejo para optimizar el método de actividad antioxidante total para una mejor estimación de la actividad antioxidante de los productos naturales.

Métodos: Se aplicó un diseño experimental fraccionado 34-1. Las variables independientes fueron la temperatura, el tiempo de desarrollo del color, el tipo de ácido y la acidez, y la variable dependiente fue la absorbancia del complejo. La concentración de molibdato amónico tetrahidratado y de hidrogenofosfato sódico se mantuvo constante durante todo el estudio. Los efectos del agente reductor y su concentración se estudiaron de forma independiente. También se evaluó el efecto de la acidez en un amplio rango de valores, el tiempo de desarrollo del color considerando la temperatura, la influencia de los co-solventes y la actividad antioxidante de varios metabolitos naturales.

Resultados: La concentración de ácido y la temperatura influyeron en gran medida en la formación de complejos, siendo menos significativos el tipo de ácido y el tiempo de incubación. El ácido ascórbico mostró un tiempo de desarrollo del color más corto que los metabolitos de referencia. El etanol influyó negativamente en la cantidad de complejo formado. Las condiciones propuestas para desarrollar este método fueron: tipo de ácido, HCl o H2SO4; concentración de ácido 0,01 N; temperatura de incubación 65°C; y tiempo de incubación 40 min. En estas condiciones experimentales, el orden de clasificación de la actividad antioxidante fue pirogalol>quercetina>ácido ascórbico>ácido gálico>rutina.

Conclusiones: Las nuevas condiciones experimentales para el ensayo del complejo de molibdeno proporcionan una determinación más fiable de la actividad antioxidante de los productos naturales.

Palabras Clave: antioxidantes; azul de molibdeno; diseño experimental; flavonoides.

jppres_pdf_free
Citation Format: Hernández-Barreto E, Ruz-Sanjuan V, Ribalta-Ribalta V, Torres-Gómez LA (2023) Optimization of the molybdenum blue method for estimating the antioxidant activity of natural products. J Pharm Pharmacogn Res 11(6): 953–960. https://doi.org/10.56499/jppres23.1646_11.6.953
References

Ali HM, Abo-Shady A, Sharaf Eldeen HA, Soror HA, Shousha WG (2013) Structural features, kinetics and SAR study of radical scavenging and antioxidant activities of phenolic and anilinic compounds. Chem Cent J 7: 3–7. https://doi.org/10.1186/1752-153X-7-53

Ami D, Davidovic D, Beslo D, Rastija V, Trinajstic N (2007) SAR and QSAR of the antioxidant activity of flavonoids. Curr Med Chem 14: 829. https://doi.org/10.2174/092986707780090954

Anokwah D, Kwatia EA, Amponsah IK, Jibira Y, Harley BK, Ameyaw EO, Obese E, Biney RP, Mensah AY (2022) Evaluation of the anti-inflammatory and antioxidant potential of the stem bark extract and some constituents of Aidia genipiflora (DC.) Dandy (Rubiaceae). Heliyon 8: e10082. https://doi.org/1016/j.heliyon.2022.e10082

Asghar M, Sajjad A, Hanif S, Ali JS, Ali Z, Zia M (2022) Comparative analysis of synthesis, characterization, antimicrobial, antioxidant, and enzyme inhibition potential of roses petal based synthesized copper oxide nanoparticles. Mat Chem Phys 278: 125724. https://doi.org/10.1016/j.matchemphys.2022.125724

Banjarnahor SDS, Artanti N (2014) Antioxidant properties of flavonoids. Med J Indones 23: 240–243. https://doi.org/10.13181/mji.v23i4.1015

Bijelic A, Aureliano M, Rompel A (2019) Polyoxometalates as potential next-generation metallodrugs in the combat against cancer. Angew Chem 58: 2980–2999. https://doi.org/10.1002/anie.201803868

Chaaban H, Ioannou I, Chebil L, Slimane M, Ghoul M (2017) Effect of heat processing on thermal stability and antioxidant activity of six flavonoids. J Food Process Preserv 41: e13203.https://doi.org/10.1111/jfpp.13203

Cherevan AS, Nandan SP, Roger I, Liu R, Streb C, Eder D (2020) Polyoxometalates on functional substrates: Concepts, synergies, and future perspectives. Adv Scie 7: 1903511. https://doi.org/10.1002/advs.201903511

Echeverry SM, Medina HI, Costa GM, Aragón DM (2018) Optimization of flavonoid extraction from Passiflora quadrangularis leaves with sedative activity and evaluation of its stability under stress conditions. Rev Bras Farmacogn 28: 610–617. https://doi.org/10.1016/j.bjp.2018.06.005

Gavrilova N, Myachina M, Harlamova D, Nazarov V (2020) Synthesis of molybdenum blue dispersions using ascorbic acid as reducing agent. Colloid Interface 4: 24. https://doi.org/10.3390/colloids4020024

Iorio A, Rendina A, Porcelli C, Bargiela M, Gorgoschidse L (1991) Estabilidad del complejo azul de fosfomolibdeno influencia de la acidez del medio y tiempo de desarrollo del color. Rev Fac Agron [Buenos Aires] 12: 249–252.

Liu Q, Wang X (2020) Polyoxometalate clusters: Sub-nanometer building blocks for construction of advanced materials. Matter 2: 816–841. https://doi.org/10.1016/j.matt.2020.01.020

Long D-L, Burkholder E, Cronin L (2007) Polyoxometalate clusters, nanostructures and materials: From self-assembly to designer materials and devices. Chem Soc Rev 36: 105–121. https://doi.org/10.1039/B502666K

Myachina M, Gavrilova N, Nazarov V (2021) Formation of molybdenum blue nanoparticles in the organic reducing area. Molecules 26: 4438. https://doi.org/10.3390/molecules26154438

Nazarudin MF, Yasin ISM, Mazli NAIN, Saadi AR, Azizee MHS, Nooraini MA, Saad N, Ferdous UT, Fakhrulddin IM (2022) Preliminary screening of antioxidant and cytotoxic potential of green seaweed, Halimeda opuntia (L.) Lamouroux. Saudi J Biol Sci 29: 2698–2705. https://doi.org/10.1016/j.sjbs.2021.12.066

Patel SB, Ghane SG (2021) Phyto-constituents profiling of Luffa echinata and in vitro assessment of antioxidant, anti-diabetic, anticancer and anti-acetylcholine esterase activities. Saudi J Biol Sci 28: 3835–3846. https://doi.org/10.1016/j.sjbs.2021.03.050

Popoola OO (2022) Phenolic compounds composition and in vitro antioxidant activity of Nigerian Amaranthus viridis seed as affected by autoclaving and germination. Measurement Food 6: 100028. https://doi.org/10.1016/j.meafoo.2022.100028

Prieto P, Pineda M, Aguilar M (1999) Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E. Anal Biochem 269: 337–341. https://doi.org/10.1006/abio.1999.4019

Purewal SS, Kaur P, Sandhu KS (2022) Bioactive profile and antioxidant properties of Kinnow seeds: A report broadening its potential. Appl Food Res 2: 100135. https://doi.org/10.1016/j.afres.2022.100135

Qiao L, Sun Y, Chen R, Fu Y, Zhang W, Li X, Chen J, Shen Y, Ye X (2014) Sonochemical effects on 14 flavonoids common in citrus: relation to stability. PloS One 9: e87766. https://doi.org/10.1371/journal.pone.0105647

Ramešová Š, Sokolová R, Degano I, Bulíčková J, Žabka J, Gál M (2011) On the stability of the bioactive flavonoids quercetin and luteolin under oxygen-free conditions. Anal Bioanal Chem 402: 976–981. https://doi.org/10.1007/s00216-011-5504-3

Wang J, Zhao X-H (2016) Degradation kinetics of fisetin and quercetin in solutions affected by medium pH, temperature and co-existing proteins J Serb Chem Soc 81: 243–253. https://doi.org/10.2298/JSC150706092W

© 2023 Journal of Pharmacy & Pharmacognosy Research

SLCO1B1/ CYP3A4 associated with adverse reactions to statins

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 934-952, Nov-Dec 2023.

DOI: https://doi.org/10.56499/jppres23.1686_11.6.934

Review

SLCO1B1 and CYP3A4 allelic variants associated with pharmacokinetic interactions and adverse reactions induced by simvastatin and atorvastatin used in Peru: Clinical implications

[Variantes alélicas de SLCO1B1 y CYP3A4 asociadas a interacciones farmacocinéticas y reacciones adversas inducidas por simvastatina y atorvastatina usadas en el Perú: Implicaciones clínicas]

Angel T. Alvarado1*, Ana María Muñoz2, Roberto O. Ybañez-Julca3, Mario Pineda-Pérez4, Nesquen Tasayco-Yataco5, María R. Bendezú6, Jorge A. García6, Felipe Surco-Laos6, Haydee Chávez6, Doris Laos-Anchante6, Aura Molina-Cabrera6, Carmela Ferreyra-Paredes6, Nelly Vega-Ramos6, Patricia Castillo-Romero6, Javier Chávez-Espinoza6, Juan Panay-Centeno6, Eliades Yarasca-Carlos7

1International Research Unit in Molecular Pharmacology and Genomic Medicine (UNIPHARMAGEM), VRI San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

2Institute of Food Science and Nutrition, ICAN, San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

3Faculty of Pharmacy and Biochemistry, National University of Trujillo, 13006, Trujillo, Peru.

4Pharmacy and Biochemistry, Faculty of Health Sciences, Scientific University of the South, UCSUR, 15067, Lima, Peru.

5Human Medicine, Norbert Wiener University, 15046, Lima, Peru.

6Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University of Ica, 11004, Ica, Peru.

7Biological Sciences Faculty, San Luis Gonzaga National University of Ica, 11001, Ica, Peru.

*E-mail: angel.alvaradoy@usil.pe

Abstract

Context: Statins reduce the risk of stroke and prevent cardiac events in people with atherosclerosis and diabetes mellitus; and could affect the proliferation, migration, and survival of cancer cells.

Aims: To review the most up-to-date and available scientific evidence on the allelic variants of SLCO1B1 and CYP3A4 associated with pharmacokinetic interactions and adverse reactions induced by simvastatin and atorvastatin used in Peru, and their clinical implications.

Methods: The bibliographic search was carried out in the PubMed/Medline, Google Scholar and Science Direct databases. The keywords were: “statin”, “atorvastatin”, “simvastatin” in combination with “pharmacokinetics”, “pharmacogenetics”, “CYP3A4”, “SLCO1B1” or “drug interactions” considering the eligibility criteria defined by the PRISMA-2020 international statement.

Results: Scientific evidence indicates a significant association between SLCO1B1 rs4149056 c.521T>C (521CC and 521TC) and increased plasma levels, area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax) of simvastatin, compared to wild-type SLCO1B1*1/*1 521TT (p<0.05). SLCO1B1 521C is not associated with atorvastatin (p>0.05). Patients with SLCO1B1 521CC had a significantly higher risk of myopathy and rhabdomyolysis induced by simvastatin compared to TT (p<0.05). An association was also found between CYP3A4*1/*22/CYP3A4*3/*22 and increased pharmacokinetic parameters of simvastatin compared to CYP3A4*1/*1 (p< 0.05).

Conclusions: Based on the review of the published scientific evidence, it is concluded that individuals carrying the allelic variants SLCO1B1 (c.521T>C), CYP3A4*1/*22 and CYP3A4*3/*22 could be associated with an increase in the pharmacokinetic parameters and with an increased risk of myopathy and rhabdomyolysis induced by simvastatin, and not by atorvastatin.

Keywords: adverse reactions; atorvastatin; CYP3A4; pharmacokinetic interactions; SLCO1B1; simvastatin.

jppres_pdf_free

Resumen

Contexto: Las estatinas reducen el riesgo accidente cerebrovascular y previene los eventos cardíacos en personas con aterosclerosis y diabetes mellitus; y podría afectar la proliferación, migración y supervivencia de las células cancerosas.

Objetivos: Revisar la evidencia científica más actualizada y disponible sobre las variantes alélicas de SLCO1B1 y CYP3A4 asociadas a interacciones farmacocinéticas y reacciones adversas inducidas por la simvastatina y atorvastatina usadas en el Perú, y sus implicaciones clínicas.

Métodos: Se realizó la búsqueda bibliográfica en bases de datos PubMed/Medline, Google Scholar and Science Direct databases. Las palabras clave fueron: “estatina”, “atorvastatina”, “simvastatina” en combinación con “farmacocinética”, “farmacogenética”, “CYP3A4”, “SLCO1B1” o “interacciones con fármacos” teniendo en cuenta los criterios de elegibilidad definidos por la declaración internacional PRISMA-2020.

Resultados: La evidencia científica indica asociación significativa entre SLCO1B1 rs4149056 c.521T>C (521CC y 521TC) y el aumento de los niveles plasmáticos, del área bajo la curva de concentraciones plasmáticas (AUC) y concentración plasmática máxima (Cmax) de simvastatina, respecto al wild-type SLCO1B1*1/*1 521TT (p<0.05). SLCO1B1 521C no está asociado con atorvastatina (p>0.05). Los pacientes con SLCO1B1 521CC presentaron mayor riesgo significativo de miopatía y rabdomiólisis inducida por simvastatina frente a TT (p< 0.05). También se encontró asociación entre CYP3A4*1/*22/CYP3A4*3/*22 y aumento de los parámetros farmacocinéticos de simvastatina en comparación con CYP3A4*1/*1 (p < 0.05).

Conclusiones: Basado en la revisión de la evidencia científica publicada se concluye que los individuos portadores de las variantes alélicas SLCO1B1 (c.521T>C), CYP3A4*1/*22 y CYP3A4*3/*22 podrían estar asociados a un incremento de los parámetros farmacocinéticos y con un mayor riesgo de miopatía y rabdomiólisis inducida por simvastatina, y no por atorvastatina.

Palabras Clave: atorvastatina; CYP3A4; interacciones farmacocinéticas; reacción adversa; SLCO1B1; simvastatina.

jppres_pdf_free
Citation Format: Alvarado AT, Muñoz AM, Ybañez RO, Pineda M, Tasayco N, Bendezú G, García JA, Surco F, Chávez H, Laos D, Molina A, Ferreyra C, Vega N, Castillo P, Chávez J, Panay J, Yarasca E (2023) SLCO1B1 and CYP3A4 allelic variants associated with pharmacokinetic interactions and adverse reactions induced by simvastatin and atorvastatin used in Peru: Clinical implications. J Pharm Pharmacogn Res 11(6): 934–952. https://doi.org/10.56499/jppres23.1686_11.6.934
References

Ahangari N, Doosti M, Ghayour Mobarhan M, Sahebkar A, Ferns GA, Pasdar A (2020) Personalised medicine in hypercholesterolaemia: the role of pharmacogenetics in statin therapy. Ann Med 52(8): 462–470. https://doi.org/10.1080/07853890.2020.1800074

Alvarado A, García G, Morales A, Paredes G, Mora M, Muñoz AM, Pariona R, Bendezú MR, Chávez H, García JÁ, Laos-Anchante D, Loja-Herrera B, Bolarte-Arteaga M, Pineda M (2022b) Phenytoin concentration in people with epilepsy: A comparative study in serum and saliva. Pharmacia 69(3): 809–814. https://doi.org/10.3897/pharmacia.69.e87168

Alvarado AT, Cotuá J, Delgado M, Morales A, Muñoz AM, Li C, Bendezú MR, García JÁ, Laos-Anchante D, Surco-Laos F, Loja B, Bolarte-Arteaga M, Pineda-Pérez M (2022a) Serum concentrations of valproic acid in people with epilepsy: Clinical implication. J Pharm Pharmacogn Res 10(6): 1117–1125. https://doi.org/10.56499/jppres22.1500_10.6.1117

Alvarado AT, Muñoz AM, Bendezú M, García JA, Palomino-Jhong JJ, Ochoa-Pachas G, Chonn-Chang A, Sullon-Dextre L, Loja-Herrera B, Pineda-Perez M (2021a) In vitro biopharmaceutical equivalence of 5-mg glibenclamide tablets in simulated intestinal fluid without enzymes. Dissolution Technol 28(1): 1–12. https://doi.org/10.14227/DT280121PGC2

Alvarado AT, Muñoz AM, Bendezú MR, Palomino-Jhong JJ, García JA, Alvarado CA, Alvarado EA, Ochoa-Pachas G, Pineda-Pérez M, Bolarte M (2021b) In vitro biopharmaceutical equivalence of carbamazepine sodium tablets available in Lima, Peru. Dissolution Technol 28(2): 1–10. https://dx.doi.org/10.14227/DT280221PGC2

Alvarado AT, Muñoz AM, Loja B, Miyasato JM, García JÁ, Cerro RA, Quiñones LA, Varela NM (2019) Study of the allelic variants CYP2C9*2 and CYP2C9*3 in samples of the Peruvian mestizo population. Biomédica 39(3): 601–610. http://dx.doi.org/10.7705/biomedica.4636

Alvarado AT, Paredes G, García G, Morales A, Muñoz AM, Saravia M, Losno R, Bendezú MR, Chávez H, García JÁ, Pineda M, Sullón-Dextre L (2022c) Serum monitoring of carbamazepine in patients with epilepsy and clinical implications. Pharmacia 69(2): 401–406. http://dx.doi.org/10.3897/pharmacia.69.e82425

Alvarado AT, Saravia M, Losno R, Pariona R, Muñoz AM, Ybañez-Julca R, Loja B, Bendezú MR, García JÁ, Laos-Anchante D, Chávez H, Aguilar P, Pineda M (2023) CYP2D6 and CYP2C19 genes associated with tricontinental and Latin American ancestry of Peruvians. Drug Metab Bioanal Lett 16(1): 14–26. https://doi.org/10.2174/1872312815666221213151140

Alvarado AT, Ybañez-Julca R, Muñoz AM, Tejada-Bechi C, Cerro R, Quiñones LA, Varela N, Alvarado CA, Alvarado E, Bendezú MR, García JÁ (2021c) Frequency of CYP2D6*3 and *4 and metabolizer phenotypes in three mestizo Peruvian populations. Pharmacia 68(4): 891–898. http://dx.doi.org/10.3897/pharmacia.68.e75165

Apellániz-Ruiz M, Inglada-Pérez L, Naranjo MEG, Sánchez L, Mancikova V, Currás-Freixes M, de Cubas AA, Comino-Méndez I, Triki S, Rebai A, Rasool M, Moya G, Grazina M, Opocher G, Cascón A, Taboada-Echalar P, Ingelman-Sundberg M, Carracedo A, Robledo M, Llerena A, Rodríguez-Antona C (2015b) High frequency and founder effect of the CYP3A4*20 loss-of-function allele in the Spanish population classifies CYP3A4 as a polymorphic enzyme. Pharmacogenomics J 15: 288–292. https://doi.org/10.1038/tpj.2014.67

Apellániz-Ruiz M, Lee MY, Sanchez L, Gutierrez-Gutierrez G, Calvo I, Garcia-Estevez L, Sereno M, García-Donás J, Castelo B, Guerra E, Leandro-García LJ, Cascón A, Johansson I, Robledo M, Ingelman-Sundberg M, Rodríguez-Antona C (2015a) Whole-exome sequencing reveals defective CYP3A4 variants predictive of paclitaxel dose-limiting neuropathy. Clin Cancer Res 21(2): 322–328. https://doi.org/10.1158/1078-0432.CCR-14-1758

Arguedas JA (2002) Actualización en farmacoterapia: La Farmacología de las estatinas: Primera Parte. Rev Costarric Cardiol 4(1): 13–21.

Bartra M, Losno García R, Valderrama-Wong M, Muñoz Jáuregui AM, Bendezú Acevedo M, García Ceccarelli J, Surco Laos F, Basurto Ayala P, Pineda-Pérez M, Alvarado AT (2021) Interacciones farmacocinéticas de la azitromicina e implicación clínica. Rev Cub Med Mil 50(3): e02101284.

Cai T, Abel L, Langford O, Monaghan G, Aronson JK, Stevens RJ, Lay-Flurrie S, Koshiaris C, McManus RJ, Hobbs FDR, Sheppard JP (2021) Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses. BMJ 374: n1537. https://doi.org/10.1136/bmj.n1537

Catalán J, Garay J, Romero F, Miranda C, Roco A, Quiñones L, Saavedra I (2011) Metabolismo de los antipsicóticos: enzimas y genes relacionados.  Rev Farmacol Chile 4(1): 15–20.

Choi HY, Bae KS, Cho SH, Ghim JL, Choe S, Jung JA, Jin SJ, Kim HS, Lim HS (2015) Impact of CYP2D6, CYP3A5, CYP2C19, CYP2A6, SLCO1B1, ABCB1, and ABCG2 gene polymorphisms on the pharmacokinetics of simvastatin and simvastatin acid. Pharmacogenet Genomics 25(12): 595–608. https://doi.org/10.1097/FPC.0000000000000176

Choi MK, Shin HJ, Choi YL, Deng JW, Shin JG, Song IS (2011) Differential effect of genetic variants of Na(+)-taurocholate co-transporting polypeptide (NTCP) and organic anion-transporting polypeptide 1B1 (OATP1B1) on the uptake of HMG-CoA reductase inhibitors. Xenobiotica 41(1): 24–34. https://doi.org/10.3109/00498254.2010.523736

Cooper-DeHoff RM, Niemi M, Ramsey LB, Luzum JA, Tarkiainen EK, Straka RJ, Gong L, Tuteja S, Wilke RA, Wadelius M, Larson EA, Roden DM, Klein TE, Yee SW, Krauss RM, Turner RM, Palaniappan L, Gaedigk A, Giacomini KM, Caudle KE, Voora D (2022) The clinical pharmacogenetics implementation consortium guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clin Pharmacol Ther 111(5): 1007–1021. https://doi.org/10.1002/cpt.2557

Courlet P, Decosterd LA, Alves Saldanha S, Cavassini M, Stader F, Stoeckle M, Buclin T, Marzolini C, Csajka C, Guidi M, Swiss HIV Cohort Study (2020) Influence of drug-drug interactions on the pharmacokinetics of atorvastatin and its major active metabolite ortho-OH-atorvastatin in aging people living with HIV. Clin Pharmacokinet 59: 1037–1048. https://doi.org/10.1007/s40262-020-00876-0

Dagli-Hernandez C, Zhou Y, Lauschke VM, Genvigir FDV, Hirata TDC, Hirata MH, Hirata RDC (2022) Pharmacogenomics of statins: Lipid response and other outcomes in Brazilian cohorts. Pharmacol Rep 74: 47–66. https://doi.org/10.1007/s43440-021-00319-y

Díaz Rodríguez N, Serrano Cumplido A, Fierro González D, Rodríguez Arroyo LA, García-Norro FJ, de Abajo Olea S, López Rodríguez I, Panisello Royo JM, Minguez Villar JC, Palomo del Arco J, Chacartegui RC, Fuster VP, Verdes-Montenegro JC (2012) Pitavastatin: A new alternative in the treatment of dyslipidemia. [Spanish]. Clin Invest Arterioscl 24(1): 30–39. https://doi.org/10.1016/j.arteri.2011.10.005

Du Y, Wang S, Chen Z, Sun S, Zhao Z, Li X (2018) Association of SLCO1B1 polymorphisms and atorvastatin safety and efficacy: A meta-analysis. Curr Pharm Des 24(34): 4044–4050. https://doi.org/10.2174/1381612825666181219163534

Echaniz-Laguna A, Mohr M, Tranchant C (2010) Neuromuscular symptoms and elevated creatine kinase after statin withdrawal. N Engl J Med 362: 564–565. https://doi.org/10.1056/NEJMc0908215

Elalem EG, Jelani M, Khedr A, Ahmad A, Alaama TY, Alaama MN, Al-Kreathy HM, Damanhouri ZA (2022) Association of cytochromes P450 3A4*22 and 3A5*3 genotypes and polymorphism with response to simvastatin in hypercholesterolemia patients. PLoS One 17(7): e0260824. https://doi.org/10.1371/journal.pone.0260824

Elens L, van Gelder T, Hesselink DA, Haufroid V, van Schaik RH (2013) CYP3A4*22: Promising newly identified CYP3A4 variant allele for personalizing pharmacotherapy. Pharmacogenomics 14(1): 47–62. https://doi.org/10.2217/pgs.12.187

Fernandes Silva L, Ravi R, Vangipurapu J, Oravilahti A, Laakso M (2022) Effects of SLCO1B1 Genetic variant on metabolite profile in participants on simvastatin treatment. Metabolites 12(12): 1159. https://doi.org/10.3390/metabo12121159

Ghim JL, Phuong N, Kim MJ, Kim EJ, Song GS, Ahn S, Shin JG, Kim EY (2019) Pharmacokinetics of fixed-dose combination of atorvastatin and metformin compared with individual tablets. Drug Des Devel Ther 13: 1623–1632. https://doi.org/10.2147/DDDT.S193254

Guan ZW, Wu KR, Li R, Yin Y, Li XL, Zhang SF, Li Y (2019) Pharmacogenetics of statins treatment: Efficacy and safety. J Clin Pharm Ther 44(6): 858–867. https://doi.org/10.1111/jcpt.13025

Hirota T, Fujita Y, Ieiri I (2020) An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins. Expert Opin Drug Metab Toxicol 16(9): 809–822. https://doi.org/10.1080/17425255.2020.1801634

Hirota T, Ieiri I (2015) Drug-drug interactions that interfere with statin metabolism. Expert Opin Drug Metab Toxicol 11(9): 1435-1447. https://doi.org/10.1517/17425255.2015.1056149

Holbrook A, Wright M, Sung M, Ribic C, Baker S (2011) Statin-associated rhabdomyolysis: is there a dose-response relationship? Can J Cardiol 27(2): 146–151. https://doi.org/10.1016/j.cjca.2010.12.024

Hou Q, Li S, Li L, Li Y, Sun X, Tian H (2015) Association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk: A meta-analysis of case-control studies. Medicine 94(37): e1268. https://doi.org/10.1097/MD.0000000000001268

Hronová K, Šíma M, Světlík S, Matoušková O, Slanař O (2014) Pharmacogenetics and immunosuppressive drugs. Expert Rev Clin Pharmacol 7(6): 821–835. https://doi.org/10.1586/17512433.2014.966811

Huang WC, Lin TW, Chiou KR, Cheng CC, Kuo FY, Chiang CH, Yang JS, Lin KL, Hsiao SH, Yeh TC, Mar GY, Hsiao HC, Lin SL, Chiou CW, Liu CP (2013) The effect of intensified low density lipoprotein cholesterol reduction on recurrent myocardial infarction and cardiovascular mortality. Acta Cardiol Sin 29(5): 404–412. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804789/

Inoue K, Inazawa J, Nakagawa H, Shimada T, Yamazaki H, Guengerich FP, Abe T (1992) Assignment of the human cytochrome P-450 nifedipine oxidase gene (CYP3A4) to chromosome 7 at band q22.1 by fluorescence in situ hybridization. Jpn J Hum Genet 37: 133–138. https://doi.org/10.1007/BF01899734

Jacobsen W, Kuhn B, Soldner A, Kirchner G, Sewing KF, Kollman PA, Benet LZ, Christians U (2000) Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos 28(11): 1369–1378. https://pubmed.ncbi.nlm.nih.gov/11038166/

Jessurun NT, Drent M, Wijnen PA, Harmsze AM, van Puijenbroek EP, Bekers O, Bast A (2021) Role of drug–gene interactions and pharmacogenetics in simvastatin‑associated pulmonary toxicity. Drug Saf 44: 1179–1191. https://doi.org/10.1007/s40264-021-01105-8

Jiang F, Choi JY, Lee JH, Ryu S, Park ZW, Lee JG, Na HS, Lee SY, Oh WY, Chung MW, Choi SE (2017) The influences of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin, in relation to CYP3A4 inhibition. Pharmacogenomics 18(5): 459–469. https://doi.org/10.2217/pgs-2016-0199

Joy TR, Hegele RA (2009) Narrative review: Statin-related myopathy. Ann Intern Med 150: 858–868. https://doi.org/10.7326/0003-4819-150-12-200906160-00009

Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P (2012) Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): Influence of protein expression on drug-drug interactions. J Med Chem 55(10): 4740–4763. https://doi.org/10.1021/jm300212s

Kearney AS, Crawford LF, Mehta SC, Radebaugh GW (1993) The interconversion kinetics, equilibrium, and solubilities of the lactone and hydroxyacid forms of the HMG-CoA reductase inhibitor, CI-981. Pharm Res 10: 1461–1465. https://doi.org/10.1023/a:1018923325359

Kim JR, Jung JA, Kim S, Huh W, Ghim JL, Shin JG, Ko JW (2019) Effect of cilostazol on the pharmacokinetics of simvastatin in healthy subjects. Biomed Res Int 2019: 1365180. https://doi.org/10.1155/2019/1365180

Kim KA, Park PW, Lee OJ, Kang DK, Park JY (2007) Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects. J Clin Pharmacol 47(1): 87–93. https://doi.org/10.1177/0091270006295063

Kitzmiller JP, Luzum JA, Baldassarre D, Krauss RM, Medina MW (2014) CYP3A4*22 and CYP3A5*3 are associated with increased levels of plasma simvastatin concentrations in the cholesterol and pharmacogenetics study cohort. Pharmacogenet Genomics 24(10): 486–491. https://doi.org/10.1097/FPC.0000000000000079

Kuypers DR (2018) What do we know about tacrolimus pharmacogenetics in transplant recipients? Pharmacogenomics 19(7): 593–597. https://doi.org/10.2217/pgs-2018-0035

Linskey DW, English JD, Perry DA, Ochs-Balcom HM, Ma C, Isackson PJ, Vladutiu GD, Luzum JA (2020) Association of SLCO1B1 c.521T>C (rs4149056) with discontinuation of atorvastatin due to statin-associated muscle symptoms. Pharmacogenet Genomics 30(9): 208–211. https://doi.org/10.1097/FPC.0000000000000412

Lu B, Sun L, Seraydarian M, Hoffmann TJ, Medina MW, Risch N, Iribarren C, Krauss RM, Oni-Orisan A (2021) Effect of SLCO1B1 T521C on statin-related myotoxicity with use of lovastatin and atorvastatin. Clin Pharmacol Ther 110(3): 733–740. https://doi.org/10.1002/cpt.2337

Luzum JA, Theusch E, Taylor KD, Wang A, Sadee W, Binkley PF, Krauss RM, Medina MW, Kitzmiller JP (2015) Individual and combined associations of genetic variants in CYP3A4, CYP3A5, and SLCO1B1 with simvastatin and simvastatin acid plasma concentrations. J Cardiovasc Pharmacol 66(1): 80–85. https://doi.org/10.1097/FJC.0000000000000246

Maekawa K, Harakawa N, Yoshimura T, Kim SR, Fujimura Y, Aohara F, Sai K, Katori N, Tohkin M, Naito M, Hasegawa R, Okuda H, Sawada JI, Niwa T, Saito Y (2010) CYP3A4*16 and CYP3A4*18 alleles found in East Asians exhibit differential catalytic activities for seven CYP3A4 substrate drugs. Drug Metab Dispos 38(12): 2100–2104. https://doi.org/10.1124/dmd.110.034140

Masson W (2019) Uso adecuado de las estatinas de alta intensidad. Rev Urug Cardiol 34: 349–359. https://doi.org/10.29277/cardio.34.3.24

Mykkänen AJH, Taskinen S, Neuvonen M, Paile-Hyvärinen M, Tarkiainen EK, Lilius T, Tapaninen T, Backman JT, Tornio A, Niemi M (2022) Genomewide association study of simvastatin pharmacokinetics. Clin Pharmacol Ther 112(3): 676–686. https://doi.org/10.1002/cpt.2674

Nieto I, Chengwin C, Atehortúa L, Sepúlveda L (2013) Las estatinas: Química, técnicas analíticas, biosíntesis y farmacocinética. Vitae 20(1): 49–63.

Olaya Ramírez F, Medina Arango A, Navas Lenis M, Tilano Acevedo A, Monsalve I, González Bustamente A, Rincón P (2011) Estudio farmacocinético de la asociación atorvastatina 40 mg + ezetimibe 10 mg tabletas. Arch Venez Farmacol Ter 30(1): 15–22.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D (2021) The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 372: n71. https://doi.org/10.1136/bmj.n71

Pedersen TR, Tobert JA (2004) Simvastatin: a review. Expert Opin Pharmacother 5(12): 2583–2596. https://doi.org/10.1517/14656566.5.12.2583

Peng C, Ding Y, Yi X, Shen Y, Dong Z, Cao L, Li Q, Ren H, He L, Zhou D, Chen X (2018) Polymorphisms in CYP450 genes and the therapeutic effect of atorvastatin on ischemic stroke: A retrospective cohort study in Chinese population. Clin Ther 40(3): 469–77.e2. https://doi.org/10.1016/j.clinthera.2018.02.002

Plant N (2007) The human cytochrome P450 sub-family: transcriptional regulation, inter-individual variation and interaction networks. Biochim Biophys Acta 1770(3): 478–488. https://doi.org/10.1016/j.bbagen.2006.09.024

Prueksaritanont T, Gorham LM, Ma B, Liu L, Yu X, Zhao JJ, Slaughter DE, Arison BH, Vyas KP (1997) In vitro metabolism of simvastatin in humans [SBT]identification of metabolizing enzymes and effect of the drug on hepatic P450s. Drug Metab Dispos 25(10): 1191–1199. https://pubmed.ncbi.nlm.nih.gov/9321523/

Prueksaritanont T, Subramanian R, Fang X, Ma B, Qiu Y, Lin JH, Pearson PG, Baillie TA (2002) Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab Dispos 30(5): 505–512. https://doi.org/10.1124/dmd.30.5.505

Ramsey LB, Johnson SG, Caudle KE, Haidar CE, Voora D, Wilke RA, Maxwell WD, McLeod HL, Krauss RM, Roden DM, Feng Q, Cooper-DeHoff RM, Gong L, Klein TE, Wadelius M, Niemi M (2014) The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther 96(4): 423–428. https://doi.org/10.1038/clpt.2014.125

Robledo M, Torres I, Manrique RD, Duque M, Gallo JE (2019) Utilidad del gen SLCO1B1como marcador de interés en la farmacogenómica de las estatinas. Rev Colomb Cardiol 26(1): 24–30. https://doi.org/10.1016/j.rccar.2018.05.006

Rojas-Macetas A, Medalla-Garro G, Saravia M, Losno R, Valderrama-Wong M, Pariona R, Alvarado AT (2023) Potential polymorphic CYP1A2 and CYP2D6-mediated pharmacokinetic interactions between risperidone or olanzapine and selected drugs intended to treat COVID-19. Drug Metab Bioanal Lett 16(1): 6–13. https://doi.org/10.2174/1872312815666221125112724

Saiz-Rodríguez M, Almenara S, Navares-Gómez M, Ochoa D, Román M, Zubiaur P, Koller D, Santos M, Mejía G, Borobia AM, Rodríguez-Antona C, Abad-Santos F (2020) Effect of the most relevant CYP3A4 and CYP3A5 polymorphisms on the pharmacokinetic parameters of 10 CYP3A substrates. Biomedicines 8(4): 94. https://doi.org/10.3390/biomedicines8040094

Shaghaghi Z, Alvandi M, Farzipour S, Dehbanpour MR, Nosrati S (2023) A review of effects of atorvastatin in cancer therapy. Med Oncol 40: 27. https://doi.org/10.1007/s12032-022-01892-9

Sirtori CR (2014) The pharmacology of statins. Pharmacol Res 88: 3–11. https://doi.org/10.1016/j.phrs.2014.03.002

Soria-Chacartegui P, Villapalos-García G, Zubiaur P, Abad-Santos F, Koller D (2021) Genetic polymorphisms associated with the pharmacokinetics, pharmacodynamics and adverse effects of olanzapine, aripiprazole and risperidone. Front Pharmacol 12: 711940. https://doi.org/10.3389/fphar.2021.711940

Stillemans G, Paquot A, Muccioli GG, Hoste E, Panin N, Åsberg A, Balligand JL, Haufroid V, Elens L (2022) Atorvastatin population pharmacokinetics in a real-life setting: Influence of genetic polymorphisms and association with clinical response. Clin Transl Sci 15(3): 667–679. https://doi.org/10.1111/cts.13185

Tanaka E (1998) Clinically important pharmacokinetic drug-drug interactions: role of cytochrome P450 enzymes. J Clin Pharm Ther 23(6): 403–416. https://doi.org/10.1046/j.1365-2710.1998.00086.x

Taylor F, Huffman MD, Macedo AF, Moore THM, Burke M, Smith GD, Ward K, Ebrahim S, Gay HC (2013) Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013: CD004816. https://doi.org/10.1002/14651858.CD004816.pub5

Uçkun Z, Baskak B, Özdemir H, Özel-Kizil ET, Devrimci-Özgüven H, Süzen HS (2018) Genotype and allele frequency of CYP3A4 -392A>G in Turkish patients with major depressive disorder. Turk J Pharm Sci 15(2): 200–206. https://doi.org/10.4274/tjps.46320

Vanwong N, Tipnoppanon S, Na Nakorn C, Srisawasdi P, Rodcharoen P, Medhasi S, Chariyavilaskul P, Siwamogsatham S, Vorasettakarnkij Y, Sukasem C (2022) Association of drug-metabolizing enzyme and transporter gene polymorphisms and lipid-lowering response to statins in thai patients with dyslipidemia. Pharmacogenomics Pers Med 2022(15): 119–130. https://doi.org/10.2147/PGPM.S346093

Vickers S, Duncan CA, Vyas KP, Kari PH, Arison B, Prakash SR, Ramjit HG, Pitzenberger SM, Stokker G, Duggan DE (1990) In vitro and in vivo biotransformation of simvastatin, an inhibitor of HMG CoA reductase. Drug Metab Dispos 18(4): 476–483. https://pubmed.ncbi.nlm.nih.gov/1976071/

Vildhede A, Karlgren M, Svedberg EK, Wisniewski JR, Lai Y, Norén A, Artursson P (2014) Hepatic uptake of atorvastatin: influence of variability in transporter expression on uptake clearance and drug-drug interactions. Drug Metab Dispos 42(7): 1210–1218. https://doi.org/10.1124/dmd.113.056309

Wagner JB, Abdel-Rahman S, Van Haandel L, Gaedigk A, Gaedigk R, Raghuveer G, Kauffman R, Leeder JS (2018) Impact of SLCO1B1 genotype on pediatric simvastatin acid pharmacokinetics. J Clin Pharmacol 58(6): 823–833. https://doi.org/10.1002/jcph.1080

Wang CW, Preclaro IAC, Lin WH, Chung WH (2022) An updated review of genetic associations with severe adverse drug reactions: translation and implementation of pharmacogenomic testing in clinical practice. Front Pharmacol 13: 886377. https://doi.org/10.3389/fphar.2022.886377

Westlind-Johnsson A, Hermann R, Huennemeyer A, Hauns B, Lahu G, Nassr N, Zech K, Ingelman-Sundberg M, von Richter O (2006) Identification and characterization of CYP3A4*20, a novel rare CYP3A4 allele without functional activity. Clin Pharmacol Ther 79(4): 339–349. https://doi.org/10.1016/j.clpt.2005.11.015

Wilke RA, Ramsey LB, Johnson SG, Maxwell WD, McLeod HL, Voora D, Krauss RM, Roden DM, Feng Q, Cooper-Dehoff RM, Gong L, Klein TE, Wadelius M, Niemi M (2012) The Clinical Pharmacogenomics Implementation Consortium: CPIC Guideline for SLCO1B1 and simvastatin-induced myopathy. Clin Pharmacol Ther 92(1): 112–117. https://doi.org/10.1038/clpt.2012.57

Xiang Q, Chen SQ, Ma LY, Hu K, Zhang Z, Mu GY, Xie QF, Zhang XD, Cui YM (2018) Association between SLCO1B1 T521C polymorphism and risk of statin-induced myopathy: a meta-analysis. Pharmacogenomics J 18: 721–729. https://doi.org/10.1038/s41397-018-0054-0

Zhang Q, Qu H, Chen Y, Luo X, Chen C, Xiao B, Ding X, Zhao P, Lu Y, Chen AF, Yu Y (2022) Atorvastatin induces mitochondria-dependent ferroptosis via the modulation of Nrf2-xCT/GPx4 Axis. Front Cell Dev Biol 10: 806081. https://doi.org/10.3389/fcell.2022.806081

Zhou Q, Ruan ZR, Jiang B, Yuan H, Zeng S (2013) Simvastatin pharmacokinetics in healthy Chinese subjects and its relations with CYP2C9, CYP3A5, ABCB1, ABCG2 and SLCO1B1 polymorphisms. Pharmazie 68(2): 124–128. https://pubmed.ncbi.nlm.nih.gov/23469684/

Zhou Q, Yu X, Shu C, Cai Y, Gong W, Wang X, Wang DM, Hu S (2011) Analysis of CYP3A4 genetic polymorphisms in Han Chinese. J Hum Genet 56: 415–422. https://doi.org/10.1038/jhg.2011.30

Zhou XY, Hu XX, Wang CC, Lu XR, Chen Z, Liu Q, Hu GX, Cai JP (2019) Enzymatic activities of CYP3A4 allelic variants on quinine 3-hydroxylation in vitro. Front Pharmacol 10: 591. https://doi.org/10.3389/fphar.2019.00591

© 2023 Journal of Pharmacy & Pharmacognosy Research

Anti-angiogenic effect of neoadjuvant chemotherapy

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 926-933, Nov-Dec 2023.

DOI: https://doi.org/10.56499/jppres23.1695_11.6.926

Original Article

Check update pattern of tumorigenic vasculature signature based on MMP9 and CXCR4 expression in locally advanced breast cancer

[Comprobación del patrón de actualización de la señal de vasculatura tumorigénica basada en la expresión de MMP9 y CXCR4 en el cáncer de mama localmente avanzado]

Mochamad Bachtiar Budianto1, Hamzah Sulaiman Lubis2, Muhammad Luqman Fadli3, Wiwit Nurwidyaningtyas4,5*

1Department Oncology of Saiful Anwar General Hospital, Malang 65112, Indonesia.

2Department Oncology of Medan Hajj General Hospital, Sumatera Utara 20371,Indonesia.

3Department Anatomy Pathology of Saiful Anwar General Hospital, Malang 65112, Indonesia.

4Department Molecular and Cellular Biology, Sekolah Tinggi Ilmu Kesehatan Kendedes, Malang, 65126, Indonesia.

5Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency (BRIN), Genomic Building, Cibinong Science Center, Jl. Raya Bogor No. 490, Cibinong – Bogor Km. 46, Bogor, West Java, Indonesia.

*E-mail: wiwi026@brin.go.id

Abstract

Context: Locally advanced breast cancers (LABC) are the most common women malignant tumors. Appropriate vasculature is required for tumor growth support, formed by involving protein signaling, including matrix metalloprotein 9 (MMP9) and C-X-C chemokine receptor type 4 (CXCR4). Neoadjuvant chemotherapy (NAC) administration to inoperable LABC commonly exhibits a positive response, although recurrences may be encountered in a few cases.

Aims: To evaluate the MMP9 and CXCR4 expression shifting after the NAC procedure to establish evidence of the anti-angiogenic effect of NAC, which encourages knowledge of tumor size reduction pathways in LABC.

Methods: Observational designs were conducted in this study. Tissue specimens before and after NAC were collected from 45 LABC-enrolled subjects. The targeted protein expression was analyzed by immunohistochemistry, and stained sections were classified according to the percentage of nuclear-stained tumor cells. Clinicopathological features of LABC were recorded. Tumor size was measured by Vernier caliper before and after NAC.

Results: The results showed the nuclear expression of MMP9 and CXCR4 protein were observed in all tissue specimens. The expression of MMP9 and CXCR4 tended to decrease after the NAC but was not statistically significant for MMP9. There was a significant correlation between expression levels of CXCR4 and tumor size reduction (p<0.001) but not for MMP9.

Conclusions: The results of this study demonstrate the anti-angiogenic effect of NAC by inhibiting MMP9 and CXCR4, which may be integrated with tumor size reduction in LABC. Further studies are required to highlight the possibility of recurrence following inhibition of MMP9 and CXCR4 by NAC.

Keywords: breast cancers; CXCR4; MMP9; neoadjuvant chemotherapy; positive response.

jppres_pdf_free

Resumen

Contexto: Los cánceres de mama localmente avanzados (LABC) son los tumores malignos femeninos más frecuentes. Se requiere una vasculatura adecuada para el soporte del crecimiento tumoral, formada por la implicación de la señalización de proteínas, incluyendo la metaloproteína de matriz 9 (MMP9) y el receptor de quimioquinas C-X-C tipo 4 (CXCR4). La administración de quimioterapia neoadyuvante (NAC) al LABC inoperable suele mostrar una respuesta positiva, aunque en algunos casos pueden producirse recidivas.

Objetivos: Evaluar el cambio de expresión de MMP9 y CXCR4 tras el procedimiento NAC para establecer evidencias del efecto antiangiogénico de la NAC, lo que favorece el conocimiento de las vías de reducción del tamaño tumoral en el LABC.

Métodos: En este estudio se realizaron diseños observacionales. Se recogieron muestras de tejido antes y después de la NAC de 45 sujetos inscritos en el LABC. La expresión de la proteína diana se analizó mediante inmunohistoquímica, y las secciones teñidas se clasificaron según el porcentaje de células tumorales teñidas nuclearmente. Se registraron las características clinicopatológicas del LABC. El tamaño del tumor se midió con un calibre Vernier antes y después de la NAC.

Resultados: Los resultados mostraron la expresión nuclear de las proteínas MMP9 y CXCR4 en todas las muestras de tejido. La expresión de MMP9 y CXCR4 tendió a disminuir tras la NAC, pero no fue estadísticamente significativa para MMP-9. Se observó una correlación significativa entre los niveles de expresión de CXCR4 y la reducción del tamaño del tumor (p<0,001). Hubo una correlación significativa entre los niveles de expresión de CXCR4 y la reducción del tamaño del tumor (p<0,001), pero no para MMP9.

Conclusiones: os resultados de este estudio demuestran el efecto antiangiogénico de la NAC mediante la inhibición de MMP9 y CXCR4, que puede integrarse con la reducción del tamaño tumoral en el LABC. Se requieren más estudios para poner de relieve la posibilidad de recurrencia tras la inhibición de MMP9 y CXCR4 por NAC.

Palabras Clave: cánceres de mama; CXCR4; MMP9; quimioterapia neoadyuvante; respuesta positiva.

jppres_pdf_free
Citation Format: Budianto M, Lubis H, Fadli M, Nurwidyaningtyas W (2023) Check update pattern of tumorigenic vasculature signature based on MMP9 and CXCR4 expression in locally advanced breast cancer. J Pharm Pharmacogn Res 11(6): 926–933. https://doi.org/10.56499/jppres23.1695_11.6.926
References

ACS – The American Cancer Society Medical and Editorial Content Team (2021) Understanding a Breast Cancer Diagnosis. cancer.org. https://www.cancer.org/content/dam/CRC/PDF/Public/8580.00.pdf. [Accessed 12 June 2023].

Aebi S, Karlsson P, Wapnir IL (2022). Locally advanced breast cancer. Breast (Edinburgh, Scotland) 62: 58–62. https://doi.org/10.1016/j.breast.2021.12.011

Al-Saleh K, Salah T, Arafah M, Husain S, Al-Rikabi A, Abd El-Aziz N (2021) Prognostic significance of estrogen, progesterone, and HER2 receptors’ status conversion following neoadjuvant chemotherapy in patients with locally advanced breast cancer: Results from a tertiary Cancer Center in Saudi Arabia. PLoS One 16: e0247802. https://doi.org/10.1371/journal. pone.0247802

Angeles MA, Baissas P, Leblanc E, Lusque A, Ferron G, Ducassou A (2019) Magnetic resonance imaging after external beam radiotherapy and concurrent chemotherapy for locally advanced cervical cancer helps to identify patients at risk of recurrence. Int J Gynecol Cancer 29: 480−486. https://doi.org/10.1136/ijgc-2018-000168

An J, Peng C, Tang H, Liu X, Peng F (2021) New advances in the research of resistance to neoadjuvant chemotherapy in breast cancer. Int J Mol Sci 22: 9644. https://doi.org/10.3390/ijms22179644

Augoff K, Hryniewicz-Jankowska A, Tabola R, Stach K (2022) MMP9: A tough target for targeted therapy for cancer. Cancers 14: 1847. https://doi.org/10.3390/cancers14071847

Ayoub NM, Jaradat SK, Al-Shami KM, Alkhalifa AE (2022) Targeting angiogenesis in breast cancer: Current evidence and future perspectives of novel anti-angiogenic approaches. Front Pharmacol 13: 838133. https://doi.org/10.3389/fphar.2022.838133

Balogun OD, Formenti SC (2015) Locally advanced breast cancer – strategies for developing nations. Front Oncol 5: 89. https://doi.org/10.3389/fonc.2015.00089

Barillari G (2020) The impact of matrix metalloproteinase-9 on the sequential steps of the metastatic process. Int J Mol Sci 21: 4526. https://doi.org/10.3390/ijms21124526

Bianchi ME, Mezzapelle R (2020) The chemokine receptor CXCR4 in cell proliferation and tissue regeneration. Front Immunol 11: 2109. https://doi.org/10.3389/fimmu.2020.02109

Cadona FC, Machado AK, Montano MAE, Assmann CE, da Cruz IBM (2017) Overview of locally advanced breast cancer: A huge challenge to science. Int J Womens Health Wellness 3: 044. http://doi.org/10.23937/2474-1353/1510044

Chang A, Sloan EK, Antoni MH, Knight JM, Telles R, Lutgendorf SK (2022) Biobehavioral pathways and cancer progression: Insights for improving well-being and cancer outcomes. Integr Cancer Ther 21: 15347354221096081. https://doi.org/10.1177/15347354221096081

Cordoba A, Durand B, Escande A, Taieb S, Amor MBH, Le Deley MC, Michel A, Le Tinier F, Hudry D, Martinez C, Leblanc E, Becourt S, Abdedaim C, Bresson L, Lartigau E, Mirabel X and Narducci F (2022) Prognostic impact of tumor size reduction assessed by magnetic resonance imaging after radiochemotherapy in patients with locally advanced cervical cancer. Front Oncol 12: 1046087. https://doi.org/10.3389/fonc.2022.1046087

Dhanushkodi M, Sridevi V, Shanta V, Rama R, Swaminathan R, Selvaluxmy G, Ganesan TS (2021) Locally Advanced Breast Cancer (LABC): Real-world outcome of patients from Cancer Institute, Chennai. JCO Glob Oncol 7: 767–781. https://doi.org/10.1200/GO.21.00001

Faustino-Rocha A, Oliveira PA, Pinho-Oliveira J, Teixeira-Guedes C, Soares-Maia R, da Costa RG, Colaço B, Pires MJ, Colaço J, Ferreira R, Ginja M (2013) Estimation of rat mammary tumor volume using caliper and ultrasonography measurements. Lab Animal 42: 217–224. https://doi.org/10.1038/laban.254

Gogia A, Deo SV, Shukla NK, Mathur S, Sharma DN, Tiwari A (2018) Clinicopathological profile of breast cancer: An institutional experience. Indian J Cancer 55: 210–213. https://doi.org/10.4103/ijc.IJC_73_18

Guo F, Wang Y, Liu J, Mok SC, Xue F, Zhang W (2016) CXCL12/CXCR4: A symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks. Oncogene 35: 816–826. https://doi.org/10.1038/onc.2015.139

He W, Yang T, Gong XH, Qin RZ, Zhang XD, Liu, WD (2018) Targeting CXC motif chemokine receptor 4 inhibits the proliferation, migration, and angiogenesis of lung cancer cells. Oncology Lett 16: 3976–3982. https://doi.org/10.3892/ol.2018.9076

Jiang H, Li H (2021) Prognostic values of tumoral MMP2 and MMP9 overexpression in breast cancer: A systematic review and meta-analysis. BMC Cancer 21: 149. https://doi.org/10.1186/s12885-021-07860-2

Joseph C, Alsaleem M, Orah N, Narasimha PL, Miligy IM, Kurozumi S, Ellis IO, Mongan NP, Green AR, Rakha EA (2020) Elevated MMP9 expression in breast cancer is a predictor of shorter patient survival. Breast Cancer Res Treat 182: 267–282. https://doi.org/10.1007/s10549-020-05670-x

Korde LA, Somerfield MR, Carey LA, Crews JR, Denduluri N, Hwang ES, Khan SA, Loibl S, Morris EA, Perez A, Regan MM, Spears PA, Sudheendra PK, Symmans WF, Yung RL, Harvey BE, Hershman DL (2021) Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO Guideline. J Clin Oncol 39: 1485–1505. https://doi.org/10.1200/JCO.20.03399

Larionova I, Kazakova E, Gerashchenko T, Kzhyshkowska J (2021) New angiogenic regulators produced by TAMs: Perspective for targeting tumor angiogenesis. Cancers 13: 3253. https://doi.org/10.3390/cancers13133253

Lefort S, Thuleau A, Kieffer Y, Sirven P, Bieche I, Marangoni E, Vincent-Salomon A, Mechta-Grigoriou F (2017) CXCR4 inhibitors could benefit to HER2 but not to triple-negative breast cancer patients. Oncogene 36: 1211–1222. https://doi.org/10.1038/onc.2016.284

Li H, Qiu Z, Li F, Wang C (2017) The relationship between MMP-2 and MMP-9 expression levels with breast cancer incidence and prognosis. Oncology Lett 14: 5865–5870. https://doi.org/10.3892/ol.2017.6924

Luker KE, Lewin SA, Mihalko LA, Schmidt BT, Winkler JS, Coggins NL, Thomas DG, Luker GD (2012) Scavenging of CXCL12 by CXCR7 promotes tumor growth and metastasis of CXCR4-positive breast cancer cells. Oncogene 31: 4750–4758. https://doi.org/10.1038/onc.2011.633

Ma J, Su H, Yu B, Guo T, Gong Z, Qi J, Zhao X, Du J (2018) CXCL12 gene silencing down-regulates metastatic potential via blockage of MAPK/PI3K/AP-1 signaling pathway in colon cancer. Clin Transl Oncol 20: 1035–1045. https://doi.org/10.1007/s12094-017-1821-0

Masood S (2016) Neoadjuvant chemotherapy in breast cancers. Womens Health 12: 480–491. https://doi.org/10.1177/1745505716677139

Oshi M, Takahashi H, Tokumaru Y, Yan L, Rashid OM, Nagahashi M, Matsuyama R, Endo I, Takabe K (2020) The E2F pathway score as a predictive biomarker of response to neoadjuvant therapy in ER+/HER2- breast cancer. Cells 9: 1643. https://doi.org/10.3390/cells9071643

Poltavets V, Faulkner JW, Dhatrak D, Whitfield RJ, McColl SR, Kochetkova M (2021) CXCR4-CCR7 heterodimerization is a driver of breast cancer progression. Life 11: 1049. https://doi.org/10.3390/life11101049

Shi Y, Riese DJ, Shen J (2020) The role of the CXCL12/CXCR4/CXCR7 chemokine axis in cancer. Front Pharmacol 11: 574667. https://doi.org/10.3389/fphar.2020.574667

Soliman NA, Yussif SM (2016) Ki-67 as a prognostic marker according to breast cancer molecular subtype. Cancer Biol Med 13: 496–504. https://doi.org/10.20892/j.issn.2095-3941.2016.0066

Wei DM, Chen WJ, Meng RM (2018) Augmented expression of Ki-67 is correlated with clinicopathological characteristics and prognosis for lung cancer patients: an up-dated systematic review and meta-analysis with 108 studies and 14,732 patients. Respir Res 19: 150. https://doi.org/10.1186/s12931-018-0843-7

Winkler J, Abisoye-Ogunniyan A, Metcalf KJ, Werb Z (2020). Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat Comm 11: 5120. https://doi.org/10.1038/s41467-020-18794-x

Wu HT, Lin J, Liu YE, Chen HF, Hsu KW, Lin SH, Peng KY, Lin KJ, Hsieh CC, & Chen DR (2021) Luteolin suppresses androgen receptor-positive triple-negative breast cancer cell proliferation and metastasis by epigenetic regulation of MMP9 expression via the AKT/mTOR signaling pathway. Phytomedicine 81: 153437. https://doi.org/10.1016/j.phymed.2020.153437

Xu C, Zhao H, Chen H, Yao Q (2015) CXCR4 in breast cancer: oncogenic role and therapeutic targeting. Drug Des Devel Ther 9: 4953–4964. https://doi.org/10.2147/DDDT.S84932

Zielińska KA, Katanaev VL (2020) The signaling duo CXCL12 and CXCR4: Chemokine fuel for breast cancer tumorigenesis. Cancers 12: 3071. https://doi.org/10.3390/cancers12103071

Zhang Z, Ni C, Chen W, Wu P, Wang Z, Yin J, Huang J, Qu F (2014) Expression of CXCR4 and breast cancer prognosis: a systematic review and meta-analysis. BMC Cancer 14: 49. https://doi.org/10.1186/1471-2407-14-49

© 2023 Journal of Pharmacy & Pharmacognosy Research

N-Benzoyl-N’-phenylthiourea derivatives and macrophage migration inhibitory factor

J. Pharm. Pharmacogn. Res., vol. 11, no. 5, pp. 902-925, Sep-Oct 2023.

DOI: https://doi.org/10.56499/jppres23.1657_11.5.902

Original Article

Synthesis and in vitro activity tests of N-benzoyl-N’-phenylthiourea derivatives as macrophage migration inhibitory factor

[Síntesis y pruebas de actividad in vitro de derivados de N-benzoil-N’-feniltiourea como factor inhibidor de la migración de macrófagos]

Dini Kesuma1, Galih S. Putra2*, Tegar A. Yuniarta1,Farida Suhud1, I G.A. Sumartha1, Sawitri Boengas3, Melanny I. Sulistyowaty4, Tjie Kok5

1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Surabaya, Surabaya, Indonesia.

2Department of Chemistry, Faculty of Mathematics and Natural Sciences, State University of Malang, Malang Indonesia.

3Faculty of Medicine, University of Surabaya, Surabaya, Indonesia.

4Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia.

5 Faculty of Biotechnology, University of Surabaya, Surabaya, Indonesia.

*E-mail: galih.satrio.fmipa@um.ac.id

Abstract

Context: The COVID-19 pandemic in 2020 resulted in widespread mortalities due to cytokine storms in the affected patients. Macrophage migration inhibitory factor (MIF) is one of the most interesting targets in developing anti-COVID-19 drugs. Some thiourea compounds have been identified as having potential as MIF inhibitors.

Aims: To investigate MIF inhibitory activity of N-benzoyl-N’-phenylthiourea derivatives.

Methods: The study consists of in-silico activity prediction of designed compounds using a molecular docking approach against MIF protein (PDB ID: 1LJT). Afterwards, the designed compounds were synthesized and tested in vitro using the tautomerase activity approach.

Results: The molecular docking study showed that all designed compounds possess comparable docking scores to the native ligand of the protein. MIF Assay performed on compounds (1) and (2) indicated a decrease in tautomerase activity of the MIF target protein of only 10.1 and 6.2%, respectively, compared to the positive control.

Conclusions: In silico results predicted better bioactivity against MIF protein, but the result does not translate to the in vitro assay, where two of the designed compounds possess only low inhibitory activity.

Keywords: 1LJT; MIF assay; tautomerase activity; thiourea derivatives.

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Resumen

Contexto: La pandemia de COVID-19 en 2020 provocó mortalidades generalizadas debido a las tormentas de citocinas en los pacientes afectados. El factor inhibidor de la migración de macrófagos (MIF) es una de las dianas más interesantes en el desarrollo de fármacos anti-COVID-19. Se han identificado algunos compuestos de tiourea con potencial como inhibidores de MIF.

Objetivos: Investigar la actividad inhibidora de MIF de derivados de N-benzoil-N’-feniltiourea.

Métodos: El estudio consiste en la predicción in silico de la actividad de los compuestos diseñados utilizando un enfoque de acoplamiento molecular frente a la proteína MIF (PDB ID: 1LJT). Posteriormente, los compuestos diseñados se sintetizaron y probaron in vitro mediante el método de actividad tautomerasa.

Resultados: El estudio de acoplamiento molecular mostró que todos los compuestos diseñados poseen puntuaciones de acoplamiento comparables al ligando nativo de la proteína. El ensayo MIF realizado con los compuestos (1) y (2) indicó una disminución de la actividad tautomerasa de la proteína diana MIF de sólo el 10,1 y el 6,2%, respectivamente, en comparación con el control positivo.

Conclusiones: Los resultados in silico predijeron una mejor bioactividad frente a la proteína MIF, pero el resultado no se traslada al ensayo in vitro, donde dos de los compuestos diseñados sólo poseen una baja actividad inhibitoria.

Palabras Clave: actividad tautomerasa; derivados tiourea; ensayo MIF; 1LJT.

jppres_pdf_free
Citation Format: Kesuma D, Putra GS, Yuniarta TA, Suhud F, Sumartha IGA, Boengas S, Sulistyowati MI, Kok T (2023) Synthesis and in vitro activity tests of N-benzoyl-N'-phenylthiourea derivatives as macrophage migration inhibitory factor. J Pharm Pharmacogn Res 11(5): 902–925. https://doi.org/10.56499/jppres23.1657_11.5.902
References

Aslan A, Aslan C, Zolbanin NM, Jafari R (2021) Acute respiratory distress syndrome in COVID-19: Possible mechanisms and therapeutic management. Pneumonia. 13: 14. https://doi.org/10.1186/s41479-021-00092-9

Bleilevens C, Soppert J, Hoffmann A, Breuer T, Bernhagen J, Martin L, Stiehler L, Marx G, Dreher M, Stoppe C, Simon TP (2021) Macrophage migration inhibitory factor (MIF) plasma concentration in critically ill COVID-19 patients: A prospective observational study. Diagnostics (Basel) 11(2): 332. https://doi.org/10.3390/diagnostics11020332

Donnelly S, Haslett C, Reid PT, Grant IS, Wallace WAH, Metz CN, Bruce LJ, Bucala R (1997) Regulatory role for macrophage migration inhibitory factor in acute respiratory distress syndrome. Nat Med 3: 320–323. https://doi.org/10.1038/nm0397-320

Gao L, Flores C, Fan-Ma S, Miller EJ, Moitra J, Moreno L, Wadgaonkar R, Simon B, Brower R, Sevransky J, Tuder RM, Maloney JP, Moss M, Shanholtz C, Yates CR, Meduri GU, Ye SQ, Barnes KC, Garcia JG (2007) Macrophage migration inhibitory factor in acute lung injury: Expression, biomarker, and associations. Transl Res 150(1): 18–29. https://doi.org/10.1016/j.trsl.2007.02.007

Kesuma D, Kirtishanti A, Makayasa CHA, Sumartha IGA (2023) Anticancer activity of N-(4-t-butylbenzoyl)-N’-phenylthiourea: Molecular docking, synthesis, and cytotoxic activity in breast and cervical cancer cells. J Pharm Pharmacogn Res 11(2): 208–215. https://doi.org/10.56499/jppres22.1508_11.2.208

 Kesuma D, Putra GS, Yuniarta TA.(2022a). Synthesis and cytotoxic activity of N-(2,4-dichloro)benzoyl-N’- phenylthiourea against human breast cancer cell line. Thai J Pharm Sci 46(2): 173–176.

Kesuma D, Siswandono, Purwanto BT, Rudyanto M (2020) Synthesis and anticancer evaluation of N-benzoyl-N’-phenyltiourea derivatives against human breast cancer cells (T47D). J Chin Pharm Sci 29(2): 123–129. https://doi.org/10.5246/jcps.2020.02.010

Kesuma D, Siswandono, Kirtishanti A (2022b) Molecular docking and biological activity of n-(4-methoxy)-benzoyl-n’-phenylthiourea and n-(4-trifluoro)-benzoyl-n’-phenylthiourea as anti-breast cancer candidates. Rasayan J Chem 15(2): 1503–1508. https://doi.org/10.31788/RJC.2022.1526836

Kesuma D, Makayasa CHA, Suhud F, Azminah A, Yuniarta TA, Sumartha I, Risthanti RR, Dani FF (2022c) Structure modification: Effect of lipophilic, electronic, and steric parameters of n-benzoyl-n’-phenylthiourea compounds on antiviral activity of COVID-19 by in silico. Rasayan J Chem 15(2): 1445–1449. http://doi.org/10.31788/RJC.2022.1526809

Kok T, Wasiel AA, Dekker FJ, Poelarends GJ, Cool RH (2018) High yield production of human invariant chain CD74 constructs fused to solubility-enhancing peptides and characterization of their MIF-binding capacities. Protein Expr Purif 148: 46–53. http://doi.org/10.1016/j.pep.2018.03.008

Kruger NJ (2002) The Bradford Method for Protein Quantitation. In: Walker JM (eds). The Protein Protocols Handbook. Springer Protocols Handbooks. Humana Press, pp. 15–22. http://doi.org/10.1385/1-59259-169-8:15

Lubetsky JB, Dios A, Han J, Aljabari B, Ruzsicska B, Mitchell R, Lolis E, Al-Abed Y (2002) The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents. J Biol Chem 277(28): 24976–24982. http://doi.org/10.1074/jbc.M203220200

NIH (2021) COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/

Putra GS, Widiyana AP, Muchlashi LA, Sulistyowati MI, Ekowati J, Budiati T (2017) The influence of ratio pyridine and triethylamine catalysts on synthesis 2-phenyl-benzo [D][1, 3] oxazine-4-on derivatives. J Chem Pharm Res 8(1): 73–80.

Turk FE, Fauvet B, Sakouhi HO, Lugari A, Betzi S, Roche P, Morelli X, Lashuel HA (2010) An integrative in silico methodology for the identification of modulators of macrophage migration inhibitory factor (MIF) tautomerase activity. Bioorg Med Chem 18: 5425–5440. https://doi.org/10.1016/j.bmc.2010.05.010

WHO (2020). Corticosteroids for COVID-19: Living guidance, 2 September 2020

Xiao Z, Fokkens M, Chen D, Kok T, Proietti G, Merkerk RV, Poelarends GJ, Dekker FJ (2020) Structure-activity relationships for binding of 4-substituted triazole-phenols to macrophage migration inhibitory factor (MIF). Eur J Med Chem 186: 1118492. https://doi.org/10.1016/j.ejmech.2019.111849

© 2023 Journal of Pharmacy & Pharmacognosy Research

Research trends of studies on oral cancer risk factors

J. Pharm. Pharmacogn. Res., vol. 11, no. 5, pp. 887-901, Sep-Oct 2023.

DOI: https://doi.org/10.56499/jppres23.1712_11.5.887

Review

Risk factors for oral cancer: Thematic trends and research agenda

[Factores de riesgo del cáncer oral: Tendencias temáticas y agenda de investigación]

Orlando Pérez-Delgado1, Pablo Alejandro Millones-Gómez2, Alejandro Valencia-Arias3*, David Yeret Rodríguez-Salazar4

1Laboratorio de Investigación en Ciencias de la Salud, Universidad Señor de Sipán, Chiclayo, 14000, Peru.

2Vicerrectoría de Investigación, Universidad Señor de Sipán, Chiclayo, 14000, Peru.

3School of Industrial Engineering, Faculty of Engineering, Architecture and Urbanism, Universidad Señor de Sipán, Chiclayo 14001, Peru.

4Facultad de Ciencias de la Salud, Universidad Señor de Sipán, Chiclayo, 14000, Peru.

*E-mail: valenciajho@crece.uss.edu.pe

Abstract

Context: Oral cancer is difficult to define due to several factors. It’s known as oral squamous cell carcinoma (OSCC) and is common in the head and neck. Geographic variations in the impact of OSCC highlight the need for research on risk factors and treatment trends.

Aims: To identify the main research trends of studies on oral cancer risk factors in the scientific literature in the Scopus database and Web of Science.

Methods: This was an exploratory study of the risk factors for oral cancer designed considering the eligibility criteria defined by the PRISMA-2020 international statement, that is, inclusion and exclusion.

Results: A total of 215 documents from Scopus and Web of Science were subjected to bibliometric analysis. The years 2020 and 2021 were the most productive, with 18 and 22 articles, respectively. The leading author in productivity and impact was Johnson N, the leading journal was Oral Oncology, followed by the International Journal of Cancer, and the main contributing countries were the United States, the United Kingdom and India. The main thematic cluster was composed of concepts such as Tobacco and Alcohol as the major risk factors; concepts such as Mortality or Head and Neck were positioned as emerging within the scientific literature.

Conclusions: The main risk factors, i.e., alcohol and tobacco consumption, are relevant in terms of mortality in the consumer population, which is why their role should be determined in future studies.

Keywords: malignancy neoplasms; mortality; mouth neoplasms; oral cancer; risk factors; tobacco.

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Resumen

Contexto: El cáncer oral es difícil de definir debido a varios factores. Se conoce como carcinoma oral de células escamosas (CCEO) y es frecuente en la cabeza y el cuello. Las variaciones geográficas en el impacto del CCEO ponen de manifiesto la necesidad de investigar los factores de riesgo y las tendencias de tratamiento.

Objetivos: Identificar las principales tendencias de investigación de los estudios sobre los factores de riesgo del cáncer oral en la literatura científica de la base de datos Scopus y Web of Science.

Métodos: Se trató de un estudio exploratorio de los factores de riesgo de cáncer oral diseñado considerando los criterios de elegibilidad definidos por la declaración internacional PRISMA-2020, es decir, inclusión y exclusión.

Resultados: Un total de 215 documentos de Scopus y Web of Science fueron sometidos a análisis bibliométrico. Los años 2020 y 2021 fueron los más productivos, con 18 y 22 artículos, respectivamente. El autor líder en productividad e impacto fue Johnson N, la revista líder fue Oral Oncology, seguida de International Journal of Cancer, y los principales países contribuyentes fueron Estados Unidos, Reino Unido e India. El principal cluster temático estuvo compuesto por conceptos como Tabaco y Alcohol como principales factores de riesgo; conceptos como Mortalidad o Cabeza y Cuello se posicionaron como emergentes dentro de la literatura científica.

Conclusiones: Los principales factores de riesgo, es decir, el consumo de alcohol y tabaco, son relevantes en términos de mortalidad en la población consumidora, por lo que su papel debería determinarse en futuros estudios.

Palabras Clave: neoplasias malignas; mortalidad; neoplasias bucales; cáncer oral; factores de riesgo; tabaco.

jppres_pdf_free
Citation Format: Pérez-Delgado O, Millones-Gómez PA, Valencia-Arias A, Rodríguez-Salazar DY (2023) Risk factors for oral cancer: Thematic trends and research agenda. J Pharm Pharmacogn Res 11(5): 887–901. https://doi.org/10.56499/jppres23.1712_11.5.887
References

Ahmad P, Nawaz R, Qurban M, Shaikh GM, Mohamed RN, Nagarajappa AK, Asif JA, Alam MK (2021) Risk factors associated with the mortality rate of oral squamous cell carcinoma patients: A 10-year retrospective study. Medicine (Baltimore) 100: e27127. https://doi.org/10.1097/md.0000000000027127

Akinkugbe AA, Garcia DT, Brickhouse TH, Mosavel M (2020) Lifestyle risk factor related disparities in oral cancer examination in the U.S: A population-based cross-sectional study. BMC Public Health 20: 153. https://doi.org/10.1186/s12889-020-8247-2

Amarasinghe HK, Usgodaarachchi US, Johnson NW, Lalloo R, Warnakulasuriya S (2010) Public awareness of oral cancer, of oral potentially malignant disorders and of their risk factors in some rural populations in Sri Lanka. Community Dent Oral Epidemiol 38: 540–548. https://doi.org/10.1111/j.1600-0528.2010.00566.x

Anwar N, Pervez S, Chundriger Q, Awan S, Moatter T, Ali TS (2020) Oral cancer: Clinicopathological features and associated risk factors in a high risk population presenting to a major tertiary care center in Pakistan. PLoS One 15: e0236359. https://doi.org/10.1371/journal.pone.0236359

Ariyawardana A, Sitheeque MA, Ranasinghe AW, Perera I, Tilakaratne WM, Amaratunga EA, Yang YH, Warnakulasuriya S (2007) Prevalence of oral cancer and pre-cancer and associated risk factors among tea estate workers in the central Sri Lanka. J Oral Pathol Med 36: 581–587. https://doi.org/10.1111/j.1600-0714.2007.00583.x

Capote-Moreno A, Brabyn P, Muñoz-Guerra MF, Sastre-Pérez J, Escorial-Hernandez V, Rodríguez-Campo FJ, García T, Naval-Gías L (2020) Oral squamous cell carcinoma: Epidemiological study and risk factor assessment based on a 39-year series. Int J Oral Maxillofac Surg 49: 1525–1534. https://doi.org/10.1016/j.ijom.2020.03.009

Cariati P, Ozan D, Corcóles C, Tursun R, Rodríguez S (2021) Risk factors for distant metastasis in oral cancer and a strategy preoperative detection. Front Oral Maxillofac Med 3: 24. https://doi.org/10.21037/fomm-21-13

Chen KJ, Hsieh MH, Lin YY, Chen MY, Lien MY, Yang SF, Tang CH (2022) Visfatin polymorphisms, lifestyle risk factors and risk of oral squamous cell carcinoma in a cohort of Taiwanese males. Int J Med Sci 19: 762–768. https://doi.org/10.7150/ijms.69868

Chen TC, Lou PJ, Ko JY, Yang TL, Chang YL, Wang CP (2013) Treatment outcomes in pT4aN0 oral squamous cell carcinoma patients without pathological risk factors. Head Neck Oncol 5: 45.

Cheong SC, Chandramouli GV, Saleh A, Zain RB, Lau SH, Sivakumaren S, Pathmanathan R, Prime SS, Teo SH, Patel V (2009) Gene expression in human oral squamous cell carcinoma is influenced by risk factor exposure. Oral Oncol 45: 712–719. https://doi.org/10.1016/j.oraloncology.2008.11.002

Chuang ST, Chen CC, Yang SF, Chan LP, Kao YH, Huang MY, Tang JY, Huang CM, Huang CJ (2020) Tumor histologic grade as a risk factor for neck recurrence in patients with T1-2N0 early tongue cancer. Oral Oncol 106: 104706. https://doi.org/10.1016/j.oraloncology.2020.104706

Conway DI, Purkayastha M, Chestnutt IG (2018) The changing epidemiology of oral cancer: Definitions, trends, and risk factors. Br Dent J 225: 867–873. https://doi.org/10.1038/sj.bdj.2018.922

Fu G, Wang C, Zeng C, Liu Z, Han Z, Huang H, Cao M (2022) Perioperative risk factors associated with unplanned reoperation following vascularised free flaps reconstruction of the oral squamous cell carcinoma. J Craniofac Surg 33: 2507–2512. https://doi.org/10.1097/scs.0000000000008762

Hasegawa T, Yanamoto S, Otsuru M, Yamada SI, Minamikawa T, Shigeta T, Naruse T, Suzuki T, Sasaki M, Ota Y (2017) Retrospective study of treatment outcomes after postoperative chemoradiotherapy in Japanese oral squamous cell carcinoma patients with risk factors of recurrence. Oral Surg Oral Med Oral Pathol Oral Radiol 123: 524–530. https://doi.org/10.1016/j.oooo.2016.11.014

Hasegawa T, Yatagai N, Furukawa T, Wakui E, Saito I, Takeda D, Kakei Y, Sakakibara A, Nibu KI, Akashi M (2021) The prospective evaluation and risk factors of dysphagia after surgery in patients with oral cancer. J Otolaryngol Head Neck Surg 50: 4. https://doi.org/10.1186/s40463-020-00479-6

Herrera-Serna BY, Lara-Carrillo E, Toral-Rizo VH, Do Amaral RC (2019) Effect of risk factor control policies on oral cancer mortality in Latin America. Rev Esp Salud Publica 93: 201907050. https://pubmed.ncbi.nlm.nih.gov/31328723/

Johnson NW, Gupta B, Ariyawardana A, Amarasinghe H (2017) Epidemiology and site-specific risk factors for oral cancer. In Kuriakose MA (Ed.), Contemporary Oral Oncology: Biology, Epidemiology, Etiology, and Prevention. Springer International Publishing, pp. 103–153. https://doi.org/10.1007/978-3-319-14911-0_4

Krishna A, Singh RK, Singh S, Verma P, Pal US, Tiwari S (2014) Demographic risk factors, affected anatomical sites and clinicopathological profile for oral squamous cell carcinoma in a north Indian population. Asian Pac J Cancer Prev 15: 6755–6760. https://doi.org/10.7314/apjcp.2014.15.16.6755

Li Y, Liu K, Ke Y, Zeng Y, Chen M, Li W, Liu W, Hua X, Li Z, Zhong Y (2019) Risk factors analysis of pathologically confirmed cervical lymph nodes metastasis in oral squamous cell carcinoma patients with clinically negative cervical lymph node: Results from a cancer center of central China. J Cancer 10: 3062–3069. https://doi.org/10.7150/jca.30502

Llewellyn CD, Johnson NW, Warnakulasuriya KA (2004) Risk factors for oral cancer in newly diagnosed patients aged 45 years and younger: A case-control study in Southern England. J Oral Pathol Med 33: 525–532. https://doi.org/10.1111/j.1600-0714.2004.00222.x

Mehdi RF, Sheikh F, Khan R, Fawad B, Haq AU (2019) Survivin promoter polymorphism (-31 C/G): A genetic risk factor for oral cancer. Asian Pac J Cancer Prev 20: 1289–1293. https://doi.org/10.31557/apjcp.2019.20.4.1289

Mejía OJP, Arias MCM, Echeverri SLC (2017) El papel de la educación en creación de empresas en el contexto universitario a partir de los estudios registrados en Scopus. Rev CEA 3: 69–87. https://doi.org/10.22430/24223182.651

Merchant A, Husain SS, Hosain M, Fikree FF, Pitiphat W, Siddiqui AR, Hayder SJ, Haider SM, Ikram M, Chuang SK (2000) Paan without tobacco: an independent risk factor for oral cancer. Int J Cancer 86: 128–131. https://doi.org/10.1002/(sici)1097-0215(20000401)86:1

Miller CS, Johnstone BM (1982) Human papillomavirus as a risk factor for oral squamous cell carcinoma: A meta-analysis. Oral Med Oral Pathol Oral Radiol Endod 91: 622–635. https://doi.org/10.1067/moe.2001.115392

Monaharan S, Nagini S (1995) Risk factors alter glycloprotein levels in oral cancer patients. Med Sci Res 23: 229–230.

Mukherjee A, Bhowmick C, Chattopadhyay S, Kathar MA, Bhattacharyya M, Nasreen S, Jain P, Arun P, Datta SS (2022) Preoperative risk factors associated with peri-operative psychiatric diagnosis in oral cancer patients. Ecancermedicalscience 16: 1401. https://doi.org/10.3332/ecancer.2022.1401

Neckel N, Michael M, Troeltzsch D, WÜster J, Koerdt S, Doll C, Jöhrens K, Neumann K, Heiland M, Raguse JD (2020) Rediscussing the role of traditional risk factors in young adults with oral squamous cell carcinoma. Anticancer Res 40: 6987–6995. https://doi.org/10.21873/anticanres.14723

Pranckutė R (2021) Web of Science (WoS) and Scopus: The titans of bibliographic information in today’s academic world. Publications 9: 12. https://doi.org/10.3390/publications9010012

Sarkis-Onofre R, Catalá-López F, Aromataris E, Lockwood C (2021) How to properly use the PRISMA statement. Syst Rev 10: 117. https://doi.org/10.1186/s13643-021-01671-z

Soutome S, Yanamoto S, Nishii M, Kojima Y, Hasegawa T, Funahara M, Akashi M, Saito T, Umeda M (2021) Risk factors for severe radiation-induced oral mucositis in patients with oral cancer. J Dent Sci 16: 1241–1246. https://doi.org/10.1016/j.jds.2021.01.009

Subash A, Bylapudi B, Thakur S, Rao V U S (2022) Oral cancer in India, a growing problem: Is limiting the exposure to avoidable risk factors the only way to reduce the disease burden? Oral Oncol 125: 105677. https://doi.org/10.1016/j.oraloncology.2021.105677

Tenore G, Nuvoli A, Mohsen A, Cassoni A, Battisti A, Terenzi V, Della Monaca M, Raponi I, Brauner E, Felice F (2020) Tobacco, alcohol and family history of cancer as risk factors of oral squamous cell carcinoma: Case-control retrospective study. Appl Sci 10: 3896. https://doi.org/10.3390/app10113896

Thakar A, Thakur R, Kakkar A, Malhotra RK, Singh CA, Sikka K, Kumar R, Pramanik R, Biswas A, Bhalla AS (2021) Oral cancer in the Indian subcontinent-survival outcomes and risk factors with primary surgery. Laryngoscope 131: 2254–2261. https://doi.org/10.1002/lary.29537

Tsai YD, Wang CP, Chen CY, Lin LW, Lin TM, Hsu CC, Chung FM, Lin HC, Hsu HF, Lee YJ (2013) Elevated plasma level of visfatin/pre-b cell colony-enhancing factor in male oral squamous cell carcinoma patients. Med Oral Patol Oral Cir Bucal 18: 180–186. https://doi.org/10.4317/medoral.18574

Yang Y, Zhou M, Zeng X, Wang C (2021) The burden of oral cancer in China, 1990-2017: An analysis for the global burden of disease, injuries, and risk factors study 2017. BMC Oral Health 21: 44. https://doi.org/10.1186/s12903-020-01386-y

Zhu S, Zhang F, Zhao G, Zhang X, Zhang X, Li T, Hu C, Zhu W, Li D (2022) Trends in the global burden of oral cancer joint with attributable risk factors: Results from the global burden of disease study 2019. Oral Oncol 134: 106189. https://doi.org/10.1016/j.oraloncology.2022.106189

© 2023 Journal of Pharmacy & Pharmacognosy Research

Vitis gracilis, spermatozoa and maximal exercise

J. Pharm. Pharmacogn. Res., vol. 11, no. 5, pp. 874-886, Sep-Oct 2023.

DOI: https://doi.org/10.56499/jppres23.1685_11.5.874

Original Article

Improvement of spermatozoa concentration due to maximal exercise with Vitis gracilis Wall.

[Mejoría de la concentración de espermatozoides por ejercicio máximo con Vitis gracilis Wall.]

Syafruddin Ilyas1*, Putra Santoso2, Yurnadi Hanafi Midoen3, Putri Cahaya Situmorang1

1Study program of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, Indonesia.

2Department of of Biology, Faculty of Mathematics and Natural Sciences, Universitas Andalas, Padang, Indonesia.

3Department of Medical Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

*E-mail: syafruddin6@usu.ac.id

Abstract

Context: Swimming is a common form of exercise; however, excessive exercise might reduce sperm count by lowering testosterone levels and increasing the production of free radicals, commonly known as reactive oxygen species (ROS). In Indonesia, Vitis gracilis Wall. is a traditional remedy for increasing stamina.

Aims: To assess the concentration of spermatozoa after vigorous physical activity and V. gracilis administration, as well as the histological and apoptotic changes in testicular histology that occur via caspase-3 expression.

Methods: This study was conducted on six groups of rats: the control group (G+), a group of rats subjected to vigorous swimming then administered 0.2 mg/kg BW vit C (GVitC), and three groups of rats subjected to vigorous swimming then administered 100, 125, or 150 mg/kg BW V. gracilis (G100, G125, and G150). Testicular tissue and blood serum samples were extracted from the rats subjected to vigorous swimming. Testicular tissue was immunohistochemically stained using caspase-3 antibody and TUNEL assays, while blood samples were analysed using ELISA.

Results: V. gracilis administration significantly affected IL-6 and testosterone levels (p<0.00). Testosterone had a greater impact on spermatozoa concentration than IL-6. Caspase-3 expression and the proportion of apoptotic cells were both markedly reduced.

Conclusions: Administering 125 mg/kg BW V. gracilis can help to increase sperm concentration by reducing apoptosis through altering caspase-3 and IL-6 levels, thereby preventing inflammation. This plant might be a viable molecular therapeutic target for staminal medicines.

Keywords: IL-6; overexercise; sperm; testosterone; Vitis gracilis.

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Resumen

Contexto: La natación es una forma común de ejercicio; sin embargo, el ejercicio excesivo podría reducir el recuento de espermatozoides al disminuir los niveles de testosterona y aumentar la producción de radicales libres, comúnmente conocidos como especies reactivas del oxígeno (ROS). En Indonesia, Vitis gracilis Wall. es un remedio tradicional para aumentar la resistencia.

Objetivos: Evaluar la concentración de espermatozoides tras una actividad física vigorosa y la administración de V. gracilis, así como los cambios histológicos y apoptóticos en la histología testicular que se producen a través de la expresión de caspasa-3.

Métodos: Este estudio se llevó a cabo en seis grupos de ratas: el grupo de control (G+), un grupo de ratas sometidas a natación vigorosa y luego administradas 0,2 mg/kg BW vit C (GVitc), y tres grupos de ratas sometidas a natación vigorosa y luego administradas 100, 125 o 150 mg/kg BW V. gracilis (G100, G125 y G150). Se extrajeron muestras de tejido testicular y suero sanguíneo de las ratas sometidas a natación vigorosa. El tejido testicular se tiñó inmunohistoquímicamente con el anticuerpo caspasa-3 y se realizaron ensayos TUNEL, mientras que las muestras de sangre se analizaron mediante ELISA.

Resultados: La administración de V. gracilis afectó significativamente a los niveles de IL-6 y testosterona (p<0,00). La testosterona tuvo un mayor impacto en la concentración de espermatozoides que la IL-6. La expresión de caspasa-3 y la proporción de células apoptóticas se redujeron notablemente.

Conclusiones: La administración de 125 mg/kg BW de V. gracilis puede ayudar a aumentar la concentración de espermatozoides mediante la reducción de la apoptosis a través de la alteración de los niveles de caspasa-3 e IL-6, previniendo así la inflamación. Esta planta podría ser una diana terapéutica molecular viable para medicamentos estaminales.

Palabras Clave: esperma; IL-6; sobreesfuerzo; testosterona; Vitis gracilis.

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Citation Format: Ilyas S, Santoso P, Midoen YH, Situmorang PC (2023) Improvement of spermatozoa concentration due to maximal exercise with Vitis gracilis Wall. J Pharm Pharmacogn Res 11(5): 874–886. https://doi.org/10.56499/jppres23.1685_11.5.8743
References

Alahmar AT (2019) Role of oxidative stress in male infertility: An updated review. J Hum Reprod Sci 12(1): 4–18. https://doi.org/10.4103/jhrs.JHRS_150_18

Aththorick TA, Berutu L (2018) Ethnobotanical study and phytochemical screening of medicinal plants on Karonese people from North Sumatra, Indonesia. J Phys Conf Ser 11169(5): 052008. https://doi.org/10.1088/1742-6596/1116/5/052008

Babakhanzadeh E, Nazari M, Ghasemifar S, Khodadadian A (2020) Some of the factors involved in male infertility: A prospective review. Int J Gen Med 13: 29–41. https://doi.org/10.2147/IJGM.S241099

Bhagya KP, Aswathy RJ, Radhakrishnan K, Sengottaiyan J, Kumar PG (2020) Autoimmune regulator enhanced the expression of caspase-3 and did not induce massive germ cell apoptosis in GC1-Spg cells. Cell Physiol Biochem 54(1): 40–52. https://doi.org/10.33594/000000204

Darbandi M, Darbandi S, Agarwal A, Sengupta P, Durairajanayagam D, Henkel R, Sadeghi MR (2018) Reactive oxygen species and male reproductive hormones. Reprod Biol Endocrin 16(1):87. https://doi.org/10.1186/s12958-018-0406-2

Docherty S, Harley R, McAuley JJ, Crowe LAN, Pedret C, Kirwan PD, Siebert S, Millar NL (2022) The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review. BMC Sports Sci Med Rehabil 14(1): 5. https://doi.org/10.1186/s13102-022-00397-2

Dominiak K, Jarmuszkiewicz W (2021) The Relationship between mitochondrial reactive oxygen species production and mitochondrial energetics in rat tissues with different contents of reduced coenzyme Q. Antioxidants (Basel) 10(4): 533. https://doi.org/10.3390/antiox10040533

Ernawati, I’tishom R, Sudjarwo SA (2019) The signal transduction of xanthone as a protector on 2-methoxyethanol-induced cardiac cell damage in mice. J Adv Pharm Technol Res 10(4): 184–189. https://doi.org/10.4103/japtr.JAPTR_57_19

Gunter NV, The SS, Lim YM, Mah SH (2020) Natural xanthones and skin inflammatory diseases: Multitargeting mechanisms of action and potential application. Front Pharmacol 11: 594202. https://doi.org/10.3389/fphar.2020.594202

Hirata Y (2019) Reactive oxygen species (ROS) signaling: Regulatory mechanisms and pathophysiological roles. [Japanese]. Yakugaku Zasshi 139(10): 1235-1241. https://doi.org/10.1248/yakushi.19-00141

Ilyas S, Hutahaean S, Sinaga RSH, Situmorang PC (2021) Apoptosis via cytochrome c in aortic tissue of diabetes mellitus after giving sikkam leaves (Bischofia javanica Blume). J Pharm Pharmacogn Res 9(3): 313–323. https://doi.org/10.56499/jppres20.967_9.3.313

Ilyas S, Hutahaean S, Sinaga RSH, Situmorang PC (2022) Effect of sikkam (Bischofia javanica Blume) ethanolic extract on the quality and quantity of hyperglycemic rat sperm. J Pharm Pharmacogn Res 10(2): 270–278. https://doi.org/10.56499/jppres21.1204_10.2.270

Jóźków P, Rossato M (2017) The impact of intense exercise on semen quality. Am J Mens Health 11(3): 654–662. https://doi.org/10.1177/1557988316669045

Kausar S, Wang F, Cui H (2018) The role of mitochondria in reactive oxygen species generation and its implications for neurodegenerative diseases. Cells 7(12): 274. https://doi.org/10.3390/cells7120274

Kolar MJ, Konduri S, Chang T, Wang H, McNerlin C, Ohlsson L, Härröd M, Siegel D, Saghatelian A (2019) Linoleic acid esters of hydroxy linoleic acids are anti-inflammatory lipids found in plants and mammals. J Biol Chem 294(27): 10698–10707. https://doi.org/10.1074/jbc.RA118.006956

Krüger K, Frost S, Most E, Völker K, Pallauf J, Mooren FC (2009) Exercise affects tissue lymphocyte apoptosis via redox-sensitive and Fas-dependent signaling pathways. Am J Physiol Regul Integr Comp Physiol 296(5): R1518–R1527. https://doi.org/10.1152/ajpregu.90994.2008

Kumar N, Singh AK (2015) Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci 8(4): 191–196. https://doi.org/10.4103/0974-1208.170370

Lahart IM, Metsios GS (2018) Chronic physiological effects of swim training interventions in non-elite swimmers: A systematic review and meta-analysis. Sports Med 48(2): 337–359. https://doi.org/10.1007/s40279-017-0805-0

Lincho J, Martins RC, Gomes J (2021) Paraben compounds—Part I: An overview of their characteristics, detection, and impacts. Appl Scis 11(5): 2307. https://doi.org/10.3390/app11052307

Malca-García GR, Hennig L, Ganoza-Yupanqui MY, Piña-Iturbe A, Bussmann RW (2017) Constituents from the bark resin of Schinus molle. Rev Bras Farmacogn 27(1): 67–69. https://doi.org/10.1016/j.bjp.2016.07.004

Mannucci A, Argento FR, Fini E, Coccia ME, Taddei N, Becatti M, Fiorillo C (2022) The impact of oxidative stress in male infertility. Front Mol Biosci 8: 799294. https://doi.org/10.3389/fmolb.2021.799294

Manurung RD, Ilyas S, Hutahaean S, Rosidah R, Situmorang PC (2021) Diabetic wound healing in FGF expression by nano herbal of Rhodomyrtus tomentosa L. and Zanthoxylum acanthopodium fruits. Pak J Biol Sci 24(3): 401–408. https://doi.org/10.3923/pjbs.2021.401.408

Martin LJ, Touaibia M (2020) Improvement of testicular steroidogenesis using flavonoids and isoflavonoids for prevention of late-onset male hypogonadism. Antioxidants (Basel) 9(3): 237. https://doi.org/10.3390/antiox9030237

Midoen YH, Ilyas S, Santoso P, Situmorang PC (2023) Effect of maximal physical exercise on apoptosis via cytochrome c in hippocampus cells after administration of Vitis gracilis Wall. J Pharm Pharmacogn Res 11(2): 297–307. https://doi.org/10.56499/jppres22.1563_11.2.297

Mooren FC, Krüger K (2015) Exercise, autophagy, and apoptosis. Prog Mol Biol Transl Sci 135: 407–422. https://doi.org/10.1016/bs.pmbts.2015.07.023

Oduwole OO, Huhtaniemi IT, Misrahi M (2021) The roles of luteinizing hormone, follicle-stimulating hormone and testosterone in spermatogenesis and folliculogenesis revisited. Int J Mol Sci 22(23): 12735. https://doi.org/10.3390/ijms222312735

Phaneuf S, Leeuwenburgh C (2001) Apoptosis and exercise. Med Sci Sports Exer 33(3): 393–396. https://doi.org/10.1097/00005768-200103000-00010

Ramírez ND, Luque EM, Jones XM, Torres PJ, Moreira Espinoza MJ, Cantarelli V, Ponzio MF, Arja A, Rabaglino MB, Martini AC (2019) Modulatory effects of ghrelin on sperm quality alterations induced by a fructose-enriched diet. Heliyon 5(11): e02886. https://doi.org/10.1016/j.heliyon.2019.e02886

Redza-Dutordoir M, Averill-Bates DA (2016) Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta Mol Cell Res 1863(12): 2977–2992. https://doi.org/10.1016/j.bbamcr.2016.09.012

Riachy R, McKinney K, Tuvdendorj DR (2020) Various factors may modulate the effect of exercise on testosterone levels in men. J Funct Morphol Kinesio 5(4): 81. https://doi.org/10.3390/jfmk5040081

Sabeti P, Pourmasumi S, Rahiminia T, Akyash F, Talebi AR (2016) Etiologies of sperm oxidative stress. Int J Reprod Biomed 14(4): 231–240. https://pubmed.ncbi.nlm.nih.gov/27351024

Sahlin K, Shabalina IG, Mattsson CM, Bakkman L, Fernström M, Rozhdestvenskaya Z, Enqvist JK, Nedergaard J, Ekblom B, Tonkonogi M (2010) Ultraendurance exercise increases the production of reactive oxygen species in isolated mitochondria from human skeletal muscle. J Appl Physiol 108(4): 780–787. https://doi.org/10.1152/japplphysiol.00966.2009

Santoso P, Ilyas S, Midoen YH, Situmorang PC (2023) Effect of Vitis gracilis Wall. administration on maximal swimming exercise apoptosis via cytochrome c in rat lung cells. J Pharm Pharmacogn Res 11(3): 381–390. https://doi.org/10.56499/jppres23.1603_11.3.381

Simanullang RH, Situmorang PC, Herlina M, Noradina, Silalahi B (2022b) Cytochrome c expression by andaliman (Zanthoxylum acanthopodium) on cervical cancer histology. Pak J Biol Sci 25(1): 49–55. https://doi.org/10.3923/pjbs.2022.49.55

Simanullang RH, Situmorang PC, Herlina M, Noradina, Silalahi B, Manurung SS (2022a) Histological changes of cervical tumours following Zanthoxylum acanthopodium DC treatment, and its impact on cytokine expression. Saudi J Biol Sci 29(4): 2706–2718. https://doi.org/10.1016/j.sjbs.2021.12.065

Situmorang PC, Ilyas S, Hutahaean S, Rosidah R (2021) Histological changes in placental rat apoptosis via FasL and cytochrome c by the nano-herbal Zanthoxylum acanthopodium. Saudi J Biol Sci 28(5): 3060–3068. https://doi.org/10.1016/j.sjbs.2021.02.047

Situmorang PC, Simanullang RH, Syahputra RA, Hutahaean MM, Sembiring H, Nisfa L, Sari ER (2023) Histological analysis of TGFβ1 and VEGFR expression in cervical carcinoma treated with Rhodomyrtus tomentosa. Pharmacia 70(1): 217–223. https://doi.org/10.3897/pharmacia.70.e96811

Tanaka T, Narazaki M, Kishimoto T (2014) IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 6(10): a016295. https://doi.org/10.1101/cshperspect.a016295

Vingren JL, Kraemer WJ, Ratamess] NA, Anderson JM, Volek JS, Maresh CM (2010) Testosterone physiology in resistance exercise and training: The up-stream regulatory elements. Sports Med 40(12): 1037–1053. https://doi.org/10.2165/11536910-000000000-00000

Wasnis NZ, Ilyas S, Hutahaean S, Silaban R, Situmorang PC (2022) Effect of Vitis gracilis Wall (gagatan harimau) in the recovery of gastrocnemius muscle cells and cytochrome c expression of Mus musculus. J Pharm Pharmacogn Res 10(2): 303–309. https://doi.org/10.56499/jppres21.1208_10.2.303

Wischmann T, Thorn P (2013) (Male) infertility: what does it mean to men? New evidence from quantitative and qualitative studies. Reprod Biomed Online 27(3): 236–243. https://doi.org/10.1016/j.rbmo.2013.06.002

Yamakawa T, Ishida K, Kato S, Kodama T, Minoda Y (1983) Formation and identification of anthocyanins in cultured cells of Vitis sp. Agric Biol Chem 47(5): 997–1001. https://doi.org/10.1080/00021369.1983.10865764

© 2023 Journal of Pharmacy & Pharmacognosy Research

Antimalarial and toxicology of Andrographis paniculata tablet

J. Pharm. Pharmacogn. Res., vol. 11, no. 5, pp. 863-873, Sep-Oct 2023.

DOI: https://doi.org/10.56499/jppres23.1679_11.5.863

Original Article

Antimalarial and toxicological assessment of the tablet (AS201-01) ethyl acetate fraction of Andrographis paniculata Nees in animal models

[Evaluación antimalárica y toxicológica de fracción de acetato de etilo del comprimido (AS201-01) de Andrographis paniculata Nees en modelos animales]

Aty Widyawaruyanti1,2*, Hilkatul Ilmi2, Lidya Tumewu2, Dwi Ayu Fitrianingtyas3, Yesinta Kurniawati3, Alfin Laila Najiha3, Hanifah Khairun Nisa2, Che Puteh Osman4,5, Nor Hadiani Ismail4,5, Achmad Fuad Hafid1,2

1Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, Indonesia.

2Center for Natural Product Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, 60115, Indonesia.

3Undergraduate Program of Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia.

4Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Cawangan Selangor, Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor Malaysia.

5Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia.

*E-mail: aty-w@ff.unair.ac.id

Abstract

Context: Andrographis paniculata has been used as a traditional medicine to treat malaria. The ethyl acetate fraction of A. paniculata containing diterpene lactone compounds was developed into a tablet dosage form, AS201-01.

Aims: To determine the antimalarial activity and toxicity of AS201-01 to guarantee its efficacy and safety.

Methods: Antimalarial assay in male Balb/c mice based on Peter’s four-day suppressive test at a dose of 6.25, 12.5, 25, and 50 mg/kg BW and 10 mg/kg BW of chloroquine as a positive control. In acute toxicity, AS201-01 was administered orally at a dose of 5, 50, 200, and 2,000 mg/kg BW in male rats (Wistar rats) and observed for 14 days to identify signs of toxicity and mortality. Meanwhile, AS201-01 was administered at 50, 327, and 1,000 mg/kg BW per day for 28 days in male and female rats to assess subchronic toxicity.

Results: AS201-01 has antimalarial activity and exhibited the highest suppressive effect at 50 mg/kg BW dose with inhibition of 73.48%. Meanwhile, chloroquine at 10 mg/kg BW has an inhibition of 97.94%. AS201-01 was highly active as an antimalarial with an ED50 value of 5.95 mg/kg BW and increased survival time. Administration of AS201-01 is relatively safe in acute and subchronic toxicity studies. No clinical signs and mortality were observed in either study. The 50% lethal dose (LD50) was above 2,000 mg/kg BW.

Conclusions: AS201-01 is effective as an antimalarial and non-toxic when administered orally at an equivalent therapeutic dose in an animal model.

Keywords: acute toxicity; Andrographis paniculate; antimalarial; subchronic toxicity; medicine.

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Resumen

Contexto: Andrographis paniculata se ha utilizado como medicina tradicional para tratar la malaria. La fracción de acetato de etilo de A. paniculata que contiene compuestos de lactona diterpénica se desarrolló en una forma de dosificación en comprimidos, AS201-01.

Objetivos: Determinar la actividad antimalárica y la toxicidad de AS201-01 para garantizar su eficacia y seguridad.

Métodos: Ensayo antipalúdico en ratones Balb/c macho basado en la prueba supresora de Peter de cuatro días a dosis de 6,25, 12,5, 25 y 50 mg/kg de peso corporal y 10 mg/kg de peso corporal de cloroquina como control positivo. En toxicidad aguda, el AS201-01 se administró por vía oral a dosis de 5, 50, 200 y 2.000 mg/kg de peso corporal en ratas macho (ratas Wistar) y se observó durante 14 días para identificar signos de toxicidad y mortalidad. Mientras tanto, se administró AS201-01 a 50, 327 y 1.000 mg/kg de peso corporal por día durante 28 días en ratas macho y hembra para evaluar la toxicidad subcrónica.

Resultados: AS201-01 tiene actividad antipalúdica y exhibió el mayor efecto supresor con una dosis de 50 mg/kg de peso corporal, con una inhibición del 73,48%. Mientras tanto, la cloroquina a 10 mg/kg de peso corporal tiene una inhibición del 97,94%. AS201-01 fue altamente activo como antimalárico con un valor ED50 de 5,95 mg/kg de peso corporal y aumentó el tiempo de supervivencia. La administración de AS201-01 es relativamente segura en estudios de toxicidad aguda y subcrónica. No se observaron signos clínicos ni mortalidad en ninguno de los dos estudios. La dosis letal al 50% (DL50) fue superior a 2.000 mg/kg de peso corporal.

Conclusiones: AS201-01 es eficaz como antipalúdico y no tóxico cuando se administra por vía oral a una dosis terapéutica equivalente en un modelo animal.

Palabras Clave: Andrographis paniculate; antimalárico; medicamento; toxicidad aguda; toxicidad subcrónica.

jppres_pdf_free
Citation Format: Widyawaruyanti A, Ilmi H, Tumewu L, Fitrianingtyas DA, Kurniawati Y, Najiha AL, Nisa HK, Osman CP, Ismail NH,Hafid AF (2023) Antimalarial and toxicological assessment of the tablet (AS201-01) ethyl acetate fraction of Andrographis paniculata Nees in animal models. J Pharm Pharmacogn Res 11(5): 863–873. https://doi.org/10.56499/jppres23.1679_11.5.863
References

Akbar S (2011) Andrographis paniculata: a review of pharmacological activities and clinical effects. Altern Med Rev 16(1): 66–77.

Alshawsh MA, Mothana RA, Al-shamahy HA, Alsllami SF, Lindequist U (2009) Assessment of antimalarial activity against Plasmodium falciparum and phytochemical screening of some yemeni medicinal plants. Evid Based Complement Altern Med 6(4): 453–456. https://doi.org/10.1093/ecam/nem148

Amat ALS, Ilmi H, Tumewu LT, Notopuro H, Tantular IS, Hafid AF, Widyawaruyanti A (2021) The effect of Andrographis paniculata nees on oxidative stress and parasitemia levels of Plasmodium berghei infected rats. Res J Pharm Technol 14(12): 6676-0. http://dx.doi.org/10.52711/0974-360X.2021.01153

Baker HJ, Lindsey R, Weisbroth SH, editors (1979) The laboratory rat: Biology and diseases. Academic Press. Elsevier Inc.

Bastiana, Widyawaruyanti A, Ilmi H, Tumewu L, Prasetyo B, Hafid AF, Aryati (2022) A tablet derived from Andrographis paniculata complements dihydroartemisinin-piperaquine treatment of malaria in pregnant mice. J Basic Clin Physiol Pharmacol 33(2): 175–183. https://doi.org/10.1515/jbcpp-2020-0162

Chen Y, Wu MX, Liu J, Ma XJ, Shi JL, Wang SN, Zheng ZQ, Guo JY (2018) Acute and sub-acute oral toxicity studies of the aqueous extract from radix, radix with cortex and cortex of Psammosilene tunicoides in mice and rats. J Ethnopharmacol 213: 199–209. http://dx.doi.org/10.1016/j.jep.2017.11.011

Christapher PV, Parasuraman S, Asmawi MZ, Murugaiyah V (2017) Acute and subchronic toxicity studies of methanol extract of Polygonum minus leaves in Sprague Dawley rats. Regul Toxicol Pharmacol 86: 33–41. https://doi.org/10.1016/j.yrtph.2017.02.005

Cui L, Mharakurwa S, Ndiaye D, Rathod PK, Rosenthal PJ (2015) Antimalarial drug resistance: literature review and activities and findings of the ICEMR Network. Am J Trop Med Hyg 93(Suppl 3): 57–68. https://doi.org/10.4269/ajtmh.15-0007

Dua VK, Ojha VP, Roy R, Joshi BC, Valecha N, Devi CU, Bhatnagar MC, Sharma VP, Subbarao SK (2004) Anti-malarial activity of some xanthones isolated from the roots of Andrographis paniculata. J Ethnopharmacol 95(2–3): 247–251. https://doi.org/10.1016/j.jep.2004.07.008

Dwivedi MK, Mishra S, Sonter S, Singh PK (2021) Diterpenoids as potential anti-malarial compounds from Andrographis paniculata. Beni-Suef Univ J Basic Appl Sci 10(1): 7. http://dx.doi.org/10.1186/s43088-021-00098-8

Fidock DA, Rosenthal PJ, Croft SL, Brun R, Nwaka S (2004) Antimalarial drug discovery: Efficacy models for compound screening. Nat Rev Drug Discov 3: 509–520. https://doi.org/10.1038/nrd1416

Ilmi H, Pamungkas IR, Tumewu L, Hafid AF, Widyawaruyanti A (2021) Analgesic and antipyretic activities of ethyl acetate fraction tablet of Andrographis paniculata in animal models. Evid Based Complement Alternat Med 2021: 8848797. https://doi.org/10.1155/2021/8848797

Jaihan U, Srichairatanakool S, Uthaipibull C, Somsak V (2014) Antimalarial effects of methanolic leaf extract of Andrographis paniculata on Plasmodium berghei. J Health Res 28(6): 403–408.

Jarukamjorn K, Nemoto N (2008) Pharmacological aspects of Andrographis paniculata on health and its major diterpenoid constituent andrographolide. J Heal Sci 54(4): 370–381. https://doi.org/10.1248/jhs.54.370

Jayakumar T, Hsieh CY, Lee JJ, Sheu JR (2013) Experimental and clinical pharmacology of Andrographis paniculata and its major bioactive phytoconstituent andrographolide. Evid Based Complement Altern Med 2013: 846740. https://doi.org/10.1155/2013/846740

Liju VB, Jeena K, Kuttan R (2013) Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L). Food Chem Toxicol 53: 52–61. https://doi.org/10.1016/j.fct.2012.11.027

Mengiste B, Mekuria A, Aleme H, Afera B, Negash G (2014) Treatment of skin disease using ointment of latex of Euphorbia abyssinica medicinal plant on animal model. World Appl Sci J 32(9): 1913–1917. https://doi.org/10.5829/idosi.wasj.2014.32.09.732

Mishra K, Dash AP, Dey N (2011) Andrographolide: A novel antimalarial diterpene lactone compound from Andrographis paniculata and its interaction with curcumin and artesunate. J Trop Med 2011: 579518. http://dx.doi.org/10.1155/2011/579518

Mishra SK, Sangwan NS, Sangwan RS (2007) Andrographis paniculata (Kalmegh): A Review. Pharmacogn Rev 1(2): 283–298.

Siti Najila MJ, Rain AN, Kamel AGM., Zahir SIS, Khozirah S, Hakim SL, Zakiah I, Azizol AK (2002) The screening of extracts from Goniothalamus scortechinii, Aralidium pinnatifidum and Andrographis paniculata for anti-malarial activity using the lactate dehydrogenase assay. J Ethnopharmacol 82(2–3): 239–242. https://doi.org/10.1016/s0378-8741(02)00183-6

OECD (2022) Test No. 425: Acute oral toxicity: up and down procedure, OECD guidelines for the testing of chemicals, Section 4. OECD Publishing, Paris. https://doi.org/10.1787/9789264071049-en

OECD (2008) Repeated Dose 28-day Oral Toxicity Study in Rodents, OECD guidelines for the testing of chemicals, Section 4. OECD Publishing, Paris. https://doi.org/10.1787/9789264070684-en

Prakoso NM, Zakiyah ZN, Liyanita A, Rubiyanti D, Fitriastuti D, Ramadani AP, Kamari A, Mow SK (2019) Antimalarial activity of Andrographis paniculata Ness‘s n-hexane extract and its major compounds. Open Chem 17: 788–797. http://dx.doi.org/10.1515/chem-2019-0086

Prasetyo B, Indriani ED, Viandika N, Ilmi H, Tumewu L, Widyawaruyanti A (2021) Activities of Andrographis paniculata (AS201-01) tablet on COX-2 and prostaglandin expression of placental of Plasmodium berghei infected mice. Iran J Parasitol 16(1): 43–51. https://doi.org/10.18502/ijpa.v16i1.5510

Prasetyo B, Ratih DN, Yustinasari, Ilmi H, Tumewu L, Widyawaruyanti A (2018) Treated Plasmodium berghei infected pregnant mice by Andrographis paniculata tablet (AS201-01) decreasing the TLR-4 expression and apoptosis index of placental tissue. J Appl Pharm Sci 8(4): 105–108. https://dx.doi.org/10.7324/JAPS.2018.8415

Rachmat AWJ, Viandika N, Ilmi H, Tumewu L, Prasetyo B (2018) Effect of Andrographis paniculata tablet (AS201-01) on transforming growth factor beta (TGF-β) expression and parasite inhibition in mice placenta infected with Plasmodium berghei. Bali Med J 7(1): 210–214. http://dx.doi.org/10.15562/bmj.v7i1.785

Rahman NNA, Furuta T, Kojima S, Takane K, Ali Mohd M (1999) Antimalarial activity of extracts of Malaysian medicinal plants. J Ethnopharmacol 64(3): 249–254. https://doi.org/10.1016/s0378-8741(98)00135-4

Sahota PS, Popp JA, Chirukandath G, Hardisty JF (2018) Toxicologic pathology, nonclinical safety assessment, second edition. Boca Raton : CRC Press. https://doi.org/10.1201/9780429504624

Santos SR, Rangel ET, Lima JCS, Silva RM, Lopes L, Noldin VF, Filho VC, Monache FD, and Martins DTO (2009) Toxicological and phytochemical studies of Aspidosperma subincanum Mart. stem bark (Guatambu). Pharmazie 64(12): 836–839. https://doi.org/10.1691/ph.2009.9639

Waako PJ, Gumede B, Smith P, Folb PI (2005) The in vitro and in vivo antimalarial activity of Cardiospermum halicacabum L. and Momordica foetida Schumch. Et Thonn. J Ethnopharmacol 99(1): 137–143. https://doi.org/10.1016/j.jep.2005.02.017

WHO (2021) World Malaria Report 2021. Available from: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2021

Widyawaruyanti A, Jonosewojo A, Ilmi H, Tumewu L, Imandiri A, Widiastuti E, Dachliyati L, Budiman MF, Setyawan D, Hafid AF, Tantular IS (2021) Safety evaluation of an antimalarial herbal product from Andrographis paniculata (AS201-01) in healthy volunteers. J Basic Clin Physiol Pharmacol 000010151520200381. https://doi.org/10.1515/jbcpp-2020-0381

Widyawaruyanti A, Rachmat J, Viandika N, Ilmi H, Tumewu L, Prasetyo B (2018) Effect of Andrographis paniculata tablet (AS201-01) on transforming growth factor beta (TGF-β) expression and parasite inhibition in mice placenta infected with Plasmodium berghei. Bali Med J 7(1):  210–214. https://doi.org/10.15562/bmj.v7i1.785

Zeleke G, Kebebe D, Mulisa E, Gashe F (2017) In vivo antimalarial activity of the solvent fractions of fruit rind and root of Carica papaya Linn (Caricaceae) against Plasmodium berghei in mice. J Parasitol Res 2017: 3121050. https://doi.org/10.1155/2017/3121050

© 2023 Journal of Pharmacy & Pharmacognosy Research

Bioactive compounds of Indonesian plants to inhibit Naegleria fowleri

J. Pharm. Pharmacogn. Res., vol. 11, no. 5, pp. 841-862, Sep-Oct 2023.

DOI: https://doi.org/10.56499/jppres23.1693_11.5.841

Original Article

In silico targeting CYP51 of Naegleria fowleri using bioactive compounds from Indonesian plants

[In silico dirigido a CYP51 de Naegleria fowleri utilizando compuestos bioactivos de plantas de Indonesia]

Nelson Daniel, Fisranda Ferdinand, Parikesit Arli Aditya*

Department of Bioinformatics, School of Life Sciences, Indonesia International Institute for Life-Sciences, Jl. Pulomas Barat Kav. 88, Jakarta, Indonesia.

*E-mail: arli.parikesit@i3l.ac.id

Abstract

Context: Given the elusive nature of Primary Amoebic Meningoencephalitis (PAM), caused by Naegleria fowleri, early detection is vital, yet challenging due to limited clinical indicators. This research leverages Indonesia’s rich biodiversity to explore novel sources of traditional medicine.

Aims: To evaluate the potential compounds from Indonesian plants that possess antiamoebic and antifungal properties for inhibiting the N. fowleri CYP51 protein, crucial for cell integrity.

Methods: Initially, 92 compounds were screened, and six were shortlisted following ADMETox evaluation. Subsequent steps encompassed QSAR analysis, molecular docking, and molecular dynamics simulations.

Results: The QSAR analysis verified the activity potential of these six compounds, progressing them to molecular docking analysis. Among these, curcumenol from Curcuma longa emerged as a promising contender, displaying the lowest binding affinity at -9.2 kcal/mol, indicative of superior binding compared to other ligands. Molecular dynamics simulations underscored the stability of all compounds, with root mean square fluctuation (RMSF) values within 1-3 Å.

Conclusions: Consequently, employing a comprehensive approach spanning ADMETox, QSAR, molecular docking, and dynamics simulations, curcumenol emerged as the prime candidate for inhibiting the N. fowleri CYP51 protein, suggesting its potential as a PAM therapeutic agent.

Keywords: bioactive compounds; CYP51; molecular docking; molecular dynamics; molecular simulation; Naegleria fowleri.

jppres_pdf_free

Resumen

Contexto: Dada la naturaleza elusiva de la meningoencefalitis amebiana primaria (MAP), causada por Naegleria fowleri, la detección precoz es vital, aunque difícil debido a los limitados indicadores clínicos. Esta investigación aprovecha la rica biodiversidad de Indonesia para explorar nuevas fuentes de medicina tradicional.

Objetivos: Evaluar los posibles compuestos de plantas indonesias que poseen propiedades antiamebianas y antifúngicas para inhibir la proteína CYP51 de N. fowleri, crucial para la integridad celular.

Métodos: Inicialmente, se examinaron 92 compuestos y se preseleccionaron seis tras la evaluación ADMETox. Los pasos siguientes incluyeron análisis QSAR, acoplamiento molecular y simulaciones de dinámica molecular.

Resultados: El análisis QSAR verificó el potencial de actividad de estos seis compuestos, que pasaron al análisis de acoplamiento molecular. Entre ellos, el curcumenol de Curcuma longa resultó ser un candidato prometedor, mostrando la menor afinidad de unión con -9,2 kcal/mol, lo que indica una unión superior a la de otros ligandos. Las simulaciones de dinámica molecular subrayaron la estabilidad de todos los compuestos, con valores de fluctuación cuadrática media (RMSF) dentro de 1-3 Å.

Conclusiones: En consecuencia, empleando un enfoque exhaustivo que abarca ADMETox, QSAR, acoplamiento molecular y simulaciones dinámicas, el curcumenol surgió como el principal candidato para inhibir la proteína CYP51 de N. fowleri, lo que sugiere su potencial como un agente terapéutico para la MAP.

Palabras Clave: acoplamiento molecular; compuestos bioactivos; CYP51; dinámica molecular; Naegleria fowleri; simulación molecular.

jppres_pdf_free
Citation Format: Nelson D, Fisranda F, Parikesit AA (2023) In silico targeting CYP51 of Naegleria fowleri using bioactive compounds from Indonesian plants. J Pharm Pharmacogn Res 11(5): 841–862. https://doi.org/10.56499/jppres23.1693_11.5.841
References

Agnihotri VK, ElSohly HN, Khan SI, Jacob MR, Joshi VC, Smillie T, Khan IA, Walker LA (2008) Constituents of Nelumbo nucifera leaves and their antimalarial and antifungal activity. Phytochem Lett 1(2): 89–93. https://doi.org/10.1016/j.phytol.2008.03.003

Alencar WLM, da Silva Arouche T, Neto AFG, de Castro Ramalho T, de Carvalho Júnior R N, de Jesus Chaves Neto AM (2022) Interactions of Co, Cu, and non-metal phthalocyanines with external structures of SARS-CoV-2 using docking and molecular dynamics. Sci Rep 12: 3316. https://doi.org/10.1038/s41598-022-07396-w

Arthur DE, Uzairu A (2019) Molecular docking studies on the interaction of NCI anticancer analogues with human phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit. J King Saud Univ Sci 31(4): 1151–1166. https://doi.org/10.1016/j.jksus.2019.01.011

Bharti N, Mohapatra PP, Singh S (2018) Plant-based antiamoebic natural products: Literature review and recent developments. Frontiers in Natural Product Chemistry Vol. 4, pp. 40. https://doi.org/10.2174/9781681087252118040003

BIOVIA (2022) Dassault Systèmes, Discovery Studio, v21.1.0.20298, San Diego: Dassault Systèmes.

Bornot A, Etchebest C, de Brevern AG (2011) Predicting protein flexibility through the prediction of local structures. Proteins 79(3): 839–852. https://doi.org/10.1002/prot.22922

CDC (2022). Illness & Symptoms. Naegleria fowleri. CDC. https://www.cdc.gov/parasites/naegleria/illness.html#:%7E:text=Primary%20amebic%20meningoencephalitis%20(PAM)%20is,from%201962%20to%202021%204 [Consulted October 1, 2022].

Chahal R, Nanda A, Akkol EK, Sobarzo-Sánchez E, Arya A, Kaushik D, Dutt R, Bhardwaj R, Rahman, MH, Mittal V (2021) Ageratum conyzoides L. and its secondary metabolites in the management of different fungal pathogens. Molecules 26(10): 2933. https://doi.org/10.3390/molecules26102933

Chen C, Long L, Zhang F, Chen Q, Chen C, Yu X, Liu Q, Bao J, Long Z (2018a) Antifungal activity, main active components and mechanism of Curcuma longa extract against Fusarium graminearum. PloS One 13(3): e0194284. https://doi.org/10.1371/journal.pone.0194284

Chen M, Ruan W, Zhang L, Hu B, Yang X (2019) Primary amebic meningoencephalitis: A case report. Korean J Parasitol 57(3): 291-294. https://doi.org/10.3347/kjp.2019.57.3.291

Chen T, Li M, Liu J (2018b) π–π Stacking interaction: A nondestructive and facile means in material engineering for bioapplications. Cryst Growth Des 18(5): 2765–2783. https://doi.org/10.1021/acs.cgd.7b01503

Colon BL, Rice CA, Guy RK, Kyle DE (2018) Phenotypic screens reveal posaconazole as a rapidly acting amebicidal combination partner for treatment of primary amoebic meningoencephalitis. J Infect Dis 219(7): 1095–1103. https://doi.org/10.1093/infdis/jiy622

Daina A, Michielin O, Zoete V (2017) SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7: 42717. https://doi.org/10.1038/srep42717

Daina A, Zoete V (2016) A BOILED-Egg To predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem 11(11): 1117–1121. https://doi.org/10.1002/cmdc.201600182

Dallakyan S, Olson AJ (2014) Small-molecule library screening by docking with PyRx. Methods Mol Biol 1263: 243–250. https://doi.org/10.1007/978-1-4939-2269-7_19

De Toledo LG, Ramos MA, Spósito L, Castilho EM, Pavan FR, Lopes ÉdeO, Zocolo GJ, Silva FA, Soares TH, Dos Santos AG, Bauab TM, De Almeida MT (2016) Essential oil of Cymbopogon nardus (L.) Rendle: A strategy to combat fungal infections caused by Candida species. Int J Mol Sci 17(8): 1252. https://doi.org/10.3390/ijms17081252

Debnath A, Calvet CM, Jennings G, Zhou W, Aksenov A, Luth MR, Abagyan R, Nes WD, McKerrow JH, Podust LM (2017) CYP51 is an essential drug target for the treatment of primary amoebic meningoencephalitis (PAM). PLoS Negl Trop Dis 11(12): e0006104. https://doi.org/10.1371/journal.pntd.0006104

Farah FH, Kamaruzaman S, Dzolkhifli O, Mawardi R (2013) Chemical composition and screening for antifungal activity of Allamanda spp. (Apocynaceae) crude extracts against Colletotrichum gloeosporioides, causal agent of anthracnose in papaya. Aust J Basic Appl Sci 7(1): 88-96.

Filimonov DA, Lagunin AA, Gloriozova TA, Rudik AV, Druzhilovskii DS, Pogodin PV, Poroikov VV (2014) Prediction of the biological activity spectra of organic compounds using the PASS online web resource. Chem Heterocycl Comp 50(3): 444-457. https://doi.org/10.1007/s10593-014-1496-1

Fitriani A, Hamdiyati Y, Engriyani RER (2012) Aktivitas antifungi ekstrak etanol daun salam (Syzygium polyanthum (Wight) Walp.) terhadap pertumbuhan jamur Candida albicans secara in vitro. Majalah Ilmiah Biologi BIOSFERA 29(2): 71-79. https://doi.org/10.20884/1.mib.2012.29.2.238

Gharpure R, Bliton J, Goodman A, Ali IKM, Yoder J, Cope JR (2021) Epidemiology and clinical characteristics of primary amebic meningoencephalitis caused by Naegleria fowleri: A global review. Clin Infect Dis 73(1): e19–e27. https://doi.org/10.1093/cid/ciaa520

Ghosh S, Rangan L (2013) Alpinia: the gold mine of future therapeutics. 3 Biotech 3(3): 173–185. https://doi.org/10.1007/s13205-012-0089-x

Giese M, Albrecht M (2020) Alkyl‐Alkyl interactions in the periphery of supramolecular entities: From the evaluation of weak forces to applications. ChemPlusChem 85(4): 715–724. https://doi.org/10.1002/cplu.202000077

Grace E, Asbill S, Virga K (2015) Naegleria fowleri: Pathogenesis, diagnosis, and treatment options. Antimicrob Agents Chemother 59(11): 6677–6681. https://doi.org/10.1128/AAC.01293-15

Guex N, Peitsch MC (1997) Swiss-model and the Swiss-PDB viewer: An environment for comparative protein modeling. Electrophoresis 18(15): 2714–2723. https://doi.org/10.1002/elps.1150181505

Hollingsworth SA, Dror RO (2018) Molecular dynamics simulation for all. Neuron 99(6): 1129-1143. https://doi.org/10.1016/j.neuron.2018.08.011

Irianti MI, Elya B, Rahmasari R, Puspitasari N, Maharani FH, Raekiansyah M (2021) Averrhoa carambola leaf from Depok, West Java, Indonesia: Phytochemistry characterization and prospective anti-candidiasis activity. J Appl Pharm Sci 12(1): 199-207. https://doi.org/10.7324/japs.2021.120120

Jendri M, Lucas WM, Arman H, Dana B, Cengiz K (2022) Endophytic bacteria and fungi from Indonesian medicinal plants with antibacterial, pathogenic antifungal and extracellular enzymes activities: A review. Int J Sci Technol Manag 3(1): 245–255. https://doi.org/10.46729/ijstm.v3i1.428

Kaur K, Kaushal S, Rani R (2019) Chemical composition, antioxidant and antifungal potential of clove (Syzygium aromaticum) essential oil, its major compound and its derivatives. J Essent Oil Bearing Plants 22(5): 1195–1217. https://doi.org/10.1080/0972060x.2019.1688689

Kumar, N, Sood D, Tomar R, Chandra R. (2019) Antimicrobial peptide designing and optimization employing large-scale flexibility analysis of protein-peptide fragments. ACS Omega 4(25): 21370–21380. https://doi.org/10.1021/acsomega.9b03035

Kurcinski M, Oleniecki T, Ciemny M, Kuriata A, Kolinski A, Kmiecik S (2018) CABS-flex standalone: A simulation environment for fast modeling of protein flexibility. Bioinformatics 35(4): 694–695. https://doi.org/10.1093/bioinformatics/bty685

Kusuma IW, Arung ET, Rosamah E, Purwatiningsih S, Kuspradini H, Syafrizal AJ, Kim YU, Shimizu K (2010) Antidermatophyte and antimelanogenesis compound from Eleutherine americana grown in Indonesia. J Nat Med 64(2): 223–226. https://doi.org/10.1007/s11418-010-0396-7

Lagunin A, Stepanchikova A, Filimonov D, Poroikov V (2000) PASS: Prediction of activity spectra for biologically active substances. Bioinformatics 16(8): 747–748. https://doi.org/10.1093/bioinformatics/16.8.747

Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) PROCHECK: A program to check the stereochemical quality of protein structures. J Appl Crystallogr 26(2): 283–291. https://doi.org/10.1107/S0021889892009944

Mangas-Sanjuan V, González-Alvarez M, Gonzalez-Alvarez I, Bermejo M (2010) Drug penetration across the blood–brain barrier: an overview. Therc Deliv 1(4): 535–562. https://doi.org/10.4155/tde.10.37

Muchtaromah B, Ahmad M, Hasan MN, Wahyudi D (2017) Antioxidant and antifungal activity of Jeringau (Acorus Calamus L.) extract in some organic solvents in vitro. El-Hayah 6(3): 70–78. https://doi.org/10.18860/elha.v6i3.5334

Nayaka NMDMW, Sasadara MMV, Sanjaya DA, Yuda PESK, Dewi NLKAA, Cahyaningsih E, Hartati R (2021) Piper betle (L): Recent review of antibacterial and antifungal properties, safety profiles, and commercial applications. Molecules 26(8): 2321. https://doi.org/10.3390/molecules26082321

O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR (2011) Open babel: An open chemical toolbox. J Cheminform 3: 33. https://doi.org/10.1186/1758-2946-3-33

Ottaviani G, Gosling DJ, Patissier C, Rodde S, Zhou L, Faller B (2010) What is modulating solubility in simulated intestinal fluids?. Eur J Pharm Sci 41(3-4): 452-457. https://doi.org/10.1016/j.ejps.2010.07.012

Parikesit AA, Nurdiansyah R (2021) Natural products repurposing of the H5N1-based lead compounds for the most fit inhibitors against 3C-like protease of SARS-CoV-2. J Pharm Pharmacogn Res 9(5): 730–745. https://doi.org/10.56499/jppres21.1080_9.5.730

Podust LM, Jennings G, Calvet-Alvarez C, Debnath A (2017) RCSB PDB – 5TL8: Naegleria fowleri CYP51-posaconazole complex. https://www.rcsb.org/structure/5TL8 [Consulted October 11, 2022].

Pusat Teknologi dan Data Penginderaan Jauh. (2020). Informasi Suhu Permukaan Laut. SIPANDORA. https://sipandora.lapan.go.id/site/suhupermukaanlaut [Consulted October 1, 2022].

Renantha RR, Liga AR, Tanugroho B, Denovian LX, Budiyanto SLAZ, Parikesit AA (2022) Flavonoids as potential inhibitors of dengue virus 2 (DENV2) envelope protein. J Pharm Pharmacogn Res 10(4): 660-675. https://doi.org/10.56499/jppres22.1375_10.4.660

Rita WS, Kawuri R, Swantara IMD (2017) The essential oil contents of jeringau (Acorus calamus L.) rhizomes and their antifungal activity against Candida albicans. J Health Sci Med 1(1): 33-38. https://doi.org/10.24843/jhsm.2017.v01.i01.p09

Savjani KT, Gajjar AK, Savjani JK (2012) Drug solubility: importance and enhancement techniques. ISRN Pharm 2012: 195727. https://doi.org/10.5402/2012/195727

Shivanika C, Deepak Kumar S, Ragunathan V, Tiwari P, Sumitha A, Brindha Devi P (2020) Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease. J Biomol Struct Dyn 40(2): 585-611. https://doi.org/10.1080/07391102.2020.1815584

Schöning-Stierand K, Diedrich K, Fährrolfes R, Flachsenberg F, Meyder A, Nittinger E, Steinegger R, Rarey M (2020) ProteinsPlus: Interactive analysis of protein–ligand binding interfaces. Nucleic Acids Res 48(W1): W48-W53. https://doi.org/10.1093/nar/gkaa235

Schrodinger LLC. (2010) The PyMOL Molecular Graphics System, Version 2.5.0

Sinan KI, Zengin G, Zheleva-Dimitrova D, Gevrenova R, Picot-Allain MCN, Dall’Acqua S, Behl T, Goh BH, Ying, PTS, Mahomoodally MF (2021) Exploring the chemical profiles and biological values of two spondias species (S. dulcis and S. mombin): Valuable sources of bioactive natural products. Antioxidants 10(11): 1771. https://doi.org/10.3390/antiox10111771

Siswina T, Miranti Rustama M, Sumiarsa D, Kurnia D (2022) Phytochemical profiling of Piper crocatum and its antifungal activity as lanosterol 14 alpha demethylase CYP51 inhibitor: a review. F1000Research 11: 1115. https://doi.org/10.12688/f1000research.125645.1

Soltow SM, Brenner GM (2007) Synergistic activities of azithromycin and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis. Antimicrobiol Agents Chemother 51(1): 23–27. https://doi.org/10.1128/aac.00788-06

Sutiono DR, Aisyah S. (2017). Primary amebic meningoencephalitis (PAM). Cermin Dunia Kedokteran 44(12). http://dx.doi.org/10.55175/cdk.v44i12.687

Taravaud A, Fechtali‐Moute Z, Loiseau PM, Pomel S (2021) Drugs used for the treatment of cerebral and disseminated infections caused by free‐living amoebae. Clin Transl Sci 14(3): 791–805. https://doi.org/10.1111/cts.12955

Terças AG, Monteiro AS, Moffa EB, Dos Santos JRA, de Sousa EM, Pinto ARB, Costa PCDS, Borges ACR, Torres, LMB, Barros Filho AKD, Fernandes ES, Monteiro CA (2017) Phytochemical characterization of Terminalia catappa Linn. extracts and their antifungal activities against Candida spp. Front Microbiol 8: 595. https://doi.org/10.3389/fmicb.2017.00595

Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31(2): 455–461. https://doi.org/10.1002/jcc.21334

Vijayaraghavan K, Rajkumar J, Bukhari SN, Al-Sayed B, Seyed MA (2017) Chromolaena odorata: A neglected weed with a wide spectrum of pharmacological activities. Mol Med Rep 15(3): 1007–1016. https://doi.org/10.3892/mmr.2017.6133

Von Rintelen K, Arida E, Häuser C (2017) A review of biodiversity-related issues and challenges in Megadiverse Indonesia and other Southeast Asian countries. Res Ideas Outcomes 3: e20860. https://doi.org/10.3897/rio.3.e20860

Wang SY, Chen PF, Chang ST (2005) Antifungal activities of essential oils and their constituents from indigenous cinnamon (Cinnamomum osmophloeum) leaves against wood decay fungi. Bioresour Technol 96(7): 813–818. https://doi.org/10.1016/j.biortech.2004.07.010

Wardana FY, Sari DK, Adianti M, Permanasari AA, Tumewu L, Nozaki T, Widyawaruyanti A, Hafid AF (2018) Amoebicidal activities of Indonesian medicinal plants in Balikpapan, East Kalimantan. Proceedings of BROMO Conference (BROMO2018), p. 77-82. https://doi.org/10.5220/0008357700770082

Wishart DS (2007) Improving early drug discovery through ADME modelling. Drugs R D 8(6): 349–362. https://doi.org/10.2165/00126839-200708060-00003

Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C, Yin M, Zeng X, Wu C, Lu A, Chen X, Hou T, Cao D (2021) ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res 49(W1): W5-W14. https://doi.org/10.1093/nar/gkab255

Xu D-H, Huang Y-S, Jiang D-Q, Yuan K (2013) The essential oils chemical compositions and antimicrobial, antioxidant activities and toxicity of three Hyptis species. Pharm Biol 51(9): 1125–1130. https://doi.org/10.3109/13880209.2013.781195

Yan A, Wang Z, Cai Z (2008) Prediction of human intestinal absorption by GA feature selection and support vector machine regression. Int J Mol Sci 9(10): 1961–1976. https://doi.org/10.3390/ijms9101961

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