Category Archives: Pharmaceutical Science

System optimization and validation of roselle

J. Pharm. Pharmacogn. Res., vol. 11, no. 2, pp. 243-254, March-April 2023.

DOI: https://doi.org/10.56499/jppres22.1566_11.2.243

Original Article

System optimization and validation to improve thin-layer chromatography of roselle calyces (Hibiscus sabdariffa L.) required by the Indonesian Herbal Pharmacopoeia Edition II

[Optimización y validación del sistema para mejorar la cromatografía en capa fina de cálices de rosa mosqueta (Hibiscus sabdariffa L.) requerida por la Farmacopea Herbal Indonesia Edición II]

Bhujangga Agung Ayu Sri Kartika Dewi, Kartini Kartini*

Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Surabaya, Surabaya, Indonesia.

*E-mail: kartini@staff.ubaya.ac.id

Abstract

Context: Roselle (Hibiscus sabdariffa L.) is one of the traditional crude drugs monographed in the Indonesian Herbal Pharmacopoeia Edition II (IHP II). As per IHP II requirements, a TLC pattern should be used in its authentication. However, the TLC system described for this purpose does not produce a clear reference chromatogram, often leading to inconclusive results.

Aims: To develop and validate TLC systems of H. sabdariffa calyces for a better-quality chromatogram than those listed in the IHP II, thereby facilitating crude drugs authentication.

Methods: To optimize TLC for H. sabdariffa, sixteen systems, differing in stationary phase, mobile phase composition, and/or visualization reagent were tested. The TLC system was then validated using several parameters such as analyte stability during chromatography, analyte stability in the extract solution and on the TLC plate, stability of the derivatization result, and precision on a plate as well as intermediate precision.

Results: Two systems (I and II) were successfully designed and applied to evaluate H. sabdariffa quality. System I used Si gel 60 F254 for the stationary phase, ethyl acetate-formic acid-glacial acetic acid-water (100:11:11:2) for the mobile phase, H. sabdariffa’s ethanol extract (5%, 20 µL) for the test solution, cyanidin 3-O-glucoside (100 ppm, 4 µL) as a reference, no derivatization, and detection with visible light. System II combined Si gel 60 F254 for the stationary phase, ethyl acetate-formic acid-glacial acetic acid-toluene-water (80:11:11:20:19), H. sabdariffa’s ethanol extract (5%, 20 µL) for the test solution, chlorogenic acid (1000 ppm, 2 µL) and caffeic acid (50 ppm, 2 µL) as references, the visualizing reagent NP/PEG, and investigation under 366 nm UV light.

Conclusions: Both systems are simple but have good stability and precision, thus facilitating H. sabdariffa calyx authentication and paving the way for developing content analysis methods for H. sabdariffa markers.

Keywords: authenticity; herbal pharmacopoeia; quality evaluation; roselle; TLC pattern.

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Resumen

Contexto: La rosa mosqueta (Hibiscus sabdariffa L.) es una de las drogas crudas tradicionales monografiadas en la segunda edición de la Farmacopea Herbal Indonesia (PHI II). Según los requisitos de la PHI II, se debe utilizar un patrón de TLC para su autentificación. Sin embargo, el sistema de TLC descrito para este fin no produce un cromatograma de referencia claro, lo que a menudo conduce a resultados no concluyentes.

Objetivos: Desarrollar y validar sistemas de TLC de cálices de H. sabdariffa para obtener un cromatograma de mejor calidad que los listados en el PHI II, facilitando así la autentificación de drogas crudas.

Métodos: Para optimizar la TLC para H. sabdariffa, se probaron dieciséis sistemas, que diferían en la fase estacionaria, la composición de la fase móvil y/o el reactivo de visualización. A continuación, se validó el sistema de TLC utilizando varios parámetros, como la estabilidad del analito durante la cromatografía, la estabilidad del analito en la solución del extracto y en la placa de TLC, la estabilidad del resultado de la derivatización y la precisión en una placa, así como la precisión intermedia.

Resultados: Se diseñaron y aplicaron con éxito dos sistemas (I y II) para evaluar la calidad de H. sabdariffa. El sistema I utilizó Si gel 60 F254 como fase estacionaria, acetato de etilo-ácido fórmico-ácido acético glacial-agua (100:11:11:2) como fase móvil, extracto de etanol de H. sabdariffa (5%, 20 µL) como solución de prueba, cianidina 3-O-glucósido (100 ppm, 4 µL) como referencia, sin derivatización, y detección con luz visible. El sistema II combinó Si gel 60 F254 para la fase estacionaria, acetato de etilo-ácido fórmico-ácido acético glacial-tolueno-agua (80:11:11:20:19), extracto de etanol de H. sabdariffa (5%, 20 µL) para la solución de prueba, ácido clorogénico (1000 ppm, 2 µL) y ácido cafeico (50 ppm, 2 µL) como referencias, el reactivo de visualización NP/PEG, y la investigación bajo luz UV de 366 nm.

Conclusiones: Ambos sistemas son sencillos pero tienen buena estabilidad y precisión, facilitando así la autentificación del cáliz de H. sabdariffa y allanando el camino para desarrollar métodos de análisis de contenido para marcadores de H. sabdariffa.

Palabras Clave: autenticidad; farmacopea herbal; evaluación de la calidad; rosa mosqueta; patrón TLC.

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Citation Format: Dewi BAASK, Kartini K (2023) System optimization and validation to improve thin-layer chromatography of roselle calyces (Hibiscus sabdariffa L.) required by the Indonesian Herbal Pharmacopoeia Edition II. J Pharm Pharmacogn Res 11(2): 243–254. https://doi.org/10.56499/jppres22.1566_11.2.243
References

Ali BH, Wabel NA, Blunden G (2005) Phytochemical, pharmacological and toxicological aspects of Hibiscus sabdariffa L.: A review. Phytother Res. 19: 369–375. https://doi.org/10.1002/ptr.1628

Antonia YT, Nii AA, Nancy C, Achana N (2019) Genetic diversity, variability and characterization of the agro-morphological traits of Northern Ghana Roselle (Hibiscus sabdariffa var. altissima) accessions. Afr J Plant Sci 13: 168–184. https://doi.org/10.5897/AJPS2019.1783

Aryanti N, Nafiunisa A, Wardhani DH (2019) Conventional and ultrasound-assisted extraction of anthocyanin from red and purple roselle (Hibiscus sabdaria L.) calyces and characterisation of its anthocyanin powder. Int Food Res J 26: 529–535.

Chan SS-K, Li S-L, Lin G (2007) Pitfalls of the selection of chemical markers for the quality control of medicinal herbs. J Food Drug Anal 15: 365–371. https://doi.org/10.38212/2224-6614.2398

Chumsri P, Sirichote A, Itharat A (2008) Studies on the optimum conditions for the extraction and concentration of roselle (Hibiscus sabdariffa Linn.) extract. Songklanakarin J Sci Technol 30: 133-139.

Committee MHM (2015) Malaysian Herbal Monograph 2015: Institute for Medical Research.

EDQM (2008) European Pharmacopeia 7.0, Strasbourg: The Directorate for the Quality of Medicines of the Council of Europe (EDQM).

Hapsari BW, Setyaningsih W (2021) Methodologies in the analysis of phenolic compounds in roselle (Hibiscus sabdariffa L.): Composition, biological activity, and beneficial effects on human health. Horticulturae 7: 35. https://doi.org/10.3390/horticulturae7020035

Health IMO (2017) Farmakope Herbal Indonesia Edisi II, Jakarta: Departemen Kesehatan Republik Indonesia.

Izquierdo-Vega JA, Arteaga-Badillo DA, Sánchez-Gutiérrez M, Morales-González JA, Vargas-Mendoza N, Gómez-Aldapa CA, Castro-Rosas J, Delgado-Olivares L, Madrigal-Bujaidar E, Madrigal-Santillán E (2020) Organic acids from roselle (Hibiscus sabdariffa L.)—A brief review of its pharmacological effects. Biomedicines 8: 100. https://doi.org/10.3390/biomedicines8050100

Kartini K, Andriani YA, Priambodo W, Jayani NI, Hadiyat MA (2021) Validating and developing TLC-based fingerprinting for Curcuma longa L. J Pharm Pharmacogn Res. 9: 704–715. https://doi.org/10.56499/jppres21.1062_9.5.704

Kim Y-H, Cho ML, Kim D-B, Shin G-H, Lee J-H, Lee JS, Park S-O, Lee S-J, Shin HM, Lee O-H (2015) The antioxidant activity and their major antioxidant compounds from Acanthopanax senticosus and A. koreanum. Molecules 20: 13281–13295. https://doi.org/10.3390/molecules200713281

Lago C, Landoni M, Cassani E, Atanassiu S, Cantaluppi E, Pilu R (2014) Development and characterization of a coloured sweet corn line as a new functional food. Maydica 59: 191–200.

Orfali R, Perveen S, Aati HY, Alam P, Noman OM, Palacios J, Al-Kurbi BSS, Al-Taweel AM, Khan A, Mehmood R (2021) High-performance thin-Layer chromatography for rutin, chlorogenic acid, caffeic acid, ursolic acid, and stigmasterol analysis in Periploca aphylla extracts. Separations 8: 44. https://doi.org/10.3390/separations8040044

Pham TN, Nguyen TNP, Lam TD, Tran TH, Nguyen DC, Vo D-VN, Le XT, Do ST, Bach LG (2019) Effects of various solvent concentration, liquid-solid ratio, temperatures and time values on the extraction yield of anthocyanin from Vietnam Hibiscus sabdariffa L. (roselle). IOP Conf Ser: Mater Sci Eng 542: 012033. https://doi.org/10.1088/1757-899X/542/1/012033

Reich E, Schibli A (2007) High-performance thin-layer chromatography for the analysis of medicinal plants. Stuttgart: Thieme. https://doi.org/10.1055/b-0034-65188

Santos DT, Cavalcanti RN, Rostagno MA, Queiroga CL, Eberlin MN, Meireles MA (2013) Extraction of polyphenols and anthocyanins from the jambul (Syzygium cumini) fruit peels. Food Public Health 3: 12–20. https://doi.org/10.5923/j.fph.20130301.02

Spangenberg B, Poole CF, Weins C (2011) Quantitative thin-layer chromatography: A practical survey. Springer Berlin, Heidelberg. Pp. XV, 388. https://doi.org/10.1007/978-3-642-10729-0

Sukkhaeng S, Promdang S, Doung-Ngern U (2018) Fruit characters and physico-chemical properties of roselle (Hibiscus sabdariffa L.) in Thailand—A screening of 13 new genotypes. J Appl Res Med Aromat Plants 11: 47–53. https://doi.org/10.1016/j.jarmap.2018.10.001

Torres-Morán MI, Escoto-Delgadillo M, Ron-Parra J, Parra-Tovar G, Mena-Munguía S, Rodríguez-García A, Rodríguez-Sahagún A (2011) Relationships among twelve genotypes of roselle (Hibiscus sabdariffa L.) cultivated in western Mexico. Ind Crops Prod 34: 1079–1083. https://doi.org/10.1016/j.indcrop.2011.03.0205

© 2023 Journal of Pharmacy & Pharmacognosy Research

Chitosan-alginate scaffold with Zingiber officinale for neural tissue engineering

J. Pharm. Pharmacogn. Res., vol. 11, no. 2, pp. 229-242, March-April 2023.

DOI: https://doi.org/10.56499/jppres22.1505_11.2.229

Original Article

Chitosanalginate porous scaffold incorporated with hydroalcoholic Zingiber officinale Roscoe extract for neural tissue engineering

[Estructura porosa de quitosano-alginato incorporada con extracto hidroalcohólico de Zingiber officinale Roscoe para la ingeniería del tejido neural]

Hassan Sohrabian Kafraj1, Maryam Alipour2, Abdolhosein Shiravi1, Vida Hojati1, Mojtaba Khaksarian2*

1Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.

2Razi Herbal Medicines Research Center and Department of Physiology, Lorestan University of Medical Sciences, Khorramabad, Iran.

*E-mail: mojkhaksar@lums.ac.ir, mojkhaksar@yahoo.com

Abstract

Context: Preparing a suitable substrate for the culture of neural stem cells and their proliferation in neural tissue engineering is of paramount importance.

Aims: To evaluate the effect of the hydroalcoholic Zingiber officinale extract incorporated in the chitosan-alginate scaffold (Chi-Alg-Zo) on nerve tissue.

Methods: The porous scaffolds developed in the present study were investigated in terms of their surface properties, chemical interaction, crystallinity, thermal stability, porosity percentage, pore sizes, degradability, and water absorption properties. To this end, the following tests were performed: Field emission scanning electron microscope (FE-SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), thermal gravimetric analysis (TGA), porosity based on liquid replacement, Image-J analysis, and water degradation and absorption test. Mouse neural stem/progenitor cells (NS/PCs) were harvested from the embryonic mouse brain. NSCs were seeded on scaffolds incorporated with hydroalcoholic Z. officinale extract. The MTT assay was done for the survival and the proliferation of neural stem/progenitor cells (NS/PCs) on scaffolds.

Results: Results indicated the good capacity of Chi-Alg-Zo for proliferation and differentiation into glial (astrocytes and oligodendrocytes) lineages. A suitable surface, which was provided for cellular interaction, led to the advancement of cell survival, connectivity, proliferation, and separation of NSCs.

Conclusions: The present study evaluated the separation of stem cells on the scaffold, finding that the expression of the glial fibrillary acidic protein (GFAP) and Oligo4 markers was higher in Chi-Alg scaffolds containing hydroalcoholic Z. officinale extract. Chi-Alg-Zo scaffolds could be suitable candidates for neural tissue engineering.

Keywords: neural tissue engineering; neural stem/progenitor cells; chitosan-alginate scaffold; ginger extract.

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Resumen

Contexto: La preparación de un sustrato adecuado para el cultivo de las células madre neurales y su proliferación en la ingeniería del tejido neural es de suma importancia.

Objetivos: Evaluar el efecto del extracto hidroalcohólico de Zingiber officinale incorporado al andamio de quitosano-alginato (Chi-Alg-Zo) en el tejido nervioso.

Métodos: Los andamios porosos desarrollados en el presente estudio fueron investigados en cuanto a sus propiedades superficiales, interacción química, cristalinidad, estabilidad térmica, porcentaje de porosidad, tamaño de los poros, degradabilidad y propiedades de absorción de agua. Para ello, se realizaron las siguientes pruebas: Microscopio electrónico de barrido de emisión de campo (FE-SEM), espectroscopia infrarroja por transformada de Fourier (FTIR), difracción de polvo de rayos X (XRD), análisis termo gravimétrico (TGA), porosidad basada en la sustitución de líquidos, análisis Image-J, y ensayo de degradación y absorción de agua. Las células madre/progenitoras neurales de ratón (NSC/PCs) fueron cosechadas del cerebro embrionario de ratón. Las NSC se sembraron en andamios incorporados con extracto hidroalcohólico de Z. officinale. Se realizó el ensayo MTT para la supervivencia y la proliferación de las células madre/progenitoras neurales (NS/PCs) en los andamios.

Resultados: Los resultados indicaron la buena capacidad de Chi-Alg-Zo para la proliferación y diferenciación en linajes gliales (astrocitos y oligodendrocitos). Una superficie adecuada, que se proporcionó para la interacción celular condujo al avance de la supervivencia celular, la conectividad, la proliferación y la separación de las NSC.

Conclusiones: El presente estudio evaluó la separación de las células madre en el andamio, encontrando que la expresión de los marcadores de proteína ácida fibrilar glial (GFAP) y Oligo4 era mayor en los andamios Chi-Alg que contenían extracto hidroalcohólico de Z. officinale. Los andamios Chi-Alg-Zo podrían ser candidatos adecuados para la ingeniería del tejido neural.

Palabras Clave: ingeniería de tejidos neurales; células madre/progenitoras neurales; andamio de quitosano-alginato; extracto de jengibre.

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Citation Format: Sohrabian Kafraj H, Alipour M, Shiravi A, Hojati V, Khaksarian M (2022) Chitosan-alginate porous scaffold incorporated with hydroalcoholic Zingiber officinale Roscoe extract for neural tissue engineering. J Pharm Pharmacogn Res 11(2): 229–242. https://doi.org/10.56499/jppres22.1505_11.2.229
References

Akbari A, Nasiri K, Heydari M, Mosavat SH, Iraji A (2017) The protective effect of hydroalcoholic extract of Zingiber officinale Roscoe (Ginger) on ethanol-induced reproductive toxicity in male rats. J Evid Based Complement Alternat Med 22(4): 609–617. https://doi.org/10.1177/2156587216687696

Aligholi H, Rezayat SM, Azari H, Mehr SE, Akbari M, Mousavi SMM, Gorji A (2016) Preparing neural stem/progenitor cells in PuraMatrix hydrogel for transplantation after brain injury in rats: A comparative methodological study. Brain Res 1642: 197–208. https://doi.org/10.1016/j.brainres.2016.03.043

Alipour M, Bigdelie M, Bigdeli R, Aligholi H, Rasoulian B, Khaksarian M (2020) Sustained release of silibinin‐loaded chitosan nanoparticle induced apoptosis in glioma cells. J Biomed Materials Res Part A 108(3): 458–469. https://doi.org/10.1002/jbm.a.36827

Asnani V, Verma RJ (2007) Antioxidative effect of rhizome of Zingiber officinale on paraben induced lipid peroxidation: An in vitro study. Acta Pol Pharm 64(1): 35-37.

Becker TA, Kipke DR, Brandon T (2001) Calcium alginate gel: A biocompatible and mechanically stable polymer for endovascular embolization. J Biomed Mat Res 54(1): 76–86.‏ https://doi.org/10.1002/1097-4636(200101)54:1<76::aid-jbm9>3.0.co;2-v

Binulal NS, Deepthy M, Selvamurugan N, Shalumon KT, Suja S, Mony U, Nair SV (2010) Role of nanofibrous poly (caprolactone) scaffolds in human mesenchymal stem cell attachment and spreading for in vitro bone tissue engineering—response to osteogenic regulators. Tissue Eng Part A 16(2): 393–404. https://doi.org/10.1089/ten.TEA.2009.0242

Duarte ARC, Mano JF, Reis RL (2009) Preparation of chitosan scaffolds loaded with dexamethasone for tissue engineering applications using supercritical fluid technology. Eur Polymer J 45(1): 141–148. https://doi.org/10.1016/j.eurpolymj.2008.10.004

El-Kady AM, Saad EA, Abd El-Hady BM, Farag MM (2010) Synthesis of silicate glass/poly (l-lactide) composite scaffolds by freeze-extraction technique: characterization and in vitro bioactivity evaluation. Ceramics Int 36(3): 995–1009. https://doi.org/10.1016/j.ceramint.2009.11.012

Freier T, Montenegro R, Koh HS, Shoichet MS (2005) Chitin-based tubes for tissue engineering in the nervous system. Biomaterials 26(22): 4624–4632. https://doi.org/10.1016/j.biomaterials.2004.11.040

Ghasemi‐Mobarakeh L, Prabhakaran MP, Morshed M, Nasr‐Esfahani MH, Baharvand H, Kiani S, Ramakrishna S (2011) Application of conductive polymers, scaffolds and electrical stimulation for nerve tissue engineering. J Tissue Eng Regener Med 5(4): 17–35. https://doi.org/10.1002/term.383

Gu X, Ding F, Williams DF (2014) Neural tissue engineering options for peripheral nerveregeneration. Biomaterials 35(24): 6143–6156. https://doi.org/10.1016/j.biomaterials.2014.04.064

Habib SHM, Makpol S, Hamid NAA, Das S, Ngah WZ W, Yusof YAM (2008) Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats. Clinics 63(6): 807–813.‏ https://doi.org/10.1590/S1807-59322008000600017

Han YA, Song CW, Koh WS, Yon GH, Kim YS, Ryu SY, Lee, KH (2013) Anti‐inflammatory effects of the Zingiber officinale Roscoe constituent 12‐dehydrogingerdione in lipopolysaccharide‐stimulated RAW264.7 cells. Phytother Res 27(8): 1200–1205. https://doi.org/10.1002/ptr.4847

Hassanzadeh Khanmiri H, Amer Mohammad A, Yousif RS, Jasim SA, Kzar HH, Lafta MH, Turki Jalil A, Romero Parra RM, Darvishi M (2022) SARS-CoV2 neuroinvasive potential in respiratory failure in COVID-19 patients. Casp J Environ Sci. https://doi.org/10.22124/cjes.2022.5964

Khan W, Ashfaq UA, Aslam S, Saif S, Aslam T, Tusleem K, Maryam A, Qamar MT (2017) Anticancer screening of medicinal plant phytochemicals against cyclin-dependent kinase-2 (CDK2): An in-silico approach. Adv Life Sci 4(4): 113–120.

Leena RS, Vairamani M, Selvamurugan N (2017) Alginate/Gelatin scaffolds incorporated with silibinin-loaded chitosan nanoparticles for bone formation in vitro. Colloids and Surf B: Biointerfaces 158: 308–318. https://doi.org/10.1016/j.colsurfb.2017.06.048

Li Z, Leung M, Hopper R, Ellenbogen R, Zhang M (2010) Feeder-free self-renewal of human embryonic stem cells in 3D porous natural polymer scaffolds. Biomaterials 31(3): 404–412.‏ https://doi.org/10.1016/j.biomaterials.2009.09.070

Levene HB, Lhommeau CM, Kohn JB (2000) Porous polymer scaffolds for tissue engineering, Google Patents, US6103255A.

Mani MP, Jaganathan SK, Ismail AF (2019) Appraisal of electrospun textile scaffold comprising polyurethane decorated with ginger nanofibers for wound healing applications. J Indust Text 49(5): 648–662. https://doi.org/10.1177/1528083718795911

Panawes S, Ekabutr P, Niamlang P, Pavasant P, Chuysinuan P, Supaphol P (2017) Antimicrobial mangosteen extract infused alginate-coated gauze wound dressing. J Drug Delivery Sci Technol 41: 182–190. ‏https://doi.org/10.1016/j.jddst.2017.06.021

Pereira R, Mendes A, Bártolo P (2013) Alginate/Aloe vera hydrogel films for biomedical applications. Procedia CIRP 5: 210–215.‏‏ https://doi.org/10.1016/j.procir.2013.01.042

Radhakrishnan EK, Bava SV, Narayanan SS, Nath LR, Thulasidasan AK T, Soniya EV, Anto RJ (2014) Gingerol induces caspase-dependent apoptosis and prevents PMA-induced proliferation in colon cancer cells by inhibiting MAPK/AP-1 signaling. PloS One 9(8): 104401. https://doi.org/10.1371/journal.pone.0104401

Schmidt CE, Leach JB (2003) Neural tissue engineering: Strategies for repair and regeneration. Ann Rev Biomed Engin 5(1): 293–347.‏ https://doi.org/10.1146/annurev.bioeng.5.011303.120731

Sowjanya JA, Singh J, Mohita T, Sarvanan S, Moorthi A, Srinivasan N, Selvamurugan N (2013) Biocomposite scaffolds containing chitosan/alginate/nano-silica for bone tissue engineering. Colloids Surf B: Biointerfaces 109: 294–300. https://doi.org/10.1016/j.colsurfb.2013.04.006

Subramanian A, Krishnan UM, Sethuraman S (2009) Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration. J Biomed Sci 16: 108. https://doi.org/10.1186/1423-0127-16-108

‏Venkatesan J, Lee JY, Kang DS, Anil S, Kim SK, Shim MS, Kim DG (2017) Antimicrobial and anticancer activities of porous chitosan-alginate biosynthesized silver nanoparticles. Int J Biolog Macromol 98: 515–525. https://doi.org/10.1016/j.ijbiomac.2017.01.120

Venkatesan J, Bhatnagar I, Kim SK (2014) Chitosan-alginate biocomposite containing fucoidan for bone tissue engineering. Mar Drugs 12(1): 300–316. https://doi.org/10.3390/md12010300

Waggas AM (2009) Neuroprotective evaluation of extract of ginger (Zingiber officinale) root in monosodium glutamate-induced toxicity in different brain areas male albino rats. Pak J Biolog Sci 12(3): 201–221. https://doi.org/10.3923/pjbs.2009.201.212

Wang S, Guan S, Zhu Z, Li W, Liu T, Ma X (2017) Hyaluronic acid doped-poly (3, 4-ethylenedioxythiophene)/chitosan/gelatin (PEDOT-HA/Cs/Gel) porous conductive scaffold for nerve regeneration. Mater Sci Eng C 71: 308–316. https://doi.org/10.1016/j.msec.2016.10.029

Yuan NY, Tsai RY, Ho MH, Wang DM, Lai JY, Hsieh HJ (2008) Fabrication and characterization of chondroitin sulfate-modified chitosan membranes for biomedical applications. Desalination 234(1-3): 166–174. https://doi.org/10.1016/j.desal.2007.09.083

Zheng X, Shen G, Yang X, Liu W (2007) Most C6 cells are cancer stem cells: evidence from clonal and population analyses. Cancer Res 67(8): 3691–3697. https://doi.org/10.1158/0008-5472.CAN-06-3912

© 2023 Journal of Pharmacy & Pharmacognosy Research

Ilex paraguariensis and eggshell membrane vs. aging

J. Pharm. Pharmacogn. Res., vol. 11, no. 2, pp. 216-228, March-April 2023.

DOI: https://doi.org/10.56499/jppres22.1509_11.2.216

Original Article

Oral supplementation of Ilex paraguariensis extract and eggshell membrane exhibit beneficial effects on the skin of mature male rats

[La suplementación oral de extracto de Ilex paraguariensis y membrana de cáscara de huevo muestran efectos beneficiosos sobre la piel de ratas macho maduras]

Maria R. Ramirez1,2*, Ignacio Rintoul2,3, Manuel Leiva1, José S. Molli2,3, Juan C. Yori2,3

1Instituto Universitario de Ciencias de la Salud, Fundación Barceló, Centeno 710, Santo Tome CP 3340, Argentina.

2Consejo Nacional de Investigaciones Científicas Técnicas (CONICET), Buenos Aires C1033AAJ, Argentina.

3Facultad deIngeniería Química. Universidad Nacional del Litoral, Colectora Ruta Nac, 168, Santa Fe CP 3000, Argentina.

*E-mail: mr.ramirez@conicet.gov.ar

Abstract

Context: Ilex paraguariensis (IP), a South American plant mostly consumed as an infusion, contains several phytocompounds with demonstrated positive effects on skin health and photoprotective properties. Eggshell membrane (ESM), a by-product of the poultry industry, also presents photoprotective properties. Both IP and ESM contain compounds that absorb ultraviolet radiation (UVR) and stop the mechanisms by which UVR damages the skin. The synergistic effects of these natural products on the reparation of skin structure and dermal collagen production deserves to be investigated.

Aims: To determine to what extent the oral supplementation of IP and ESM, administrated individually or in combination, promotes beneficial effects on the skin of mature Wistar rats.

Methods: The chemical composition of IP and ESM and the spectrophotometric solar protection factor (SPF) of the IP extract were characterized. In vitro, antioxidant and anti-inflammatory effects were assessed using erythrocytes. In vivo investigation consisted of macro and microscopic image analysis and diagnosis of the skin of the dorsal region of rats.

Results: The IP extract showed low SPF capacity combined with a protective effect against AAPH-induced erythrocyte haemolysis. IP extract inhibited erythrocyte haemolysis induced by both hypotonic solution and heat. The antioxidant and anti-inflammatory activity of the IP could be explained in terms of its membrane-stabilizing properties. Histologic analysis showed an increase in the collagen content of the skin of supplemented rats. A clear synergistic increase in collagen levels resulted when IP and ESM were administered together.

Conclusions: IP and ESM are beneficial for skin health, present synergistic effects, and could be used as ingredients in oral cosmetics.

Keywords: chemopreventive capacity; membrane-stabilizing property; skin structure.

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Resumen

Contexto: El Ilex paraguariensis (IP), planta sudamericana consumida principalmente en infusión, contiene varios fitocompuestos con efectos positivos demostrados sobre la salud de la piel y propiedades fotoprotectoras. La membrana de cáscara de huevo (ESM), un subproducto de la industria avícola, también presenta propiedades fotoprotectoras. Tanto la PI como la ESM contienen compuestos que absorben la radiación ultravioleta (RUV) y detienen los mecanismos por los que la RUV daña la piel. Merece la pena investigar los efectos sinérgicos de estos productos naturales en la reparación de la estructura de la piel y la producción de colágeno dérmico.

Objetivos: Determinar en qué medida la suplementación oral de IP y ESM, administrados individualmente o en combinación, promueve efectos beneficiosos sobre la piel de ratas Wistar maduras.

Métodos: Se caracterizó la composición química de IP y ESM y el factor de protección solar (SPF) espectrofotométrico del extracto de IP. In vitro, se evaluaron los efectos antioxidantes y anti-inflamatorios utilizando eritrocitos. La investigación in vivo consistió en el análisis y diagnóstico por imagen macro y microscópica de la piel de la región dorsal de ratas.

Resultados: El extracto IP mostró una baja capacidad SPF combinada con un efecto protector contra la hemólisis eritrocitaria inducida por AAPH. El extracto IP inhibió la hemólisis eritrocitaria inducida tanto por solución hipotónica como por calor. La actividad antioxidante y anti-inflamatoria de IP podría explicarse por sus propiedades estabilizadoras de la membrana. El análisis histológico mostró un aumento del contenido de colágeno de la piel de las ratas suplementadas. Cuando se administraron conjuntamente IP y ESM se produjo un claro aumento sinérgico de los niveles de colágeno.

Conclusiones: IP y ESM son beneficiosos para la salud de la piel, presentan efectos sinérgicos y podrían utilizarse como ingredientes en cosméticos orales.

Palabras Clave: capacidad quimiopreventiva; propiedad estabilizadora de la membrana; estructura de la piel.

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Citation Format: Ramirez MR, Rintoul I, Leiva M, Molli S, Yori JC (2023) Oral supplementation of Ilex paraguariensis extract and eggshell membrane exhibit beneficial effects on the skin of mature male rats. J Pharm Pharmacogn Res 11(2): 216–228. https://doi.org/10.56499/jppres22.1509_11.2.216
References

Aitdafoun M, Mounier C, Heymans F, Binisti C, Bon C, Godfroid JJ (1996) 4-Alkoxybenzamidines as new potent phospholipase A2 inhibitors. Biochem Pharmacol 51: 737-742. https://doi.org/10.1016/0006-2952(95)02172-8

AOAC (2000) Official methods of analysis 17th ed. Gaithersburg, MD, USA: Association of Official Analytical Chemists.

Argentina Pharmacopoeia (2013) volume VI, 7º Ed. pp 239.

Barg M,Rezin GT, Leffa DD, Balbinot F, Gomes LM, Carvalho-Silva M, Vuolo F, Petronilho F, Dal-Pizzol F, Streck V, Andrade M (2014) Evaluation of the protective effect of Ilex paraguariensis and Camellia sinensis extractson the prevention of oxidative damage caused by ultraviolet radiation. EnvironToxicol Pharmacol 37: 195-201. https://doi.org/10.1016/j.etap.2013.11.028

Bojic M, Haas VS, Šaric D, Maleš C (2013) Determination of flavonoids, phenolic acids, and xanthines in mate tea (Ilex paraguariensis St.-Hil.). J Anal Methods Chem 2013: 658596. https://doi.org/10.1155/2013/658596

Costa S, Detoni C, Branco C, Botura M, Branco A (2015) In vitro photoprotective effects of Marcetia taxifolia ethanolic extract and its potential for sunscreen formulations. Braz J Pharmacogn 25: 413-418. https://doi.org/10.1016/j.bjp.2015.07.013

Creighton TE (1989) Protein Structure: A practical approach. Oxford, United Kingdom.

Culling CFA (1965) Hand Book of Histopathological Techniques. 2nd edition, London: Butterworth,.

FDA – Food and Drug Administration (2012) FDA sheds light on sunscreens. Available in: http://www.fda.gov/downloads/ForConsumers/ConsumerUpdates/UCM258910.pdf. [Consulted May 3 2018]

Ferreira Cuelho CH, Dias Alves GA, Ortiz Lovatto M, Bonilha IF, Barbisan F, Manica da Cruz IV, Marchesan Oliveira S, Fachinetto R, Scotti do Canto G, Manfron M (2018) Topical formulation containing Ilex Paraguariensis extract increases metalloproteinases and myeloperoxidase activities in mice exposed to UVB radiation. J Photochem Photobiol B Biol 189: 95-103. https://doi.org/10.1016/j.jphotobiol.2018.10.004

Filip R, Lotito SB, Ferraro G, Fraga CG (2000) Antioxidant activity of Ilex paraguariensis and related species. Nutr Res 20: 1437-1446. https://doi.org/10.1016/S0271-5317(00)80024-X

Frankel (1970) Gradwohl’s Clinical laboratory methods and diagnostic. 7ª Ed, vol 1, – Ed. Frankel, Reitman y Sonnenwirth, pp. 123.

International Guiding Principles for Biomedical Research Involving Animals (2012) CIOMS-ICLAS.

Isolabella S, Cogoi L, Lopes P, Anesini C, Ferraro G, Filip R (2010) Study of the bioactive compoundsvariation during yerba mate (Ilex paraguariensis) processing. Food Chem 122: 695-699. https://doi.org/10.1016/j.foodchem.2010.03.039

Jacques RA, Arruda EJ, Oliveira LCS, Oliveira AP, Dariva C, Oliveira JV, Camarao EB (2007) Influence of drying methods and agronomic variables on the chemical composition of mate tea leaves (Ilex paraguariensis A. St.-Hil) obtained from high-pressure CO2 extraction. J Agric Food Chem 55: 10081-10085. https://doi.org/10.1021/jf071544o

Mansur JS, Breder MNR, Mansur MCA, Azulay RD (1986) Determinação do fator de proteção solar por espectrofotometria. An Bras Dermatol 61: 121-124.

Matsuoka R, Kurihara H, Yukawa H, Sasahara R (2019) Eggshell membrane protein can be absorbed and utilized in the bodies of rats. BMC Res Notes 12: 258. https://doi.org/10.1186/s13104-019-4306-0

Mesquita M, Santos E, Kassuya CA, Salvador MJ (2021) Chimarrao, terere and mate-tea in legitimate technology modes of preparation and consume: A comparative study of chemical composition, antioxidant, anti-inflammatory and anti-anxiety properties of the mostly consumed beverages of Ilex paraguariensis St. Hil. J Ethnopharmacol 279: 114401. https://doi.org/10.1016/j.jep.2021.114401

Michalak M, Pierzak M, Krecisz B, Suliga E (2021) Bioactive compounds for skin health: A review. Nutrients 13: 203. https://doi.org/10.3390/nu13010203

Miksık I, Eckhardt A, Sedlakova P, Mikulikova K (2007) Proteins of insoluble matrix of avian (Gallus gallus) eggshell. Connect Tissue Res 48: 1-8. https://doi.org/10.1080/03008200601003116

Muller C, Enomoto E, Buono A, Steiner JM, Lascelles BDX (2019) Placebo-controlled pilot study of the effects of an eggshell membrane-based supplement on mobility and serum biomarkers in dogs with osteoarthritis. Vet J 253: 105379. https://doi.org/10.1016/j.tvjl.2019.105379

Nur S, Angelina AA, Aswad M, Yulianty R, Burhan A, Nursamsiar (2021) In vitro anti-aging activity of Muntingia calabura L. fruit extract and its fraction. J Pharm Pharmacogn Res 9(4): 409-421. https://doi.org/10.56499/jppres20.979_9.4.409

Ohto-Fujita E, Konno T, Shimizu M, Ishihara K, Sugitate T, Miyake J, Yoshimura K, Taniwaki K, Sakurai T, Hasebe Y, Atomi Y (2011) Hydrolyzed eggshell membrane immobilized on phosphorylcholine polymer supplies extracellular matrix environment for human dermal fibroblasts. Cell Tissue Res 345: 177-190. https://doi.org/10.1007/s00441-011-1172-z

Pagano M, Faggio C (2015) The use of erythrocyte fragility to assess xenobiotic cytotoxicity. Cell Biochem Funct 33: 351-355. https://doi.org/10.1002/cbf.3135

Ramirez MR, Apel MA, Raseira MCB, Zuanazzi JAS, Henriques AT (2011) Polyphenols content and evaluation of antichemotactic, antiedematogenic and antioxidant activities of Rubus sp. Cultivars. J Food Biochem 35: 1389-1397. https://doi.org/10.1111/j.1745-4514.2010.00457.x

Ramirez MR, Mohamad L, Alarcon-Segovia LC, Rintoul I (2022) Effect of processing on the nutritional quality of Ilex paraguariensis. Appl Sci 12: 2487. https://doi.org/10.3390/app12052487

Sayre RM, Agin PP, Levee GJ, Marlowe E (1979) Comparison of in vivo and in vitro testing of sunscreening formulas. Photochem Photobiol 29: 559-566. https://doi.org/10.1111/j.1751-1097.1979.tb07090.x

Schinella G, Neyret E, Cónsole G, Tournier H, Prieto JM, Ríos JL, Giner RM (2014) An aqueous extract of Ilex paraguariensis reduces carrageenan-induced edema and inhibits the expression of cyclooxygenase-2 and inducible nitric oxide synthase in animal models of inflammation. Planta Med 80: 961-968. https://doi.org/10.1055/s-0034-1382876

Shinde UA, Phadke AS, Nair AM, Mungantiwar AA, Dikshit VJ, Saraf MN (1999) Membrane stabilizing activity a possible mechanism of action for the anti-inflammatory activity of Cedrus deodara wood oil. Fitoterapia 70: 251-257. https://doi.org/10.1016/S0367-326X(99)00030-1

Stadelman WJ (2000) Encyclopedia of Food Science and Technology, 2nd Edn. ed F. J. Francis, p. 593-599.

Sung YY, Kim DS (2021) Eggshell membrane ameliorates hyperuricemia by increasing urate excretion in potassium oxonate-injected rats. Nutrients 13: 3323. https://doi.org/10.3390/nu13103323

Trinder PA (1969) Simple turbidimetric method for the determination of serum cholesterol. Ann Clin Biochem 6: 165-166. https://doi.org/10.1177/000456326900600505

Xie M, Chen G, Wan P, Dai Z, Hu B, Chen L, Ou S, Zeng X, Sun Y (2017) Modulating effects of dicaffeoylquinic acids from Ilex kudingcha on intestinal microecology in vitro. J Agric Food Chem 65: 10185-10196. https://doi.org/10.1021/acs.jafc.7b03992

Yi R, Zhang J, Sun P, Qian Y, Zhao X (2019) Protective effects of Kuding Tea (Ilex kudingcha C. J. Tseng) polyphenols on UVB-induced skin aging in SKH1 hairless mice. Molecules 24: 1016. https://doi.org/10.3390/molecules24061016

Yoo JH, Kim JK, Yang HJ, Park KM (2015) Effects of egg shell membrane hydrolysates on UVB-radiation-induced wrinkle formation in SKH-1 hairless mice. Korean J Food Sci An 35: 58-70. https://doi.org/10.5851/kosfa.2015.35.1.58

Young DS (1995) Effects of Drugs on Clinical Laboratory Tests. In AACC Press, 4th ed. S.

Zou CG, Agar NS, Jones GL (2001) Oxidative insult to human red blood cells induced by free radical initiator AAPH and its inhibition by a commercial antioxidant mixture. Life Sci 69: 75-86. https://doi.org/10.1016/s0024-3205(01)01112-2

© 2023 Journal of Pharmacy & Pharmacognosy Research

Anticancer activity of N-(4-t-butylbenzoyl)-N’-phenylthiourea

J. Pharm. Pharmacogn. Res., vol. 11, no. 2, pp. 208-215, March-April 2023.

DOI: https://doi.org/10.56499/jppres22.1508_11.2.208

Original Article

Anticancer activity of N-(4-t-butylbenzoyl)-N’-phenylthiourea: Molecular docking, synthesis, and cytotoxic activity in breast and cervical cancer cells

[Actividad anticancerígena de la N-(4-t-butilbenzoil)-N’-feniltiourea: acoplamiento molecular, síntesis y actividad citotóxica en células de cáncer de mama y de cuello uterino]

Dini Kesuma1, Aguslina Kirtishanti2*, Citra H.A. Makayasa1, I Gede A. Sumartha1

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

2Department of Clinical and Community Pharmacy, University of Surabaya, Surabaya, Indonesia.

*E-mail: aguslina@staff.ubaya.ac.id

Abstract

Context: N-(4-t-butylbenzoyl)-N’-phenylthiourea, a derivative compound of N-benzoyl-N’-phenylthiourea, has relatively high lipophilicity with the epidermal growth factor receptor and silent mating type information regulation-1 enzyme as its molecular targets.

Aims: To determine the anticancer activity of N-(4-t-butylbenzoyl)-N’-phenylthiourea as an in silico and in vitro anticancer candidate for the breast and cervical cancer.

Methods: In silico test was performed to predict the cytotoxic activity using AutoDock Vina. This activity was also measured in vitro using the Microculture Tetrazolium Technique assays of three cancer cells (MCF-7, T47D, and HeLa) and normal cells (Vero cells).

Results: In silico test predicted that N-(4-t-butylbenzoyl)-N’-phenylthiourea was more cytotoxic at epidermal growth factor receptor than silent mating type information regulation-1 receptor. In vitro tests showed it exhibited cytotoxic activities against MCF-7, T47D, and HeLa without harming Vero cells.

Conclusions: N-(4-t-butylbenzoyl)-N’-phenylthiourea has the potential as an anticancer candidate for breast and cervical cancers.

Keywords: breast cancer; cervical cancer;EGFR; N-(4-t-butylbenzoyl)-N’-phenylthiourea; SIRT1.

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Resumen

Contexto: La N-(4-t-butilbenzoil)-N’-feniltiourea, un compuesto derivado de la N-benzoil-N’-feniltiourea, tiene una lipofilia relativamente alta y tiene como dianas moleculares el receptor del factor de crecimiento epidérmico y la enzima de regulación silenciosa de la información de tipo apareamiento-1.

Objetivos: Determinar la actividad anticancerosa de la N-(4-t-butilbenzoil)-N’-feniltiourea como candidato anticanceroso in silico e in vitro para el cáncer de mama y de cuello uterino.

Métodos: Se realizó un ensayo in silico para predecir la actividad citotóxica utilizando AutoDock Vina. Esta actividad también se midió in vitro mediante ensayos con la técnica de microcultivo de tetrazolio en tres células cancerosas (MCF-7, T47D y HeLa) y células normales (células Vero).

Resultados: La prueba in silico predijo que la N-(4-t-butilbenzoil)-N’-feniltiourea era más citotóxica para el receptor del factor de crecimiento epidérmico que para el receptor de regulación-1 de la información de tipo apareamiento silencioso. Las pruebas in vitro mostraron que presentaba actividades citotóxicas contra las células MCF-7, T47D y HeLa sin dañar las células Vero.

Conclusiones: La N-(4-t-butilbenzoil)-N’-feniltiourea tiene potencial como candidato anticancerígeno para los cánceres de mama y de cuello uterino.

Palabras Clave: cáncer de mama; cáncer de cuello de útero; EGFR; N-(4-t-butilbenzoil)-N’-feniltiourea; SIRT1.

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Citation Format: 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
References

Barosi G, Besses C, Birgegard G, Briere J, Cervantes F, Finazzi G, Gisslinger H, Griesshammer M, Gugliotta L, Harrison C, Hasselbalch H, Lengfelder E, Reilly JT, Michiels JJ, Barbui T (2007) A unified definition of clinical resistance/intolerance to hydroxyurea in essential thrombocythemia: results of a consensus process by an international working group. Leukemia 21(2): 277–280. https://doi.org/10.1038/sj.leu.2404473

Campestre C, Agamennone M, Tortorella P, Preziuso S, Biasone A, Gavuzzo E, Pochetti G, Mazza F, Hiller O, Tschesche H, Consalvi V, Gallina C (2006) N-Hydoxyurea as zinc binding group in matrix metalloproteinase inhibition: mode of binding in a complex with MMP-8. Bioorg Med Chem Lett 16(1): 20–24. https://doi.org/10.1016/j.bmcl.2005.09.057

Clayden J, Greeves N, Warren S, Wothers P (2012) Organic Chemistry 2nd ed. New York: Oxford University Press.

Goodwin EC, DiMaio D (2000) Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways. Proc Natl Acad Sci USA 97(23): 12513–12518. https://doi.org/10.1016/10.1073/pnas.97.23.12513

Indonesia Ministry of Health (2019) Deteksi dini cegah kanker. https://www.kemkes.go.id/article/print/19020500001/deteksi-dini-cegah-kanker.html [Consulted May 11, 2022].

Jensen F (2007) Introduction to Computational Chemistry 2nd ed. Chichester: John Willey & Sons Ltd.

Kar A (2007) Medicinal Chemistry 4th ed. New Delhi: New Age International Ltd. Publishers.

Kesuma D, Nasyanka AL, Rudyanto M, Siswandono, Purwanto BT, Sumartha IGA (2020a) A prospective modification structure: the effect of lipophilic and electronic properties of N-(phenylcarbamothyoil)-benzamide derivatives on cytotoxic activity by in silico and in vitro assay with T47D cells. Rasāyan J Chem 13(3): 1914–1918. https://doi.org/10.31788/RJC.2020.1335694

Kesuma D, Siswandono, Purwanto BT, Rudyanto M (2018) Synthesis of N-(phenylcarbamothioyl)-benzamide derivatives and their cytotoxic activity against MCF-7 cells. J Chinese Pharm Sci 27(10): 696–702. https://doi.org/10.5246/jcps.2018.10.071

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

Koç A, Wheeler LJ, Mathews CK, Merrill GF (2004) Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP pools. J Biol Chem 279(1): 223–230. https://doi.org/10.1074/jbc.M303952200

Li HQ, Lv PC, Yan T, Zhu HL (2009) Urea derivatives as anticancer agents. Anticancer Agents Med Chem 9(4): 471–480. https://doi.org/10.2174/1871520610909040471

Li HQ, Yan T, Yang Y, Shi L, Zhou CF, Zhu HL (2010) Synthesis and structure-activity relationships of N-benzyl-(X-2-hydroxybenzyl)-N’-phenylureas and thioureas as antitumor agents. Bioorg Med Chem 18(1): 305–313. https://doi.org/10.1016/j.bmc.2009.10.054

Li J, Tan JZ, Chen LL, Zhang J, Shen X, Mei CL, Fu LL, Lin LP, Ding J, Xiong B, Xiong XS, Liu H, Luo XM, Jiang HL (2006) Design, synthesis and antitumor evaluation of new series of N-substituted-thiourea derivatives. Acta Pharm Sin 27(9): 1259–1271. https://doi.org/10.1111/j.1745-7254.2006.00437.x

McMurry JM (2011) Fundamental of Organic Chemistry 7th ed. Belmont: Brooks/Cole.

Ong ALC, Ramasamy TS (2018) Role of sirtuin1-p53 regulatory axis in aging, cancer and cellular reprogramming. Ageing Res Rev 43: 64–80. https://doi.org/10.1016/j.arr.2018.02.004

Pavia DL, Lampman GM, Kriz GS, James R, Vyvyan JR (2009) Spectroscopy 4th ed. Belmont: Brooks/Cole.

Purwanto BT, Siswandono, Kesuma D, Widiandani T, Siswanto I (2021) Molecular modeling, ADMET prediction, synthesis and the cytotoxic activity from the novel N-(4-tert-butylphenylcarbamoyl)benzamide against Hela. Rasāyan J Chem 14(2): 1341–1350. https://doi.org/10.31788/RJC.2021.1426196

Qiu G, Li X, Che X, Wei C, He S, Lu J, Jia Z, Pang K, Fan L (2015) SIRT1 is a regulator of autophagy: Implications in gastric cancer progression and treatment. FEBS Lett 589(16): 2034–2042. https://doi.org/10.1016/j.febslet.2015.05.042

Rashidi M, Seghatoleslam A, Namavari M, Amiri A, Fahmidehkar MA, Ramezani A, Eftekhar E, Hosseini A, Erfani N, Fakher S (2017) Selective cytotoxic and apoptosis-induction of Cyrtopodion scabrum extract against digestive cancer cell lines. Int J Cancer Manag 10(5): e8633. https://doi.org/10.5812/ijcm.8633

Satria D, Silalahi J, Haro G, Ilyas S, Hasibuan PAZ (2019) Chemical analysis and cytotoxic activity of n-hexane fraction of Zanthoxylum acanthopodium DC. Fruits. Rasāyan J Chem 12(2): 803–808. https://doi.org/10.31788/RJC.2019.1225180

Schafer JM, Lee ES, O’Regan RM, Yao K, Jordan VC (2000) Rapid development of tamoxifen-stimulated mutant p53 breast tumors (T47D) in athymic mice. Clin Cancer Res 6(11): 4373–4380.

Siswandono (2016) Kimia Medisinal I Edisi 2. Surabaya: Airlangga University Press.

Tartarone A, Lazzari C, Lerose R, Conteduca V, Improta G, Zupa A, Bulotta A, Aieta M, Gregorc V (2013) Mechanisms of resistance to EGFR tyrosine kinase inhibitors gefitinib/erlotinib and to ALK inhibitor crizotinib. Lung Cancer 81(3): 328–336. https://doi.org/10.1016/j.lungcan.2013.05.020

Tibes R, Mesa RA (2011) Blood consult: resistant and progressive essential thrombocythemia. Blood 118(2): 240–242. https://doi.org/10.1182/blood-2011-01-327213

© 2023 Journal of Pharmacy & Pharmacognosy Research

Calcitonin nanostructured lipid carrier-based emulgel

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 198-207, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1538_11.1.198

Original Article

Advance in transdermal delivery of calcitonin using nanostructured lipid carrier-based emulgel

[Avance en la administración transdérmica de calcitonina mediante un emulgel nanoestructurado basado en un portador lipídico]

Zahrotunisa, Silvia Surini*

Laboratory of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Indonesia, Depok, West Java, 16424, Indonesia.

*E-mail: silvia@farmasi.ui.ac.id

Abstract

Context: Peptide-protein drugs have a very important role as therapeutic agents for various diseases. However, their therapeutic use has many barriers to delivery, such as large molecular weight, reduced stability during the manufacturing process and storage, and poor absorption when administered orally. One of peptide-protein drugs is calcitonin, a polypeptide of 32 amino acids used to overcome high levels of calcium in the blood, such as hyperparathyroidism. Nevertheless, drug delivery is still challenging to develop.

Aims: To evaluate a calcitonin nanostructured lipid carrier-based emulgel, which could penetrate through the stratum corneum, and meet the stability requirements.

Methods: Four formulas of calcitonin nanostructured lipid carrier (NLC) were prepared by the double emulsion-evaporation method, then all formulas were characterized in terms of particle size, polydispersity index, zeta potential, entrapment efficiency, and particle morphology. Calcitonin NLCs were then formulated into NLC-based emulgel. Further, in vitro penetration and stability of NLC calcitonin emulgel studies were conducted.

Results: The 75:1 ratio of total lipid to the drug (F2) was optimal for calcitonin-loaded NLC with a particle size of 135.6 nm, an index polydispersity of 0.1, the zeta potential of 34.7 mV, and an entrapment efficiency of 99.6%. According to the percutaneous penetration study, the calcitonin NLC-based-emulgel resulted in a fivefold enhancement compared to the non-NLC calcitonin emulgel. Moreover, the stability study illustrated calcitonin levels after six months were 46.09-60.95% and 43.45-68.59% at storage conditions of 5 ± 3ºC and 25 ± 2ºC/RH 60 ±5 %, respectively.

Conclusions: The calcitonin NLC-based-emulgel produced a fivefold enhancement permeation through the stratum corneum.

Keywords: calcitonin; emulgel; nanostructured lipid carrier; peptide-protein drug; transdermal.

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Resumen

Contexto: Los fármacos péptido-proteicos desempeñan un papel muy importante como agentes terapéuticos para diversas enfermedades. Sin embargo, su uso terapéutico presenta muchas barreras para su administración, como un gran peso molecular, una estabilidad reducida durante el proceso de fabricación y el almacenamiento, y una absorción deficiente cuando se administran por vía oral. Uno de los fármacos péptido-proteicos es la calcitonina, un polipéptido de 32 aminoácidos que se utiliza para superar los niveles elevados de calcio en sangre, como en el hiperparatiroidismo. Sin embargo, la administración del fármaco sigue siendo difícil de desarrollar.

Objetivos: Evaluar un emulgel nanoestructurado a base de un portador lipídico de calcitonina, que pueda penetrar a través del estrato córneo y cumplir los requisitos de estabilidad.

Métodos: Se prepararon cuatro fórmulas de portador lipídico nanoestructurado (NLC) de calcitonina por el método de doble emulsión-evaporación, y luego se caracterizaron todas las fórmulas en términos de tamaño de partícula, índice de polidispersidad, potencial zeta, eficiencia de atrapamiento y morfología de partícula. A continuación, las NLC de calcitonina se formularon en emulgeles basados en NLC. Además, se realizaron estudios de penetración y estabilidad in vitro del emulgel de NLC de calcitonina.Resultados: La relación 75:1 entre el lípido total y el fármaco (F2) fue óptima para la NLC cargada de calcitonina, con un tamaño de partícula de 135,6 nm, un índice de polidispersidad de 0,1, un potencial zeta de 34,7 mV y una eficiencia de atrapamiento del 99,6%. Según el estudio de penetración percutánea, el emulgel de calcitonina basado en NLC quintuplicó la eficacia del emulgel de calcitonina sin NLC. Además, el estudio de estabilidad ilustró que los niveles de calcitonina después de seis meses eran del 46,09-60,95% y del 43,45-68,59% en condiciones de almacenamiento de 5 ± 3ºC y 25 ± 2ºC/RH 60 ± 5%, respectivamente.

Conclusiones: El emulgel a base de NLC de calcitonina produjo una permeación cinco veces mayor a través del estrato córneo.

Palabras Clave: calcitonina; emulgel; fármaco péptido-proteico; portador lipídico nanoestructurado; transdérmica.

jppres_pdf_free

Citation Format: Zahrotunisa, Surini S (2023) Advance in transdermal delivery of calcitonin using nanostructured lipid carrier-based emulgel. J Pharm Pharmacogn Res 11(1): 198–207. https://doi.org/10.56499/jppres22.1538_11.1.198
References

Arunprasert K, Pornpitchanarong C, Piemvuthi C, Siraprapapornsakul S, Sripeangchan S, Lertsrimongkol O, Patrojanasophon, P (2022) Nanostructured lipid carrier-embedded polyacrylic acid transdermal patches for improved transdermal delivery of capsaicin. Eur J Pharm Sci 173: 106169. https://doi.org/10.1016/j.ejps.2022.106169

Azmi NA, Hasham R, Ariffin FD, Elgharbawy AA, Salleh HM (2020) Characterization, stability assessment, antioxidant evaluation and cell proliferation activity of virgin coconut oil-based nanostructured lipid carrier loaded with Ficus deltoidea extract. Cosmetics 7(4): 83. https://doi.org/10.3390/cosmetics7040083

Chang SL, Hofmann GA, Zhang L, Deftos LJ, Banga AK (2003) Stability of a transdermal salmon calcitonin formulation. Drug Deliv 10(1): 41–45. https://doi.org/10.1080/713840326

Chen C, Fan T, Jin Y, Zhou Z, Yang Y, Zhu X, Huang Y (2013) Orally delivered salmon calcitonin-loaded solid lipid nanoparticles prepared by micelle-double emulsion method via the combined use of different solid lipids. Nanomedicine 8(7): 1085-1100. https://doi.org/10.2217/nnm.12.141

Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Mozafari MR (2018) Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 10(2): 57. https://doi.org/10.3390/pharmaceutics10020057

Felsenfeld AJ, Levine BS (2015) Calcitonin, the forgotten hormone: Does it deserve to be forgotten? Clin Kidney J 8(2): 180–187. https://doi.org/10.1093/ckj/sfv011

Findlay DM, Sexton PM (2004) Calcitonin. Growth Factors 22(4): 217–224. https://doi.org/10.1080/08977190410001728033

Garcia-Fuentes M, Torres D, Alonso MJ (2005) New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin. Int J Pharm 296(2): 122-132. https://doi.org/10.1016/j.ijpharm.2004.12.030

Gu Y, Yang M, Tang X, Wang T, Yang D, Zhai G, Liu J (2018) Lipid nanoparticles loading triptolide for transdermal delivery: Mechanisms of penetration enhancement and transport properties. J Nanobiotechnology 16: 68. https://doi.org/10.1186/s12951-018-0389-3

Hassan DH, Shohdy JN, El-Setouhy DA, El-Nabarawi M, Naguib MJ (2022) Compritol-based nanostrucutured lipid carriers (NLCs) for augmentation of zolmitriptan bioavailability via the transdermal route: In vitro optimization, ex vivo permeation, in vivo pharmacokinetic study. Pharmaceutics 14(7): 1484. https://doi.org/10.3390/pharmaceutics14071484

ICH (2003) Q1A (R2) Stability Testing of New Drug Substances and Products. ICH harmonised tripartite guideline. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.

Leonyza A, Surini S (2019) Optimization of sodium deoxycholate-based transfersomes for percutaneous delivery of peptides and proteins. Int J App Pharm 11(5): 329-332. https://doi.org/10.22159/ijap.2019v11i5.33615

Manosroi A, Chankhampan C, Manosroi W, Manosroi J (2012) Enhancement of chemical stability and transdermal absorption of salmon calcitonin loaded in elastic niosomes. Adv Sci Lett 5(1): 314–319. https://doi.org/10.1166/asl.2012.2002

Manosroi J, Lohcharoenkal W, Götz F, Werner RG, Manosroi W, Manosroi A (2011) Transdermal absorption enhancement of N-Terminal Tat–GFP Fusion Protein (TG) loaded in novel low-toxic elastic anionic niosomes. J Pharm Sci 100(4): 1525–1534. https://doi.org/10.1002/jps.22355

Manosroi J, Lohcharoenkal W, Götz F, Werner RG, Manosroi W, Manosroi A (2013) Transdermal absorption and stability enhancement of salmon calcitonin by Tat peptide. Drug Dev Ind Pharm 39(4): 520–525. https://doi.org/10.3109/03639045.2012.684388

Martenka EA (2018) Encapsulation of fluorogenic probes and pharmacologically active molecules into nanoparticles for enhancing cellular uptake. PhD Thesis, Université Henri Poincaré, Nancy, Polandia.

Martihandini N, Surini S, Bahtiar A (2021) Andrographolide-loaded ethosomal gel for transdermal application: Formulation and in vitro penetration study. Pharm Sci 28(3): 470–480. https://doi.org/10.34172/ps.2021.76

Mendes IT, Ruela AL, Carvalho FC, Freitas JT, Bonfilio R, Pereira GR (2019) Development and characterization of nanostructured lipid carrier-based gels for the transdermal delivery of donepezil. Colloids Surf B 1: 274–281. https://doi.org/10.1016/j.colsurfb.2019.02.007

Pardeike J, Hommoss A, Müller RH (2009) Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm 366(2):170–184. https://doi.org/10.1016/j.ijpharm.2008.10.003

Patton K, Borshoff DC (2018) Adverse drug reactions. Anaesthesia 73(1): 76–84. https://doi.org/10.1111/anae.14143

Sikora A, Bartczak D, Geißler D, Kestens V, Roebben G, Ramaye Y, Minelli C (2015) A systematic comparison of different techniques to determine the zeta potential of silica nanoparticles in biological medium. Anal Methods 7(23): 9835–9843. https://doi.org/10.1039/c5ay02014j

Suhaimi SH, Hasham R, Rosli NA (2015) effects of formulation parameters on particle size and polydispersity index of Orthosiphon stamineus loaded nanostructured lipid carrier. J Adv Res App Sci Eng Tech 1: 36–39.

Surini S, Leonyza A, Suh CW (2020) Formulation and in vitro penetration study of recombinant human epidermal growth factor-loaded transfersomal emulgel. Adv Pharm Bull 10(4): 586–594. https://doi.org/10.34172/apb.2020.070

Svarc F, Hermida L (2020) Transdermal and bioactive nanocarriers for skin care. In: Nanocosmetics: Fundamentals, applications and toxicity 1st edn. Elsevier, Amsterdam, Netherlands: Radarweg, pp: 35-58. https://doi.org/10.1016/B978-0-12-822286-7.00003-6

Tas C, Mansoor S, Banga AK., Prausnitz MR (2012) Development and validation of a rapid isocratic RP-HPLC method for the quantification of salmon calcitonin. Turk J Pharm Sci 9: 323–334.

Teeranachaideekul V, Boribalnukul P, Morakul B, Junyaprasert VB (2022) Influence of vegetable oils on in vitro performance of lutein-loaded lipid carriers for skin delivery: Nanostructured lipid carriers vs. nanoemulsions. Pharmaceutics 14(10): 2160. https://doi.org/10.3390/pharmaceutics14102160

Torres-Lugo M, Peppas NA (2000) Transmucosal delivery systems for calcitonin: A review. Biomaterials 21(12): 1191–1196. https://doi.org/10.1016/s0142-9612(00)00011-9

Vitorino C, Sousa J, Pais A (2015) Overcoming the skin permeation barrier: Challenges and opportunities. Curr Pharm Des 21(20): 2698–2712. https//doi.org/10.2174/1381612821666150428124053

Wimalawansa SJ (2018) Physiology of calcitonin and its therapeutic uses. In: Encyclopedia of endocrine diseases 2nd edn. Edited by Ilpo H. Academic press, Cambridge, USA: Massachusetts, pp: 178–191. https://doi.org/10.1016/b978-0-12-801238-3.95758-1

Zeb A, Arif ST, Malik M, Shah FA, Din FU, Qureshi OS, Kim JK (2019) Potential of nanoparticulate carriers for improved drug delivery via skin. Int J Pharm Investig 49: 485-517. https://doi.org/10.1007/s40005-018-00418-8

Zhang Y, Ng W, Feng X, Cao F, Xu H (2017) Lipid vesicular nanocarrier: Quick encapsulation efficiency determination and transcutaneous application. Int J Pharm 516(2): 225–230. https://doi.org/10.1016/j.ijpharm.2016.11.011

© 2023 Journal of Pharmacy & Pharmacognosy Research

Anti-leukemic activity of Cyperus rotundus

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 191-197, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1502_11.1.191

Original Article

Anti-leukemic activity of Cyperus rotundus L.on human acute myeloid leukemia HL-60 cells in vitro

[Actividad antileucémica de Cyperus rotundus L. sobre células humanas de leucemia mieloide aguda HL-60 in vitro]

Sulistyo Mulyo Agustini1, Edi Widjajanto2, Muhaimin Rifa’i3, Sofia Mubarika Haryana4, Nurdiana5, Diana Lyrawati5, Usi Sukorini6, Noviana Dwi Lestari7*

1Department of Pathology, Faculty of Medicine, Muhammadiyah Malang University, Malang, East Java, Indonesia.

2Department of Clinical Pathology, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia.

3Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, East Java, Indonesia.

4Department of Histology and Cell Biology, Faculty of Medicine, Gadjah Mada University, Indonesia.

5School of Pharmacy, Faculty of Medicine, Brawijaya University, Malang, Indonesia.

6Department of Clinical Pathology, Medical Faculty, Gadjah Mada University, Yogyakarta, Indonesia.

7Medical Education Study Program, Faculty of Medicine, Muhammadiyah Malang University, Malang, Indonesia.

*E-mail: novianalestari@umm.ac.id; novianadwi.lestari@yahoo.co.id

Abstract

Context: Acute myeloid leukemia (AML) is the most common form of acute leukemia. Currently, many people use medicinal herbs for the treatment of cancers. Nut grass (Cyperus rotundus L.) is a medicinal plant widely used in conventional medicine due to its role as an anti-cancer.

Aims: To evaluate the effect of Cyperus rotundus tuber (CRT) ethanolic extract on cell proliferation, differentiation, cell cycle, and apoptotic of HL-60 cells.

Methods: HL-60 cells line as a model for AML was cultured under the influence of CRT extract concentrations (35.4, 354, and 3540 µg/mL) for 48 h. Furthermore, the cell was subjected to carboxyfluorescein succinimidyl ester staining for proliferation, using a CD117 marker for differentiation. Annexin V-FITC and PI for cell cycle and apoptosis. The effect of this herb was studied by flow cytometry. The data were statistically analyzed with one-way ANOVA (p≤0.05) and the Tukey test using SPSS version 16 for Windows.

Results: The results showed that the CRT inhibited proliferation activity, differentiation, cell cycle arrest, and apoptosis.

Conclusions: The data clearly showed the potential anti-cancer activity of CRT on HL-60 cells and suggested that it could help develop promising therapeutic agents for AML treatments.

Keywords: acute myeloid leukemia; apoptosis; cell cycle; Cyperus rotundus; HL-60 cells line.

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Resumen

Contexto: La leucemia mieloide aguda (LMA) es la forma más común de leucemia aguda. En la actualidad, muchas personas utilizan hierbas medicinales para el tratamiento de los cánceres. La hierba de la nuez (Cyperus rotundus L.) es una planta medicinal ampliamente utilizada en la medicina convencional debido a su papel como anticancerígeno.

Objetivos: Evaluar el efecto del extracto etanólico del tubérculo de Cyperus rotundus (CRT) sobre la proliferación celular, la diferenciación, el ciclo celular y la apoptosis de las células HL-60.

Métodos: Se cultivó la línea celular HL-60 como modelo de LMA bajo la influencia de concentraciones de extracto de CRT (35,4; 354 y 3540 µg/mL) durante 48 h. Además, las células se sometieron a tinción con éster succinimidílico de carboxifluoresceína para la proliferación, y con un marcador CD117 para la diferenciación. Annexin V-FITC y PI para el ciclo celular y la apoptosis. El efecto de este extracto se estudió mediante citometría de flujo. Los datos se analizaron estadísticamente con ANOVA unidireccional (p≤0,05) y la prueba de Tukey utilizando SPSS versión 16 para Windows.

Resultados: Los resultados mostraron que el CRT inhibió la actividad de proliferación, diferenciación, detención del ciclo celular y apoptosis.

Conclusiones: Los datos mostraron claramente la potencial actividad anticancerígena del CRT en células HL-60 y sugirieron que podría ayudar a desarrollar agentes terapéuticos prometedores para tratamientos de LMA.

Palabras Clave: apoptosis; células HL-60; ciclo celular; Cyperus rotundus; leucemia mieloide aguda.

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Citation Format: Agustini SM, Widjajanto E, Rifa’i M, Haryana SM, Nurdiana, Lyrawati D, Sukorini U, Lestari ND (2023) Anti-leukemic activity of Cyperus rotundus L. on human acute myeloid leukemia HL-60 cells in vitro. J Pharm Pharmacogn Res 11(1): 191–197. https://doi.org/10.56499/jppres22.1502_11.1.191
References

Abo-Altemen RA, Al-Shammari AM, Shawkat MS (2019) GC-MS analysis and chemical composition identification of Cyperus rotundus L. from Iraq. Energy Procedia 157: 1462–1474. https://doi.org/10.1016/j.egypro.2018.11.311

Arnone M, Konantz M, Hanns P, Stanger AMP, Bertels S, Godavarthy PS, Christopeit M, Lengerke C (2020) Acute myeloid leukemia stem cells: The challenges of phenotypic heterogeneity. Cancers 12: 3742. https://doi.org/10.3390/cancers12123742

Babiaka SB, Moumbock AFA, Günther S, Ntie-Kang F (2021) Natural products in Cyperus rotundus L. (Cyperaceae): An update of the chemistry and pharmacological activities. RSC Adv 11: 15060–15077. https://doi.org/10.1039/d1ra00478f

Badgujar SB, Bandivdekar AH (2015) Evaluation of a lactogenic activity of an aqueous extract of Cyperus rotundus Linn. J Ethnopharmacol 163: 39–42. https://doi.org/10.1016/j.jep.2015.01.019

Bajpay A, Nainwal RC, Singh D, Tewari SK (2018) Medicinal value of Cyperus rotundus Linn: An updated review. Med Plants – Int J Phytomedicines Relat Ind 10: 165–170. https://doi.org/10.5958/0975-6892.2018.00027.8

Bashmail HA, Alamoudi AA, Noorwali A, Hegazy GA, AJabnoor GM, Al-Abd AM (2020) Thymoquinone enhances paclitaxel anti-breast cancer activity via inhibiting tumor-associated stem cells despite apparent mathematical antagonism. Molecules 25: 426. https://doi.org/10.3390/molecules25020426

Gupta A, Shah K, Oza MJ, Behl T (2019) Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment. Biomed Pharmacother 109: 484–492. https://doi.org/10.1016/j.biopha.2018.10.155

Gupta RK, Banerjee A, Pathak S, Sharma C, Singh N (2013) Induction of mitochondrial-mediated apoptosis by Morinda citrifolia (noni) in human cervical cancer cells. Asian Pac J Cancer Prev 14: 237–242. https://doi.org/10.7314/apjcp.2013.14.1.237

Kabel A, Zamzami F, Al-Talhi M, Al-Dwila K, Hamza R (2017) Acute myeloid leukemia: A focus on risk factors, clinical presentation, diagnosis and possible lines of management. J Cancer Res Treat 5: 62–67. https://doi.org/10.12691/jcrt-5-2-4

Karacaer NT (2022) In vitro and in silico evaluation of thymoquinone as potential anti-cancer agent in human acute myeloid leukemia HL-60 cells. Trak Univ J Nat Sci 23: 53–63. https://doi.org/10.23902/trkjnat.999403

Kilani S, Ben Sghaier M, Limem I, Bouhlel I, Boubaker J, Bhouri W, Skandrani I, Neffatti A, Ben Ammar R, Dijoux-Franca MG, Ghedira K, Chekir-Ghedira L (2008) In vitro evaluation of antibacterial, antioxidant, cytotoxic and apoptotic activities of the tubers infusion and extracts of Cyperus rotundus. Bioresour Technol 99: 9004–9008. https://doi.org/10.1016/j.biortech.2008.04.066

Majolo F, de Oliveira Becker Delwing LK, Marmitt DJ, Bustamente-Filhoc IC, Goettert MI (2019) Medicinal plants and bioactive natural compounds for cancer treatment: Important advances for drug discovery. Phytochem Lett 31: 196–207. https://doi.org/10.1016/j.phytol.2019.04.003

Niu G, Yin S, Xie S, Li Y, Nie D, Ma L, Wang X, Wu Y (2011) Quercetin induces apoptosis by activating caspase-3 and regulating Bcl-2 and cyclooxygenase-2 pathways in human HL-60 cells. Acta Biochim Biophys Sin 43: 30–37. https://doi.org/10.1093/abbs/gmq107

Park SE, Shin WT, Park C, Hong SH, Kim GY, Kim SO, Ryu CH, Hong SH, Choi YH (2014) Induction of apoptosis in MDA-MB-231 human breast carcinoma cells with an ethanol extract of Cyperus rotundus L. by activating caspases. Oncol Rep 32: 2461–2470. https://doi.org/10.3892/or.2014.3507

Rashidi Z, Khosravizadeh Z, Talebi A, Khodamoradi K, Ebrahimi R, Amidi F (2021) Overview of biological effects of quercetin on ovary. Phytother Res 35: 33–49. https://doi.org/10.1002/ptr.6750

Rice KL, de Thé H (2014) The acute promyelocytic leukaemia success story: Curing leukaemia through targeted therapies. J Intern Med 276: 61–70. https://doi.org/10.1111/joim.12208

Rubio C, Mendoza C, Trejo C, Custodio V, Rubio-Osornio M, Hernández L, González E, Paz C (2019) Activation of the extrinsic and intrinsic apoptotic pathways in cerebellum of kindled rats. Cerebellum 18: 750–760. https://doi.org/10.1007/s12311-019-01030-8

Samarghandian S, Azimi-Nezhad M, Farkhondeh T (2019) Thymoquinone-induced antitumor and apoptosis in human lung adenocarcinoma cells. J Cell Physiol 234: 10421–10431. https://doi.org/10.1002/jcp.27710

Sayed HM, Mohamed MH, Farag SF, Mohamed GA, Proksch P (2007) A new steroid glycoside and furochromones from Cyperus rotundus L. Nat Prod Res 21: 343–350. https://doi.org/10.1080/14786410701193056

Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65: 5–29. https://doi.org/10.3322/caac.21254

Simorangkir D, Masfria M, Harahap U, Satria D (2019) Activity anti-cancer n-hexane fraction of Cyperus rotundus L. rhizome to breast cancer MCF-7 cell line. Open Access Maced J Med Sci 7: 3904–3906. https://doi.org/10.3889/oamjms.2019.530

Srivastava S, Somasagara RR, Hegde M, Nishana M, Tadi SK, Srivastava M, Choudhary B, Raghavan SC (2016) Quercetin, a natural flavonoid interacts with DNA, arrests cell cycle and causes tumor regression by activating mitochondrial pathway of apoptosis. Sci Rep 6: 24049. https://doi.org/10.1038/srep24049

Subramaniam S, Selvaduray KR, Radhakrishnan AK (2019) Bioactive compounds: Natural defense against cancer? Biomolecules 9(12): 758. https://doi.org/10.3390/biom9120758

Susianti S (2009) Cytotoxic effect of purple nut sedge tuber (Cyperus rotundus L.) methanol and chloroform extract on HeLa and SiHa cells. Yogyakarta: PAAI.

Tuorkey MJ (2016) Molecular targets of luteolin in cancer. Eur J Cancer Prev 25: 65–76. https://doi.org/10.1097/CEJ.0000000000000128

Ullah MA, Hassan A (2022) Medical treatment of various diseases through nagarmotha (Cyperus rotundus) plant. Eur J Biol Med Sci Res 10: 26–43. https://doi.org/10.37745/ejbmsr/vol10.no1.pp26-43

Yan L, Shen J, Wang J, Yang X, Dong S, Lu S (2020) Nanoparticle-based drug delivery system: A patient-friendly chemotherapy for oncology. Dose-Response 18: 1–12. https://doi.org/10.1177/1559325820936161

Yohe S (2015) Molecular genetic markers in acute myeloid leukemia. J Clin Med 4: 460–478. https://doi.org/10.3390/jcm4030460

Zhang HW, Hu JJ, Fu RQ, Liu X, Zhang YH, Li J, Liu L, Li YN, Deng Q, Luo QS, Ouyang Q, Gao N (2018) Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells. Sci Rep 8: 11255. https://doi.org/10.1038/s41598-018-29308-7

© 2023 Journal of Pharmacy & Pharmacognosy Research

Moringa oleifera fungistatic effects on Candida albicans

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 179-190, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1533_11.1.179

Original Article

Fungistatic effect of Moringa oleifera Lam. on the metabolism changes of Candida albicans

[Efecto fungistático de Moringa oleifera Lam. sobre los cambios en el metabolismo de Candida albicans]

Basri A. Gani1*, Cut Soraya2, Vinna Kurniawati Sugiaman3, Fitri Yunita Batubara4, Dharli Syafriza5, Silvia Naliani6, Sri Rezeki7, Subhani Jakfar8, Muhammad Nazar9, Kemala Hayati10

1Department of Oral Biology, Denstistry Faculty, Universitas Syiah Kuala. Jl., Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Indonesia.

2Department of Conservative Dentistry, Dentistry Faculty, Universitas Syiah Kuala. Jl. Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Indonesia.

3Department of Oral Biology, Dentistry Faculty, Universitas Kristen Maranatha. Jl. Prof. Drg. M.P.H. No. 65, Bandung, Jawa Barat, Indonesia.

4Department of Conservative Dentistry, Dentistry Faculty, Universitas Sumatera Utara, Jl. Alumni No.2, Kampus USU, Medan, Sumatera Utara, Indonesia.

5Department of Pedodontics, Dentistry Faculty, Universitas Syiah Kuala. Jl., Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Indonesia.

6Department of Prosthodontics, Dentistry Faculty, Universitas Kristen Maranatha. Jl. Prof. Drg. Surya Sumantri, M.P.H. No. 65, Bandung, Jawa Barat, Indonesia.

7Department of Oral Medicine, Dentistry Faculty, Universitas Syiah Kuala. Jl., Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Indonesia.

8Department of Dental Material, Denstistry Faculty, Universitas Syiah Kuala. Jl., Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Indonesia.

9Department of Chemistry Education, Faculty of Teacher and Training, Universitas Syiah Kuala.  Jl. Tgk. Hasan Krueng Kalee, Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Aceh, Indonesia.

10Department of Dental Radiology, Dentistry Faculty, Universitas Syiah Kuala. Jl. Kopelma Darussalam, Kecamatan Syiah Kuala, Kota Banda Aceh, Aceh. Indonesia.

*E-mail: basriunoe@unsyiah.ac.id

Abstract

Context: Candida albicans is a pathological agent that triggers oral candidiasis because C. albicans can adapt to changes to increase growth and adhesion through biofilm formation mechanisms. Moringa oleifera Lam. has been reported to have fungistatic properties and increases the metabolism change of C. albicans.

Aims: To evaluate the fungistatic effect of M. oleifera leaves ethanolic extract (MOLE) on the metabolism changes of C. albicans cells associated with growth and biofilm formation.

Methods: The assessment of metabolism changes (stress response and metabolic alterations) of C. albicans by the action of MOLE was performed by mean of FTIR, growth assessment by spectrophotometry, biofilm formation with 1% crystal violet, also read by spectrophotometry, and observation of biofilm mass with a microscope.

Results: MOLE showed substantial absorption values based on topological polar surface area (<140 Å2). Concentrations of 25% and 6.25% of MOLE increased the stress response (metabolism changes) of C. albicans (66-75%), meanwhile 50% and nystatin (100.000 IU/mL)were similar in inducing metabolism changes of C. albicans. All concentrations of M. oleifera could inhibit the growth of C. albicans at all incubation times (24, 48, and 72 h) with an Optical Density (OD) of 0.02-0.05 (<300 CFU/mL) and were able to degrade the biofilm formation of C. albicans on a scale substantial at 24 and 48 h (OD>0.4), and moderate scale at 72 h (OD 0.2-0.39).

Conclusions: The extract of M. oleifera has increased metabolism changes (stress response) of C. albicans cells, which correlate with the ability to inhibit growth and biofilm formation for 24, 48, and 72 h.

Keywords: biofilm; Candida albicans; fungistatic; growth; stress response.

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Resumen

Contexto: Candida albicans es un agente patológico que desencadena la candidiasis oral porque C. albicans puede adaptarse a los cambios para aumentar el crecimiento y la adhesión a través de mecanismos de formación de biopelículas. Se ha informado que Moringa oleifera Lam. tiene propiedades fungistáticas y aumenta el cambio de metabolismo de C. albicans.

Objetivos: Evaluar el efecto fungistático del extracto etanólico de hojas de M. oleifera (MOLE) sobre los cambios en el metabolismo de las células de C. albicans asociados con el crecimiento y la formación de biopelículas.

Métodos: La evaluación de los cambios en el metabolismo (respuesta al estrés y alteraciones metabólicas) de C. albicans por acción de MOLE fue realizada mediante FTIR, la evaluación del crecimiento mediante espectrofotometría, la formación de biofilm con cristal violeta al 1%, también leído mediante espectrofotometría, y la observación de la masa del biofilm con un microscopio.

Resultados: MOLE presentó valores de absorción sustanciales basados en el área de superficie polar topológica (<140 Å2). Las concentraciones de 25% y 6,25% de MOLEaumentaron la respuesta de estrés (cambios en el metabolismo) de C. albicans (66-75%), mientras que el 50% y la nistatina (100.000 UI/mL) fueron similares en la inducción de cambios en el metabolismo de C. albicans. Todas las concentraciones de M. oleifera pudieron inhibir el crecimiento de C. albicans en todos los tiempos de incubación (24, 48 y 72 h) con una densidad óptica (DO) de 0,02-0,05 (<300 ufc/mL) y fueron capaces de degradar la formación de biopelículas de C. albicans en una escala sustancial a las 24 y 48 h (DO>0,4), y moderada a las 72 h (DO 0,2-0,39).

Conclusiones: El extracto de M. oleifera ha aumentado los cambios en el metabolismo (respuesta al estrés) de las células de C. albicans, que se correlacionan con la capacidad de inhibir el crecimiento y la formación de biopelículas durante 24, 48 y 72 h.

Palabras Clave: biopelícula; Candida albicans; crecimiento; fungistático; respuesta al estrés.

jppres_pdf_free

Citation Format: Gani BA, Soraya C, Sugiaman VK, Batubara FY, Syafriza D, Naliani S, Rezeki S, Jakfar S, Nazar M, Hayati K (2023) Fungistatic effect of Moringa oleifera Lam. on the metabolism changes of Candida albicans. J Pharm Pharmacogn Res 11(1): 179–190. https://doi.org/10.56499/jppres22.1533_11.1.179
References

Abd Rani NZ, Husain K, Kumolosasi E (2018) Moringa genus: A review of phytochemistry and pharmacology. Front Pharmacol 9: 108. https://doi.org/10.3389/fphar.2018.00108

Alberga D, Trisciuzzi D, Montaruli M, Leonetti F, Mangiatordi GF, Nicolotti O (2018) A new approach for drug target and bioactivity prediction: The multifingerprint similarity search algorithm (mussel). J Chem Inf Model 59: 586–596. https://doi.org/10.1021/acs.jcim.8b00698

Alvarez-Ordonez A, Mouwen D, Lopez M, Prieto M (2011) Fourier transform infrared spectroscopy as a tool to characterize molecular composition and stress response in foodborne pathogenic bacteria. J Microbiol Methods 84: 369–378. https://doi.org/10.1016/j.mimet.2011.01.009

Araújo NM, Dias LP, Costa HP, Sousa DO, Vasconcelos IM, de Morais GA, Oliveira JT (2019) ClTI, a Kunitz trypsin inhibitor purified from Cassia leiandra Benth. seeds, exerts a candidicidal effect on Candida albicans by inducing oxidative stress and necrosis. Biochim Biophys Acta Biomembr 1861: 183032. https://doi.org/10.1016/j.bbamem.2019.183032

Asmah N, Suniarti DF, Bachtiar EW, Margono DA, Gani BA (2022) Chemical compounds anti-bacterial of Citrus aurantifolia ethanol extract to inhibit the early biofilm formation and growth of Enterococcus faecalis root canal isolate. Res J Pharm Technol 15: 2667–2674. https://doi.org/10.52711/0974-360X.2022.00446

Bickerton GR, Paolini GV, Besnard J, Muresan S, Hopkins AL (2012) Quantifying the chemical beauty of drugs. Nat Chem 4: 90–98. https://doi.org/10.1038/nchem.1243

Broseta D, Fredrickson GH, Helfand E, Leibler L (1990) Molecular weight and polydispersity effects at polymer-polymer interfaces. Macromolecules 23: 132–139. https://doi.org/10.1021/ma00203a023

Chae SY, Jang MK, Nah JW (2005) Influence of molecular weight on oral absorption of water soluble chitosans. J Control Release 102: 383–394. https://doi.org/10.1016/j.jconrel.2004.10.012

Chakraborty S, Majumder S, Ghosh A, Saha S, Bhattacharya M (2021) Metabolomics of potential contenders conferring antioxidant property to varied polar and non-polar solvent extracts of Edgaria darjeelingensis CB Clarke. Bull Natl Res Cent 45: 48. https://doi.org/10.1186/s42269-021-00503-3

Chen X, Zhang Z, Chen Z, Li Y, Su S, Sun S (2020) Potential antifungal targets based on glucose metabolism pathways of Candida albicans. Front Microbiol 11: 296. https://doi.org/10.3389/fmicb.2020.00296

Chen Y, Mallick J, Maqnas A, Sun Y, Choudhury BI, Côte P, Yan L, Ni TJ, Li Y, Zhang D, Rodríguez-Ortiz R (2018) Chemogenomic profiling of the fungal pathogen Candida albicans. Antimicrob Agents Chemother 62: e02365-17. https://doi.org/10.1128/AAC.02365-17

Czyrski A (2019) Determination of the lipophilicity of ibuprofen, naproxen, ketoprofen, and flurbiprofen with thin-layer chromatography. J Chem 2019: 3407091. https://doi.org/10.1155/2019/3407091

da Silva Neto JX, da Costa HPS, Vasconcelos IM, Pereira ML, Oliveira JTA, Lopes TDP, Dias LP, Araújo NMS, Moura LFWG, Van Tilburg MF (2020) Role of membrane sterol and redox system in the anti-candida activity reported for Mo-CBP2, a protein from Moringa oleifera seeds.Int J Biol Macromol 143: 814–824. https://doi.org/10.1016/j.ijbiomac.2019.09.142

Ercan K, Gecesefa OF, Taysi ME, Ali Ali OA, Taysi S (2021) Moringa oleifera: A review of its occurrence, pharmacological importance and oxidative stress. Mini Rev Med Chem 21: 380–396. https://doi.org/10.2174/1389557520999200728162453

Fulda S, Gorman AM, Hori O, Samali A (2010) Cellular stress responses: Cell survival and cell death. Int J Cell Biol 2010: 214074. https://doi.org/10.1155/2010/214074

Gani BA, Alghassani AQ, Mubarak Z, Bachtiar EW, Bachtiar BM (2017a) Potential of cigarette smoke condensate to increase biofilm formation of Candida albicans isolate ATCC 10261). J Syiah Kuala Dent Soc 2: 33–39.

Gani BA, Bachtiar EW, Bachtiar BM (2017b) The role of cigarettes smoke condensate in enhanced Candida albicans virulence of salivary isolates based on time and temperature. J Int Dent Med Res 10: 769–777.

Gulati M, Nobile CJ (2016) Candida albicans biofilms: Development, regulation, and molecular mechanisms. Microbes Infect 18: 310–321. https://doi.org/10.1016/j.micinf.2016.01.002

He Y-H, Tian X-B, Wan H-C, Wen Y-L, Zhang F-F, Ma Q-R (2009) Study on protein extraction methods for Streptococcus mutans. Hua Xi Kou Qiang Yi Xue Za Zhi 27: 100–103.

Jabra-Rizk MA, Kong EF, Tsui C, Nguyen MH, Clancy CJ, Fidel PL, Noverr M (2016) Candida albicans pathogenesis: Fitting within the host-microbe damage response framework. Infect Immun 84: 2724–2739. https://doi.org/10.1128/iai.00469-16

LaDage LD (2015) Environmental change, the stress response, and neurogenesis. Integr Comp Biol 55: 372–383. https://doi.org/10.1093/icb/icv040

Li P, Seneviratne CJ, Alpi E, Vizcaino JA, Jin L (2015) Delicate metabolic control and coordinated stress response critically determine antifungal tolerance of Candida albicans biofilm persisters. Antimicrob Agents Chemother 59:6101–6112. https://doi.org/10.1128/aac.00543-15

Lim J, Ryu S, Kim JW, Kim WY (2018) Molecular generative model based on conditional variational autoencoder for de novo molecular design. J Cheminform 10: 31. https://doi.org/10.1186/s13321-018-0286-7

Lin HC, Kuo Y-L, Lee W-J, Yap H-Y, Wang S-H (2016) Antidermatophytic activity of ethanolic extract from Croton tiglium. BioMed Res Int 2016: 3237586. https://doi.org/10.1155/2016/3237586

Mishra R, Panda AK, De Mandal S, Shakeel M, Bisht SS, Khan J (2020) Natural anti-biofilm agents: Strategies to control biofilm-forming pathogens. Front Microbiol 11: 566325. https://doi.org/10.3389/fmicb.2020.566325

Nobile CJ, Schneider HA, Nett JE, Sheppard DC, Filler SG, Andes DR, Mitchell AP (2008) Complementary adhesin function in C. albicans biofilm formation. Curr Biol 18: 1017–1024. https://doi.org/10.1016/j.cub.2008.06.034

Parente-Rocha JA, Bailão AM, Amaral AC, Taborda CP, Paccez JD, Borges CL, Pereira M (2017) Antifungal resistance, metabolic routes as drug targets, and new antifungal agents: an overview about endemic dimorphic fungi. Med Inflamm 2017: 9870679. https://doi.org/10.1155/2017/9870679

Pinto CE, Farias DF, Carvalho AF, Oliveira JT, Pereira ML, Grangeiro TB, Freire JE, Viana DA, Vasconcelos IM (2015) Food safety assessment of an antifungal protein from Moringa oleifera seeds in an agricultural biotechnology perspective. Food Chem Toxicol 83: 1–9. https://doi.org/10.1016/j.fct.2015.05.012

Ponde NO, Lortal L, Ramage G, Naglik JR, Richardson JP (2021) Candida albicans biofilms and polymicrobial interactions. Crit Rev Microbiol 47: 91–111. https://doi.org/10.1080/1040841X.2020.1843400

Prasanna S, Doerksen R (2009) Topological polar surface area: A useful descriptor in 2D-QSAR. Curr Med Chem 16: 21–41. https://doi.org/10.2174/092986709787002817

Qwele K, Hugo A, Oyedemi S, Moyo B, Masika P, Muchenje V (2013) Chemical composition, fatty acid content and antioxidant potential of meat from goats supplemented with moringa (Moringa oleifera) leaves, sunflower cake and grass hay. Meat Science 93: 455–462. https://doi.org/10.1016/j.meatsci.2012.11.009

Rock KL, Kono H (2008) The inflammatory response to cell death. Annu Rev Pathol 3: 99–126. https://doi.org/10.1146/annurev.pathmechdis.3.121806.151456

Ruta LL and Farcasanu IC (2021) Coffee and yeasts: From flavor to biotechnology. Fermentation 7: 9. https://doi.org/10.3390/fermentation7010009

Santos LMM, Silva PM, Moura MC, Carvalho Junior AR, Amorim PK, Procópio TF, Coelho L, Silva LCN, Paiva PMG, Santos NDL and Napoleão TH (2021) Anti-Candida activity of the water-soluble lectin from Moringa oleifera seeds (WSMoL). J Mycol Med 31: 101074. https://doi.org/10.1016/j.mycmed.2020.101074

Senthilkumar S, Sivakumar T, Arulmozhi K and Mythili N (2015) Gas chromatography-mass spectroscopy evaluation of bioactive phytochemicals of commercial green teas (Camellia sinensis) of India. Asian J Pharm Clin Res 8: 278–282.

Singh A, Verma R, Murari A, Agrawal A (2014) Oral candidiasis: An overview. J Oral Maxillofac Pathol 18: 81–85. https://doi.org/10.4103/0973-029X.141325

Soraya C, Alibasyah ZM, Gani, BA (2021) Biomass index and viscosity values of Moringa oleifera influenced by Enterococcus faecalis. J Syiah Kuala Dent Soc 6: 1–5. https://doi.org/10.24815/jds.v6i1.21885

Soraya C, Syafriza D, Gani BA (2022) Antibacterial effect of Moringa oleifera gel to prevent the growth, biofilm formation, and cytotoxicity of Streptococcus mutans. J Int Dent Med Res 15: 1053–1061.

Sutton S (2011) Measurement of microbial cells by optical density. J Valid Technol 17: 46–49.

Syafriza D, Sutadi H, Primasari A and Siregar Y (2021) Spectrophotometric analysis of Streptococcus mutans growth and biofilm formation in saliva and histatin-5 relate to pH and viscosity. Pesqui Bras Odontopediatria Clin Integr 21: e0018. https://doi.org/10.1590/pboci.2021.004

Tits J, Cammue BPA, Thevissen K (2020) Combination therapy to treat fungal biofilm-based infections. Int J Mol Sci 21: 8873. https://doi.org/10.3390/ijms21228873

Unuofin JO, Lebelo SL (2020) Antioxidant effects and mechanisms of medicinal plants and their bioactive compounds for the prevention and treatment of type 2 diabetes: An updated review. Oxid Med Cell Longev 2020: 1356893. https://doi.org/10.1155/2020/1356893

Van De Waterbeemd H, Gifford E (2003) ADMET in silico modelling: towards prediction paradise? NatRev Drug Discov 2: 192–204. https://doi.org/10.1038/nrd1032

Yusuf H, Husna F, Gani BA (2021) The chemical composition of the ethanolic extract from Chromolaena odorata leaves correlates with the cytotoxicity exhibited against colorectal and breast cancer cell lines. J Pharm Pharmacogn Res 9: 344–356. https://doi.org/10.56499/jppres20.969_9.3.344

Zarnowiec P, Lechowicz L, Czerwonka G, Kaca W (2015) Fourier transform infrared spectroscopy (FTIR) as a tool for the identification and differentiation of pathogenic bacteria. Curr Med Chem 22: 1710–1718.https://doi.org/10.2174/0929867322666150311152800

© 2023 Journal of Pharmacy & Pharmacognosy Research

Parámetros farmacocinéticos en el salón de clases

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 160-178, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1472_11.1.160

Expert Opinion

Conceptos y aplicaciones de los parámetros farmacocinéticos: Una guía para el salón de clases

[Concepts and applications of pharmacokinetic parameters: A guide for the classroom]

Jorge Duconge-Soler1*, Víctor Mangas Sanjuan2, Gledys Reynaldo Fernández3

1Departamento de Ciencias Farmacéuticas, Escuela de Farmacia, Universidad de Puerto Rico, PO Box 365067, 00936-5067, San Juan, Puerto Rico.

2Departamento de Farmacia, Tecnología Farmacéutica y Parasitología, Facultad de Farmacia, Universidad de Valencia, 46100 Burjassot, Valencia, España.

3Departamento de Farmacia, Instituto de Farmacia y Alimentos, Universidad de La Habana, Calle 222 y 23 Ave. La Coronela, La Lisa, 13600, Habana, Cuba.

*E-mail: jorge.duconge@upr.edu

Abstract

Context: Pharmacokinetic studies play a fundamental role in making informed decisions during the drug development stage and fulfilling regulatory agencies’ requirements for drug approval. Disposition profiles of plasma drug concentrations over time can be characterized by using non-compartmental analysis, compartmental and physiological-based modeling. These models allow us to determine the pharmacokinetic parameters that best describe the absorption, distribution, metabolism, and excretion (ADME) processes.

Aims: To develop a conceptual and practical guide for the classroom on the most relevant pharmacokinetic parameters and their applications.

Results: The apparent volume of distribution (Vd), systemic drug clearance (CL), bioavailability (F) and elimination half-life (t1/2) are among the most relevant pharmacokinetic parameters discussed in this article. The Vd describes the relationship at equilibrium between the amount of drug in the body and its plasma concentrations after distribution, used to calculate the initial dose to reach the target drug concentration. The CL describes the relationship between plasma drug concentrations and the rate of elimination from the body, allowing calculation of a maintenance dosing rate to maintain an average target concentration at steady-state. The t1/2 is the time required to halve the plasma drug concentration, whereas F is critical to understand the biological performance of the drug formulation.

Conclusions: In this teacher’s topic text, we emphasize the importance of these parameters for optimizing strategies of model-informed dose individualization. Indeed, they are crucial for predicting systemic drug exposures and how long the drug will last in the body, as well as time to steady state after multiple-dosing regimens.

Keywords: bioavailability; clearance; elimination half-life; pharmacokinetic parameters; volume of distribution.

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Resumen

Contexto: Los estudios farmacocinéticos juegan un papel fundamental en la toma de decisiones informadas durante la etapa de desarrollo de fármacos y para su aprobación final por las agencias reguladoras. Los perfiles de disposición sistémica del fármaco se caracterizan mediante análisis no-compartimental, modelos compartimental y de base fisiológica, permitiendo determinar los parámetros farmacocinéticos que describen la absorción, distribución, metabolismo y excreción (ADME).

Objetivos: Desarrollar una guía conceptual y práctica para el salón de clases sobre los parámetros farmacocinéticos más relevantes y sus aplicaciones.

Resultados: El volumen aparente de distribución (Vd), el aclaramiento sistémico (CL), la biodisponibilidad (F) y el tiempo de vida media de eliminación (t1/2) están entre los parámetros farmacocinéticos más relevantes discutidos en este artículo. El Vd describe la relación entre la cantidad de fármaco en el cuerpo y sus concentraciones plasmáticas post-equilibrio distributivo y se utiliza para calcular la dosis inicial. El CL describe la relación entre las concentraciones plasmáticas del fármaco y su velocidad de eliminación, lo que permite calcular la dosis para mantener la concentración deseada. El t1/2 es el tiempo necesario para reducir a la mitad su concentración plasmática, mientras que F es fundamental para comprender el rendimiento biológico de la formulación.

Conclusiones: En este texto educativo, enfatizamos la importancia de estos parámetros para optimizar las estrategias de individualización de dosis asistida por modelación. Estos parámetros son fundamentales para predecir la exposición sistémica al fármaco y cuánto este durará en el cuerpo, así como el tiempo requerido para alcanzar el estado estacionario después de múltiples dosis.

Palabras Clave: aclaramiento; biodisponibilidad; parámetros farmacocinéticos; tiempo de vida media de eliminación; volumen de distribución.

jppres_pdf_free

Citation Format: Duconge Soler J, Mangas Sanjuan V, Reynaldo Fernández G (2023) Conceptos y aplicaciones de los parámetros farmacocinéticos: Una guía para el salón de clases [Concepts and applications of pharmacokinetic parameters: A guide for the classroom]. J Pharm Pharmacogn Res 11(1): 160–178. https://doi.org/10.56499/jppres22.1472_11.1.160
References

Amidon GL, Lennernäs H, Shah VP, Crison JR (1995) A theoretical basis for a biopharmaceutics drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 12: 413–420. https://doi.org/10.1023/A:1016212804288

Atkinson AJ Jr., Ruo TI, Frederiksen MC (1991) Physiological basis of multicompartmental models of drug distribution. Trends Pharmacol Sci 12(3): 96–101. https://doi.org/10.1016/0165-6147(91)90515-t

Benet LZ (2013) The role of BCS (biopharmaceutics classification system) and BDDCS (biopharmaceutics drug disposition classification system) in drug development. J Pharm Sci 102(1): 34–42. https://doi.org/10.1002/jps.23359

Brown J, Brown K, Forrest A (2012) Vancomycin AUC24/MIC ratio in patients with complicated bacteremia and infective endocarditis due to methicillin-resistant Staphylococcus aureus and its association with attributable mortality during hospitalization. Antimicrob Agents Chemother 56(2): 634–638. https://doi.org/10.1128/AAC.05609-11

Chen ML, Shah V, Patnaik R, Adams W, Hussain A, Conner D, Mehta M, Malinowski H, Lazor J, Huang SM, Hare D, Lesko L, Sporn D, Williams R (2001) Bioavailability and bioequivalence: An FDA regulatory overview. Pharm Res 18: 1645–1650. https://doi.org/10.1023/a:1013319408893

Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16: 31–41. https://doi.org/10.1159/000180580

Duconge J (2008) Applying organ clearance concepts in a clinical setting. Am J Pharm Edu 72(5): 121. https://doi.org/10.5688/aj7205121

FDA – Food and Drug Administration (1977) 42 FR 1648, Federal Register Volume 42, Issue 5, January 7, 1977, as amended at 63 FR 64222 – Bioavailability and Bioequivalence Requirements; Abbreviated Applications; Proposed Revisions. Available at https://www.govinfo.gov/content/pkg/FR-1998-11-19/pdf/98-30880.pdf [Accessed on December 8, 2021].

Katzung BG (2018) Basic & Clinical Pharmacology. 14th ed. LANGETM Medical Books/McGraw-Hill Education Co. Inc. Medical Publishing Division.

Loo JC, Riegelman S (1968) New method for calculating the intrinsic absorption rate of drugs. J Pharm Sci 57(6): 918–928. https://doi.org/10.1002/jps.2600570602

Macheras P (1987) Method of residuals: estimation of absorption and elimination rate constants having comparable values. Biopharm Drug Dispos 8(1): 47–56. https://doi.org/10.1002/bdd.2510080106

Nemeroff CB (2003) Improving antidepressant adherence. J Clin Psychiatry 64(Suppl 18):25-30. PMID: 14700452.

Perucca E (2006) Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol 61(3): 246–255. https://doi.org/10.1111/j.1365-2125.2005.02529.x

Rosenbaum S (2011) Basic pharmacokinetics and pharmacodynamics: An integrated textbook and computer simulations. Hoboken, New Jersey: John Wiley & Sons, Inc.

Rowland M, Tozer TN (2011) Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications. 4th ed. Wolters Kluwer/Lippincott Williams & Wilkin, pp. 839.

Rybak MJ, Le J, Lodise TP, Levine DP, Bradley JS, Liu C, Mueller BA, Pai MP, Wong-Beringer A, Rotschafer JC, Rodvold KA, Maples HD, Lomaestro B (2020a) Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Clin Infect Dis 71(6): 1361–1364. https://doi.org/10.1093/cid/ciaa303

Rybak MJ, Le J, Lodise TP, Levine DP, Bradley JS, Liu C, Mueller BA, Pai MP, Wong-Beringer A, Rotschafer JC, Rodvold KA, Maples HD, Lomaestro BM (2020b) Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 77(11): 835–864. https://doi.org/10.1093/ajhp/zxaa036

Shargel L, Wu-Pong, S, Yu ABC (2005a) Biopharmaceutic Considerations in Drug Product Design, Chapter 14, In: Applied Biopharmaceutics and Pharmacokinetics. 5th edition. New York, NY: McGraw-Hill, p. 446–447.

Shargel L, Wu-Pong, S, Yu ABC (2005b) Physiologic Drug Distribution and Protein Binding, Chapter 10, In: Applied Biopharmaceutics and Pharmacokinetics. 5th edition. New York, NY: McGraw-Hill, p. 252.

Shargel L, Yu ABC (2015a) Pharmacokinetics of Oral Absorption, Chapter 7, In: Applied Biopharmaceutics and Pharmacokinetics. 7th ed., New York, NY: McGraw-Hill, pp. 168–170.

Shargel L, Yu ABC (2015b) Physiologic Pharmacokinetic Models, Mean Residence Time and Statistical Moment Theory, Chapter 22, In: Applied Biopharmaceutics and Pharmacokinetics. 7th edition. New York, NY: McGraw-Hill, pp. 731–751.

Wagner JG, Nelson E (1963) Percent absorbed time plots derived from blood level and/or urinary excretion data. J Pharm Sci 52:610–611.

Wagner JG (1975) Application of the Loo-Riegelman absorption method. J Pharmacokinet Biopharm 3(1): 51–67. https://doi.org/10.1007/BF01066595

Wagner JG (1974) Application of the Wagner-Nelson absorption method to the two-compartment open model. J Pharmacokinet Biopharm 2(6): 469-486. https://doi.org/10.1007/BF01070942

Wilkinson GR, Shand DG (1975) A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 18: 377–390. https://doi.org/10.1002/cpt1975184377

© 2023 Journal of Pharmacy & Pharmacognosy Research

Ethnobotanical study in Fez-Meknes region of Morocco

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 137-159, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1459_11.1.137

Original Article

Ethnobotanical study of medicinal plants in the Fez-Meknes region of Morocco

[Estudio etnobotánico de plantas medicinales en la región de Fez-Meknes de Marruecos]

Sara Tlemcani1*, Amal Lahkimi2, Noureddine Eloutassi2, Ahmed Bendaoud2, Anouar Hmamou2, Hicham Bekkari1

1Laboratory of Biotechnology, Conservation and Valorization of Natural Phytoresources, Faculty of Sciences, University Sidi Mohamed Ben Abdellah, Fez, Morocco.

2Laboratory of Molecular Organometallic Materials Engineering and Environment, Faculty of Sciences, University Sidi Mohamed Ben Abdellah, Fez, Morocco.

*E-mail: sara.tlemcani@usmba.ac.ma

Abstract

Context: The region of Fez-Meknes has a wide variety of aromatic and medicinal plants that can be explored in different ways to draw their virtues and overcome human health problems.

Aims: To identify ethnobotanically the main medicinal plants and collect data about their uses in the region of Fez.

Methods: During each interview, both the personal information and the plants used were collected. The questionnaire revealed the use frequency of each part of the plants (VPP). It also sheds light on the importance of each species (RFC). Furthermore, it showed the relative importance of the families and the method of preparation (FIV).

Results: The results disclosed the richness of the region in terms of medicinal plants. A total of 57 species were identified and grouped into 24 families. The most abundant families were Lamiaceae (FIV = 5.461), Compositae (FIV= 6.085), and Apiaceae (FIV = 6.307). The most cited species were Plantago major L. (RFC = 27.3%), Olea europaea L. (RFC = 31.3 %), and Daphne gnidium L. (RFC = 32.6%). The leaves are the most plant part used (VPP = 0.416). The most used preparation method was decoction (32%). The most declared pathologies were digestive (16%), dermatological (15%), and respiratory affections (13%).

Conclusions: The ethnobotanical study showed the region’s floristic richness and allowed the identification of the different plants involved in many recipes to overcome human health problems

Keywords: aromatic and medicinal plants; ethnobotanical study; Fez-Meknes region; natural remedies.

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Resumen

Contexto: La región de Fez-Meknes cuenta con una gran variedad de plantas aromáticas y medicinales que se pueden explorar de diferentes formas para aprovechar sus virtudes y superar los problemas de salud humana.

Objetivos: Identificar etnobotánicamente las principales plantas medicinales y recoger datos sobre sus usos en la región de Fez.

Métodos: Durante cada entrevista se recogió tanto la información personal como las plantas utilizadas. El cuestionario reveló la frecuencia de uso de cada parte de las plantas (VPP), también arrojó luz sobre la importancia de cada especie (RFC). Además, mostró la importancia relativa de las familias y el método de preparación (FIV).

Resultados: : Los resultados dieron a conocer la riqueza de la región en cuanto a plantas medicinales, se identificaron un total de 57 especies, agrupadas en 24 familias. Las familias más abundantes fueron Lamiaceae (FIV = 5,461), Compositae (FIV = 6,085), luego Apiaceae (FIV = 6,307). Las especies más citadas fueron Plantago major L. (RFC = 27,3%), Olea europaea L. (RFC = 31,3%) y Daphne gnidium L. (RFC= 32,6%). Las hojas fueron la parte de la planta más utilizada (VPP = 0,416). El método de preparación más utilizado fue la decocción (32%). Las patologías más declaradas fueron afecciones digestivas (16%), dermatológicas (15%) y respiratorias (13%).

Conclusiones: El estudio etnobotánico mostró la riqueza florística de la región y también permitió identificar las diferentes plantas involucradas en multitud de recetas para superar los problemas de salud humana.

Palabras Clave: estudio etnobotánico; Región de Fez-Meknes; plantas aromáticas y medicinales; remedios naturales.

jppres_pdf_free

Citation Format: Tlemcani S, Lahkimi A, Eloutassi N, Bendaoud A, Hmamou A, Bekkari H (2023) Ethnobotanical study of medicinal plants in the Fez-Meknes region of Morocco. J Pharm Pharmacogn Res 1(1): 137–159. https://doi.org/10.56499/jppres22.1459_11.1.137
References

Achour S, Chebaibi M, Essabouri H, Bourhia M, Ouahmane L, Salamatullah M, Aboul-Soud M, Giesy JP (2022) Ethnobotanical study of medicinal plants used as therapeutic agents to manage diseases of humans. Evid Based Complement Alternat Med 2022: 4104772. https://doi.org/10.1155/2022/4104772

Alami M, Kharchoufa L, Bencheikh N, Elachouri M (2021) Ethnobotanical profile of medicinal plants used by people of North-eastern Morocco: Cross-cultural and Historical approach (Part I). Ethnobot Res Appl 21: 34. http://dx.doi.org/10.32859/era.21.34.1-45

Ammor K, Mahjoubi F, Bousta, D, Chaqroune A (2020) Ethnopharmacological survey of medicinal plants used in the traditional treatment of kidney stones realized in Fez-Morocco. Ethnobot Res Appl 19: 50. http://dx.doi.org/10.32859/era.19.50.1-12

Barkaoui M, Katiri A, Boubaker H, Msanda F (2017) Ethnobotanical survey of medicinal plants used in the traditional treatment of diabetes in ChtoukaAitBaha and Tiznit (Western Anti-Atlas), Morocco. J Ethnopharmacol 198: 338-350. https://doi.org/10.1016/j.jep.2017.01.023

Belhaj S, Dahmani J, Belahbib N, Zidane L (2020) Ethnopharmacological and ethnobotanical study of medicinal plants in the Central High Atlas, Morocco. Ethnobot Res Appl 20: 18. http://dx.doi.org/10.32859/era.20.18.1-40

Bellakhdar J (1997) La Pharmacopée Marocaine Traditionnelle: Médecine Arabe Et Savoirs Populaires. Editions Le Fennec, Casablanca/Ibis Press, Paris, 764 p.

Benkhnigue O, Zidane L, Fadli M, Elyacoubi H, Rochdi A, Douira A (2010) Ethnobotanical study of medicinal plants in the Mechraâ Bel Ksiri region of Morocco. Acta Bot Barc 53: 191-216.

Benlamdini N, Elhafian M, Rochdi A, Zidane L (2014) Etude floristique et ethnobotanique de la flore médicinale du Haut Atlas oriental (Haute Moulouya). J Appl Biosci 78(1):6771-6787.  https://doi.org/10.4314/jab.v78i1.17

Bouayyadi L, El Hafian M, Zidane L (2015) Etude floristique et ethnobotanique de la flore médicinale dans la région du Gharb, Maroc. J Appl Biosci 93: 8770-8788. https://doi.org/10.4314/jab.v93i1.10

Boutabia L, Telailia S, Menaa M (2020) Traditional therapeutic uses of Marrubium vulgare L. by local populations in the Haddadaregion (Souk Ahras, Algeria). Ethnobot Res Appl 19: 44. http://dx.doi.org/10.32859/era.19.44.1-11

Bouyahya A, Abrini J, Et-Touys A, Bakri Y, Dakka N (2017) Indigenous knowledge of the use of medicinal plants in the North-West of Morocco and their biological activities. Eur J Integr Med 13: 9-25. https://doi.org/10.1016/j.eujim.2017.06.004

Chebat A, Skalli S, Errihani H, Boulaâmane L, Mokrim M, Mahfoud T, Soulaymani R, Kahouadji A (2014) Étude de prévalence des effets indésirables liés à l’utilisation des plantes médicinales par les patients de l’Institut National d’Oncologie, Rabat. Phytothérapie 12(1): 25-32. https://doi.org/10.1007/s10298- 013-0828-4

Eddouks M, Ajebli M, Hebi M (2017) Ethnopharmacological survey of medicinal plants used in Daraa-Tafilalet region (Province of Errachidia) Morocco. J Ethnopharmacol 198: 516-530. https://doi.org/10.1016/j.jep.2016.12.017

El Hachlafi N, Chebat A, Bencheikh RS, Fikri Benbrahim K (2020) Ethnopharmacological study of medicinal plants used for chronic diseases treatment in Rabat-Sale-Kenitra Region (Morocco). Ethnobot Res Appl 20: 2. http://dx.doi.org/10.32859/era.20.2.1-23

El Hassani M, Douiri EM, Bammi J, Zidane L, Badoc A, Douira A (2013) Plantes Médicinales de La Moyenne Moulouya (Nord-Est Du Maroc). Ethnopharmacologia 50: 39-53

El Hilah F, Bengueddour R, Rochdi A, Lahcen Z (2016) Étude ethnobotanique des plantes médicinales utilisées dans le traitement des affections dermatologiques dans le plateau central marocain. J Appl Biosci 98: 9252–9260. https://doi.org/10.4314/jab.v98i1.2

El Khomsi M, Dandani Y, Chaachouay N, Hmouni D (2022) Ethnobotanical study of plants used for medicinal, cosmetic, and food. J Pharm Pharmacogn Res 10(1): 13-29. https://doi.org/10.56499/jppres21.1084_10.1.13

El Rhaffari L, Zaid A (2002) Pratique de la phytothérapie dans le sud-est du Maroc (Tafilalet): un savoir empirique pour une pharmacopée rénovée. In: Fleurentin J. (ed.), Pelt J.M. (ed.), Mazars G. (ed.), Lejosne J.C. (trad.), Cabalion Pierre (collab.). Des sources du savoir aux médicaments du futur: actes du 4e congrès européen d’ethnopharmacologie = From the sources of knowledge to the medicines of the future = proceedings of the 4th European Congress on Ethnopharmocology. Paris (FRA); Metz: IRD; SFE, p. 293-318. Congrès Européen d’Ethnopharmacologie, 4., Metz (FRA).

El Yahyaoui O, Ouaaziz NA, Sammama A, Kerrouri S, Bouabid B, Lrhorfi LA, Bengueddour, R (2015) Ethnobotanical study: Medicinal plants commercialized in the province of Laayoune; identification and use. Int J Innov Appl Stud 12(3): 533-541.

El-Assri E, ElBarnossi A, Chebaibi M, Hmamou A, El Asmi H, Bouia A, Eloutassi N (2021) Ethnobotanical survey of medicinal plants in Taounate, Pre-Rif of Morocco. Ethnobot Res Appl 22: 36. http://dx.doi.org/10.32859/era.22.36.1-23

El-Hilaly J, Hmammouchi M, Lyoussi B (2003) Ethnobotanical studies and economic evaluation of medicinal plants in Taounate Province (Northern Morocco). J Ethnopharmacol 86(2- 3): 149-158. https://doi.org/10.1016/S0378-8741(03)00012-6

Es-Safi I, Mechchate H, Amaghnouje A, Jawhari F, Bari A, Cerruti PF, Avella M, Grafov A, Bousta D (2020) Medicinal plants used to treat acute digestive system problems in the region of Fez-Meknes in Morocco: An ethnopharmacological survey. Ethnobot Res Appl 20: 25. http://dx.doi.org/10.32859/era.20.25.1-14

Fadil M, Farah A, Haloui T, Rachiq S (2015) Étude ethnobotanique des plantes exploitées par les coopératives et les associations de la région Meknès-Tafilalet au Maroc. Phytothérapie 13(1): 19- 30. https://doi.org/10.1007/s10298-014-0902-2

Ghourri M, Zidane L, Douira A (2013) Catalogue of medicinal plants used in the treatment of renal lithiasis in the province of Tan-Tan (Saharan Morocco). International J Biol Chem Sci 7(4): 1688-1700. https://doi.org/10.15171/jrip.2016.27

Gomez-Beloz A (2002) Plant use knowledge of the Winikina Warao: The case for questionnaires in ethnobotany. Econ Bot 56(3): 231-241. https://doi.org/10.1663/0013-0001(2002)056[0231:PUKOTW]2.0.CO;2

Hachi M, Hachi T, Belahbib N, Dahmani J, Zidane L (2015) Contribution to the study and floristic ethnobotany flora medicinal use at the city of Khenifra (Morocco)[France]. Int J Innov Appl Stud 11(3): 754-770.

Jaadan H, Akodad M, Moumen A, Baghour M, Skalli A, Ezrari S, Belmalha S (2020) Ethnobotanical survey of medicinal plants growing in the region of “Oulad Daoud Zkhanine” (Nador Province), in Northeastern Morocco. Ethnobot Res Appl 19: 39. https://doi.org/10.32859/era.19.39.1-12

Jdaidi N, Hasnaoui B (2016) Etude floristique et éthnobotanique des plantes médicinales au nordouest de la Tunisie: cas de la communauté d’Ouled Sedra. J Adv Res Sci Technol 3(1): 281-291.

Jeddi M, BenzianeOuaritini Z, Fikri-Benbrahim K (2021) Ethnobotanical study of medicinal plants in northern Morocco (Taounate): Case of Mernissa. Ethnobot Res Appl 21: 35. http://dx.doi.org/10.32859/era.21.35.1-23

Khabbach A, Libiad M, Ennabili A, Bousta D (2012) Medicinal and cosmetic use of plants from the province of Taza, Northern Morocco. Bol Latinoam Caribe Plant Med Aromat 11(1): 46-60.

Labiad H, Et-Tahir A, Ghanmi M, Satrani B, Aljaiyash A, Chaouch A, Fadli M (2020) Ethnopharmacological survey of aromatic and medicinal plants of the pharmacopoeia of northern Morocco. Ethnobot Res Appl 19: 45. http://dx.doi.org/10.32859/era.19.45.1-16

Lahsissene H, Kahouadji A, Hseini S (2009) Catalogue des plantes médicinales utilisées dans la région de Zaër (Maroc Occidental). Lejeunia 186.

Mechchate H, Es-Safi I, Zahra Jawhari F, Bari A, Grafov A, Bousta D (2020) Ethnobotanical survey about the management of diabetes with medicinal plants used by diabetic patient in Region of Fez-Meknes, Morocco. Ethnobot Res Appl 19: 12. http://dx.doi.org/10.32859/era.19.12.1-28

Mehdioui R, Kahouadji A (2007) Etude ethnobotanique auprès de la population riveraine de la forêt d’Amsittène: cas de la Commune d’Imi n’Tlit (Province d’Essaouira). Bull Inst Scie Rabat, section Sciences de la Vie 29: 11-20.

Neffati M, Sghaier M (2014) Développement et valorisation des plantes aromatiques et médicinales (PAM) au niveau des zones désertiques de la région MENA (Algérie, Egypte, Jordanie, Maroc et Tunisie) Rapport principal du Projet MENA-DELP: Partage des connaissances et de coordination sur les écosystèmes désertiques et les moyens de subsistance au profit de l’Algérie, l’Egypte, la Jordanie, le Maroc et la Tunisie : 143 p

Orch H, Douira A, Zidane L (2015) Étude ethnobotanique des plantes médicinales utilisées dans le traitement du diabète, et des maladies cardiaques dans la région d’Izarène (Nord du Maroc). J Appl Biosci 86(1): 7940. https://doi.org/10.4314/jab.v86i1.3

Saibari Z, Iraque W, Mohti H, EL Rhaffari L, Zaid A (2021) Study on herb-drug associations, case of the Fez-Meknes region. International Congress on Health Vigilance, Kenitra, Morocco. E3S Web Conf 319: 1004. https://doi.org/10.1051/e3sconf/202131901004

Salhi S, Fadli M, Zidane L, Douira A (2010) Etudes floristique et ethnobotanique des plantes médicinales de la ville de Kénitra (Maroc). Lazaroa 31: 133-146.

Scherer AM, Motti R, Weckeerie CS (2005) Traditional plant use in the areas of Monte Vesole and Ascea, Cilento National Park (Campania, Southern Italy). J Ethnopharmacol 97: 129-143. https://doi.org/10.1016/j.jep.2004.11.002

Sghaier M, Gammoudi T (2007) Le secteur des Plantes Aromatiques et Médicinales (PAM) en Tunisie: importance et opportunités socio-économiques. Rev Régs Arid 2(numéro special): 834-852.

Slimani I, Najem M, Belaidi R, Bachiri L, Bouiamrine E, Nassiri L (2016) Étude ethnobotanique des plantes médicinales utilisées dans la région de Zerhoun. Int J Innov Appl Stud 15: 846-863.

Sreekeesoon DP, Mahomoodally MF (2014) Ethnopharmacological analysis of medicinal plants and animals used in the treatment and management of pain in Mauritius. J Ethnopharmacol 157:181-200. https://doi.org/10.1016/j.jep.2014.09.030

Tahraoui A, El-Hilaly J, Israili ZH, Lyoussi B (2007) Ethnobotanical survey of plants used in the traditional treatment of hypertension and diabetes in southeastern Morocco (Errachidia province). J Ethnopharmacol 110: 105-117. https://doi.org/10.1016/j.jep.2006.09.011

Tahri N, El-Basti A, Zidane L, Rochdi A, Douira A (2012) Ethnobotanical study of medicinal plants in the province of Settat (Morocco). Kastamonu Univ Orman Fak Derg 12(2): 192-208.

Tardío J, Pardo de Santayana M (2008) Cultural Importance Indices: A Comparative analysis based on the useful wild plants of Southern Cantabria (Northern Spain). Econ Bota 62(1): 24-39. https://doi.org/10.1007/s12231-007-9004-5

© 2023 Journal of Pharmacy & Pharmacognosy Research

Metabolites and anticholinesterase activity of A. suberitoides

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 129-136, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1511_11.1.129

Original Article

Metabolite profile and in vitro cholinesterase inhibitory activity of extract and fractions of Aaptos suberitoides

[Perfil de metabolitos y actividad inhibidora de la colinesterasa in vitro del extracto y fracciones de Aaptos suberitoides]

Hanifa R. Putri1, Rhesi Kristiana2, I Wayan Mudianta3, Edwin Setiawan4, Aty Widyawaruyanti5,6, Nitra Nuengchamnong7, Nungruthai Suphrom8, Suciati Suciati5,6*

1Master Program in Pharmaceutical Sciences, Faculty of Pharmacy Universitas Airlangga, Surabaya 60115, East Java, Indonesia.

2Indonesian Marine Education & Research Organisation (MERO) Foundation, Desa Tulamben, Karangasem 80853, Bali, Indonesia.

3Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Pendidikan Ganesha, Singaraja 81116, Bali, Indonesia.

4Department of Biology, Faculty of Science and Data Analytics, Institut Teknologi Sepuluh Nopember, Surabaya 60115, East Java, Indonesia.

5Department of Pharmaceutical Sciences, Faculty of Pharmacy Universitas Airlangga, Surabaya 60115, East Java, Indonesia.

6Center for Natural Product Medicine Research and Development, Institute of Tropical Diseases, Universitas Airlangga, Surabaya 60115, East Java, Indonesia.

7Science Laboratory Center, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand.

8Department of Chemistry, Faculty of Science and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand.

*E-mail: suciati@ff.unair.ac.id

Abstract

Context: Marine sources such as sponges have shown a significant impact on the drug development from nature. Metabolites isolated from sponges show diversity in terms of structural features and pharmacological properties. Several sponges have been reported to have potency as cholinesterase inhibitors as one of the target therapies for Alzheimer’s disease.

Aims: To investigate the potency of marine sponge Aaptos suberitoides as cholinesterase inhibitors and to explore the chemistry of the sponge.

Methods: The cholinesterase inhibitory assay was carried out against two enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), based on the modified Ellman’s method. The chemistry of the active fractions was studied by LC-MS/MS method, followed by molecular networking using GNPS.

Results: The results suggested that the extract and fractions inhibited both AChE and BChE enzymes. All samples demonstrated more potent inhibition against AChE compared to BChE enzymes. The n-hexane fraction gave the strongest inhibition against both AChE and BChE, with IC50 values of 4.76 µg/mL and 6.79 µg/mL, respectively. Based on the LC-MS/MS analysis, alkaloids were detected in the n-hexane and ethyl acetate fractions. Four alkaloids were identified in the ethyl acetate fraction, namely demethylaaptamine, aaptamine, isoaaptamine, and 8,9,9-trimethoxy-9H-benzo[de][1,6]naphthyridine at RT 1.52, 1.67, 2.92, and 3.22 mins, respectively. Aaptamine was also identified in the n-hexane fraction together with demethyloxyaaptamine.

Conclusions: The extract, n-hexane, and ethyl acetate fractions of A. suberitoides have shown promising cholinesterase inhibitory properties against both AChE and BChE enzymes. The alkaloids present in the active fractions may be responsible for the bioactivity.

Keywords: Aaptos suberitoides; alkaloid; Alzheimer’s disease; cholinesterase inhibitor.

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Resumen

Contexto: Las fuentes marinas como las esponjas han mostrado un impacto significativo en el desarrollo de fármacos a partir de la naturaleza. Los metabolitos aislados a partir de esponjas muestran diversidad en cuanto a características estructurales y propiedades farmacológicas. Se ha informado que varias esponjas tienen potencia como inhibidores de la colinesterasa como una de las terapias diana para la enfermedad de Alzheimer.

Objetivos: Investigar la potencia de la esponja marina Aaptos suberitoides como inhibidor de la colinesterasa y explorar la química de la esponja.

Métodos: El ensayo de inhibición de la colinesterasa se llevó a cabo contra dos enzimas, la acetilcolinesterasa (AChE) y la butirilcolinesterasa (BChE), basándose en el método de Ellman modificado. La química de las fracciones activas se estudió por el método LC-MS/MS, seguido de la creación de redes moleculares mediante GNPS.

Resultados: Los resultados sugirieron que el extracto y las fracciones inhibían las enzimas AChE y BChE. Todas las muestras demostraron una inhibición más potente contra las enzimas AChE en comparación con las BChE. La fracción de n-hexano produjo la mayor inhibición tanto contra la AChE como contra la BChE, con valores de IC50 de 4,76 µg/mL y 6,79 µg/mL, respectivamente. Según el análisis LC-MS/MS, se detectaron alcaloides en las fracciones de n-hexano y acetato de etilo. Se identificaron cuatro alcaloides en la fracción de acetato de etilo, a saber, desmetilaaptamina, aaptamina, isoaaptamina y 8,9,9-trimetoxi-9H-benzo[de][1,6]naftiridina a RT 1,52; 1,67; 2,92 y 3,22 minutos, respectivamente. También se identificó aaptamina en la fracción n-hexano junto con desmetiloxiaaptamina.

Conclusiones: Las fracciones de extracto, n-hexano y acetato de etilo de A. suberitoides han mostrado prometedoras propiedades inhibidoras de la colinesterasa frente a las enzimas AChE y BChE. Los alcaloides presentes en las fracciones activas pueden ser los responsables de la bioactividad.

Palabras Clave: Aaptos suberitoides; alcaloide; enfermedad de Alzheimer; inhibidor de la colinesterasa.

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Citation Format: Cane HPCA, Putri HR, Kristiana R, Mudianta IW, Setiawan E, Widyawaruyanti A, Nuengchamnong N, Suphrom N, Suciati S (2023) Metabolite profile and in vitro cholinesterase inhibitory activity of extract and fractions of Aaptos suberitoides. J Pharm Pharmacogn Res 11(1): 129–136. https://doi.org/10.56499/jppres22.1511_11.1.129
References

Alonso D, Castro A, Martinez A (2005) Marine compounds for the therapeutic treatment of neurological disorders. Expert Opin Ther Patents15(10): 137-1386. https://doi.org/10.1517/13543776.15.10.1377

Aristyawan AA, Setyaningtyas VF, Wahyuni TS, Widyawaruyanti A, Ingkaninan K, Suciati S (2022) In vitro acetylcholinesterase inhibitory activities of fractions and iso-agelasine C isolated from the marine sponge Agelas nakamurai. J Res Pharm 26(2): 279-286. http://dx.doi.org/10.29228/jrp.126

Bharate SB, Manda S, Joshi P, Singh B, Vishwakarma RA (2012) Total synthesis and anti-cholinesterase activity of marine-derived bis-indole alkaloid fascaplysin. MedChemComm 3: 1098–1103 https://doi.org/10.1039/C2MD20076G

Botić T, Defant A, Zanini P, Žužek MC, Frangež R, Janussen D, Kersken D, Knez Ž, Mancini I, Sepčić K (2017) Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors. Eur J Med Chem 136: 294-304. https://doi.org/10.1016/j.ejmech.2017.05.019

Dalai MK, Bhadra S, Chaudhary SK, Bandyopadhyay A, Mukherjee PK (2014) Anti-cholinesterase activity of the standardized extract of Syzygium aromaticum L. Pharmacogn Mag 10(Suppl 2): S276-82. https://doi.org/10.4103/0973-1296.133275

de Voogd NJ, Alvarez B, Boury-Esnault N, Carballo JL, Cárdenas P, Díaz MC, Dohrmann M, Downey R, Hajdu E, Hooper JNA, Kelly M, Klautau M, Manconi R, Morrow CC, Pisera AB, Ríos P, Rützler K, Schönberg C, Vacelet J, van Soest RWM (2023) World Porifera Database. Accessed at https://www.marinespecies.org/porifera on 2022-10-01. https://doi.org/10.14284/359

Dos Santos TC, Gomes TM, Pinto BAS, Camara AL, De Andrade Paes AM (2018) Naturally occurring acetylcholinesterase inhibitors and their potential use for Alzheimer’s disease therapy. Front Pharmacol 9: 1192. https://doi.org/10.3389/fphar.2018.01192

Ellman GL, Courtney KD, Andres V Jr, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7: 88-95. https://doi.org/10.1016/0006-2952(61)90145-9

Erdogan-Orhan I, Ozcelik B, Konuklugil B, Putz A, Kaban UG, Proksch P (2012) Bioactivity screening of the selected Turkish marine sponges and three compounds from Agelas oroides. Rec Nat Prod 6(4): 356-367.

Hafez Ghoran S, Kijjoa A (2021) Marine-derived compounds with anti-Alzheimer’s disease activities. Mar Drugs 19: 410. https://doi.org/10.3390/md19080410

He Q, Miao S, Ni N, Man Y, Gong K (2020) A Review of the secondary metabolites from the marine sponges of the Genus Aaptos. Nat Prod Commun 15(9). https://doi.org/10.1177/1934578X20951439

Kubota T, Ishiguro Y, Yamamoto S, Fromont J, Kobayashi JI (2010) Platisidines A-C, N-methylpyridinium alkaloids from an Okinawan marine sponge of Plakortis species. Heterocycles 80(2): 1407-1412. https://doi.org/10.3987/COM-09-S(S)131

Langjae R, Bussarawit S, Yuenyongsawad S, Ingkaninan K, Plubrukarn A (2007) Acetylcholinesterase-inhibiting steroidal alkaloid from the sponge Corticium sp. Steroids 72(9-10): 682–685. https://doi.org/10.1016/j.steroids.2007.05.005

Lima E, Medeiros J (2022) Marine organisms as alkaloid biosynthesizers of potential anti-Alzheimer agents. Mar Drugs 20(1): 75. https://doi.org/10.3390/md20010075

Moodie LWK, Sepčić K, Turk T, Frangež R, Svenson J (2019) Natural cholinesterase inhibitors from marine organisms. Nat Prod Rep 36: 1053-1092. https://doi.org/10.1039/C9NP00010K

Ng YP, Or TCT, Ip NY (2015) Plant alkaloids as drug leads for Alzheimer’s disease. Neurochem Int 89: 260-270. https://doi.org/10.1016/j.neuint.2015.07.018

Nothias LF, Petras D, Schmid R, Dührkop K, Rainer J, Sarvepalli A, et al. (2020) Feature-based molecular networking in the GNPS analysis environment. Nat Methods 17(9): 905-908. https://doi.org/10.1038/s41592-020-0933-6

Nukoolkarn VS, Saen-oon S, Rungrotmongkol T, Hannongbua S, Ingkaninan K, Suwanborirux K (2008) Petrosamine, a potent anticholinesterase pyridoacridine alkaloid from a Thai marine sponge Petrosia n. sp. Bioorg. Med. Chem16(13): 6560–6567. https://doi.org/10.1016/j.bmc.2008.05.027

Silva M, Seijas P, Otero P (2021) Exploitation of marine molecules to manage Alzheimer’s disease. Mar Drugs. 19: 373. https://doi.org/10.3390/md19070373

Sirimangkalakitti N, Olatunji OJ, Changwichit K, Saesong T, Chamni S, Chanvorachote P, Ingkaninan K, Plubrukarn A, Suwanborirux K (2015) Bromotyrosine alkaloids with acetylcholinesterase inhibitory activity from the Thai sponge Acanthodendrilla sp. Nat Prod Commun 10: 1945-1949.

Suciati, Rabgay K, Fachrunniza Y, Saesong T, Hadi TA, Wahyuni TS, Widyawaruyanti A, Ingkaninan K (2019) Enzyme inhibitory activities of marine sponges against cholinesterase and 5-reductase. Malays Appl Biol 48(3): 77-83.

Tamfu AN, Kucukaydin S, Yeskaliyeva B, Ozturk M, Dinica RM (2021) Non-alkaloid cholinesterase inhibitory compounds from natural sources. Molecules 26(18): 5582. https://doi.org/10.3390/molecules26185582

Turk T, Frangež R, Sepčić K (2007) Mechanisms of toxicity of 3-alkylpyridinium polymers from marine sponge Reniera sarai. Mar Drugs 5(4): 157-167.

Voskressensky LG, Kovaleva SA, Borisova TN, Eresko AB, Tolkunov VS, Listratova AV, de Candia M, Altomare C, Varlamov AV (2013) Recyclization of benzofuropyridines by the action of activated alkynes in the synthesis of spiro[benzofuropyridines], representatives of a new class of acetylcholinesterase inhibitors. Chem Heterocycl Comp 49: 930–940. https://doi.org/10.1007/s10593-013-1328-8

Wang M, Carver JJ, Phelan VV, Sanchez LM, Garg N, Peng Y, Nguyen DD, et al. (2016) Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nat Biotechnol 34(8):828-837. https://doi.org/10.1038/nbt.3597

Wu T, Salim AA, Bernhardt PV, Capon RJ (2021) Amaurones A-K: Polyketides from the fish gut-derived fungus Amauroascus sp. CMB-F713. J Nat Prod 84(2): 474-482. https://doi.org/10.1021/acs.jnatprod.0c01343

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