Tag Archives: flavonoids

Photoprotective compounds from Baccharis papillosa

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 33-46, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1477_11.1.33

Original Article

Quantification and in vitro photo-protective studies of phenolic compounds from Baccharis papillosa Rusby

[Cuantificación y estudios de fotoprotección in vitro de compuestos fenólicos de Baccharis papillosa Rusby]

Alberto Calle1#, Cecilia K. Curi-Borda1#, Cervando Gutiérrez1,2, Lily Salcedo1, Yonny Flores1, Giovanna R. Almanza1*

1Laboratorio de Bioorgánica, Instituto de Investigaciones Químicas (IIQ), Facultad de Ciencias Puras y Naturales, Universidad Mayor de San Andrés, Calle Andrés Bello y Calle 27 Cota Cota, Edificio FCPN, 4º Piso, La Paz- Bolivia.

2Instituto de Investigaciones Fármaco Bioquímicas (IIFB), Facultad de Ciencias Farmaceúticas y Bioquímicas, Universidad Mayor de San Andrés, Av. Saavedra 222, Miraflores, La Paz-Bolivia.

#Authors contributed equally to the present study.

*E-mail: galmanza@fcpn.edu.bo

Abstract

Context: The ethanolic extract of the leaves from Baccharis papillosa, a plant used in Bolivian folk medicine, presents high UVB/UVA absorption spectrum, and therefore, it could have photo-protective potential.

Aims: To isolate, identify and quantify the compounds of an enriched extract in phenolic compounds obtained from the ethanolic extract of Baccharis papillosa in different seasons and geographical altitudes, and evaluate its photo-protective potential.

Methods: The enriched extract in phenolic compounds was submitted to phytochemical analysis for compound isolation. The enriched extract and isolated compounds were identified by NMR, and monitored by HPLC and spectroscopic methods. The enriched extract with photo-protective potential was analyzed to determine its Spectroscopic Sun Protection Factor (SSPF), its Broad Spectrum Index (BSI) and its photo-protective activity on Escherichia coli bacteria.

Results: Six flavonoids and two cinnamic acid derivatives were isolated and identified. Four of them are reported in B. papillosa for the first time in this study. The highest concentration of total flavonoids was observed in spring and at the highest altitude. The major compound, drupanin, was the main responsible of the high UVB (290-320 nm) absorption spectrum. The high presence of flavonoids in the extract explains the absorption spectrum in the UVA (320-400 nm) region.

Conclusions: The phenolic compounds enriched extract has photo-protective properties comparable to standard commercial synthetic sunscreens and presents an attractive BSI.

Keywords: Broad Spectrum Index (BSI); cinnamic acid derivative; flavonoids; photo-protective activity; Spectroscopic Sun Protection Factor (SSPF).

Resumen

Contexto: El extracto etanólico de las hojas de Baccharis papillosa, planta utilizada en la medicina popular boliviana, presenta un alto espectro de absorción UVB/UVA por lo que podría presentar potencial fotoprotector.

Objetivos: Aislar, identificar y cuantificar los compuestos de un extracto enriquecido en compuestos fenólicos obtenido a partir del extracto etanólico de Baccharis papillosa en diferentes épocas del año y altitudes geográficas y evaluar su potencial fotoprotector.

Métodos: El extracto enriquecido en compuestos fenólicos fue sometido a análisis fitoquímicos para aislamiento de compuestos. El extracto enriquecido y los compuestos aislados fueron identificados por RMN, y monitoreados por HPLC y métodos espectroscópicos. El potencial fotoprotector del extracto enriquecido se analizó mediante la determinación de su Factor de Protección Solar Espectroscópico (SSPF), su Índice de Amplio Espectro (BSR) y su actividad fotoprotectora sobre bacterias Escherichia coli.

Resultados: Se aislaron e identificaron seis flavonoides y dos derivados del ácido cinámico, de los cuales, cuatro de ellos se reportan en este estudio por primera vez en esta especie. La mayor concentración de flavonoides totales se observó en primavera y a mayor altura. El compuesto mayoritario, drupanina, fue el principal responsable del alto espectro de absorción UVB (290-320 nm) del extracto enriquecido. La alta presencia de flavonoides en el extracto explica el espectro de absorción en la región UVA (320-400 nm).

Conclusiones: El extracto enriquecido en compuestos fenólicos tiene propiedades fotoprotectoras comparables a filtros solares sintéticos comerciales estándar y presenta un amplio espectro de protección solar.

Palabras Clave: derivado del ácido cinámico; factor de protección solar espectroscópico; flavonoides; fotoprotección; índice de amplio espectro.

Citation Format: Calle A, Curi-Borda CK, Gutierrez C, Salcedo L, Flores Y, Almanza GR (2023) Quantification and in vitro photo-protective studies of phenolic compounds from Baccharis papillosa Rusby. J Pharm Pharmacogn Res 11(1): 33–46. https://doi.org/10.56499/jppres22.1477_11.1.33
References

Almanza G, Arduz C, Balderrama L, Ocaña L, Flores E (2000) Estudio fitoquímico de Baccharis leptophylla, biodirigido contra Neurospora crassa. Rev Bol Quim 17: 1-8.

Almeida WA, d. S. Sousa LRD, dos Santos A, de Azevedo AS, do Nascimento AM, Amparo TR, Bianco de Souza GH, Henrique dos Santos OD, Leão Andrade  Â, Cazati T, de Abreu Vieira PM, Pires Bueno PC, Rebello dos Santos VM (2020) Green propolis: In vitro photoprotective and photostability studies of single and incorporated extracts in a sunscreen formulation. Rev Bras Farmacogn 30: 436-443. https://doi.org/10.1007/s43450-020-00071-z

Andersen OM, Markham KR (2005) Flavonoids: Chemistry, biochemistry and applications: CRC Press, pp. 1256.

Calderón H (2001) Fotoprotección, bases y aplicación. Rev Chil Reumatol 17: 54-58.

Calle A, San Martín Á, Melgarejo M, Flores Y, Almanza G (2017) Evaluation of flavonoid contents and antibacterial activity of five Bolivian Baccharis species. Rev Bol Quím 34: 112-122.

Calle A, Yupanqui J, Flores Y, Almanza GR (2012) Flavonoides de Baccharis boliviensis. Rev Bol Quím 29: 158-163.

Camacho F (2001) Antiguos y nuevos aspectos de la fotoprotección. Rev Int Dermatol Dermocosmét Clín 4: 441-448.

CAS Common Chemistry (2021) CAS, a division of the American Chemical Society, n.d. Quercetin 3,4′-dimethyl ether. Retrieved from https://commonchemistry.cas.org/detail?cas_rn=33429-83-3 [Consulted July, 2022]

Catalogue No. TM50-TM60 (2002) McFarland Standard, for in vitro use only. Dalynn, Biologicals. http://www.dalynn.com/dyn/ck_assets/files/tech/TM53.pdf [Consulted July, 2022]

ChemSpider CSID:600426 (2021) trans-caffeic acid. Retrieved from http://www.chemspider.com/Chemical-Structure.600426.html [Consulted July, 2022]

Cornard J-P, Lapouge C (2006) Absorption spectra of caffeic acid, caffeate and their 1: 1 complex with Al (III): density functional theory and time-dependent density functional theory investigations. J Phys Chem 110: 7159-7166. https://doi.org/10.1021/jp060147y

da Silva Fernandes A, Alencar AS, Evangelista H, Mazzei JL, Felzenszwalb I (2015) Photoprotective and toxicological activities of extracts from the Antarctic moss Sanionia uncinata. Pharmacogn Mag 11: 38-43. https://doi.org/10.4103/0973-1296.149701

da Silva VV, Ropke CD, de Almeida RL, Miranda DV, Kera CZ, Rivelli DP, Sawada TCH, Barros SBM (2005) Chemical stability and SPF determination of Pothomorphe umbellata extract gel and photostability of 4-nerolidylcathecol. Int J Pharm 303: 125-131. https://doi.org/10.1016/j.ijpharm.2005.07.006

Diffey BL (1994) A method for broad spectrum classification of sunscreens. Int J Cosmet Sci 16: 47-52. https://doi.org/10.1111/j.1467-2494.1994.tb00082.x

Enríquez S, Quispe RE, Amurrio P, Peñaranda JC, Calle A, Orsag V, Almanza GR (2018) Flavonoid contents in leaves of Baccharis latifolia, according to the type of leaf, and its dependence on the physicochemical properties of soils. Rev Bol Quím 35: 146-154.

Escobar Z, Flores Y, Tejeda L, Alvarado JA, Sterner O, Almanza GR (2009) Phenolic compounds from Baccharis papillosa subsp. papillosa. Rev Bol Quím 26: 111-117.

Fleming DP (2008) Quantification of the environmental solar ultraviolet radiation field at the human eye and the investigation of peripherally focused rays. (Ph.D. thesis) Technological University Dublin, Dublin, Ireland. https://doi.org/10.21427/D7XG6P

Gajardo S, Aguilar M, Stowhas T, Salas F, Lopez J, Quispe C, Buc-Calderon P, Benites J (2016) Determination of sun protection factor and antioxidant properties of six Chilean Altiplano plants. Bol Latinoam Caribe Plant Med Aromat15: 352-363.

Garcia Forero A, Villamizar Mantilla DA, Núñez LA, Ocazionez RE, Stashenko EE, Fuentes JL (2019) Photoprotective and antigenotoxic effects of the flavonoids apigenin, naringenin and pinocembrin. Photochem Photobiol 95: 1010-1018. https://doi.org/10.1111/php.13085

Gene RM, Cartañá C, Adzet T, Marin E, Parella T, Canigueral S (1996) Anti-inflammatory and analgesic activity of Baccharis trimera: Identification of its active constituents. Planta Med 62: 232-235. https://doi.org/10.1055/s-2006-957866

Grotewold E (2006) The science of flavonoids. Columbus, Ohio: Springer. https://doi.org/10.1007/978-0-387-28822-2

Körner C (2007) The use of ‘altitude’ in ecological research. Trends Ecol Evol 22: 569-574. https://doi.org/10.1016/j.tree.2007.09.006

Landry LG, Chapple CC, Last RL (1995) Arabidopsis mutants lacking phenolic sunscreens exhibit enhanced ultraviolet-B injury and oxidative damage. Plant Physiol 109: 1159-1166. https://doi.org/10.1104/pp.109.4.1159

Lavola A (1998) Accumulation of flavonoids and related compounds in birch induced by UV-B irradiance. Tree Physiol 18: 53-58. https://doi.org/10.1093/treephys/18.1.53

Li J, Ou-Lee T-M, Raba R, Amundson RG, Last RL (1993) Arabidopsis flavonoid mutants are hypersensitive to UV-B irradiation. Plant Cell 5: 171-179. https://doi.org/10.1105/tpc.5.2.171

Lim H, Draelos Z (2009) Clinical guide to sunscreens and photoprotection. New York: Informa Healthcare USA, pp. 320.

Loza Almanza R, Neri Guarachi L, López Gavincha Y, Mamani Mamani M, Arias Miranda JL, Almanza Vega G, Gonzales Dávalos E, Bermejo Benito P (2011) Evaluación de la toxicidad de los extractos etanólicos de Baccharis latifolia y Baccharis papillosa en animales de experimentación. Biofarbo 19: 22-27.

Mansur J, Rodrigues M, D’ascenção M, Azulay R (1986a) Correlação entre a determinação do fator de proteção solar em seres humanos e por espectrofotometria. An Bras Dermatol 61(4): 167-172.

Mansur J, Rodrigues M, D’ascenção M, Azulay R (1986b) Determinação do fator de proteção solar por espectrofotometria. An Bras Dermatol 61(3): 121-124.

Mazza CA, Zavala J, Scopel, AL, Ballaré CL (1999) Perception of solar UVB radiation by phytophagous insects: behavioral responses and ecosystem implications. Proc Natl Acad Sci USA 96: 980-985. https://doi.org/10.1073/pnas.96.3.980

Monschein M, Jaindl K, Buzimkić S, Bucar F (2015) Content of phenolic compounds in wild populations of Epilobium angustifolium growing at different altitudes. Pharm Biol 53: 1576-1582. https://doi.org/10.3109/13880209.2014.993039

Moreno MI, Moreno LH (2010) Fotoprotección. Rev Asoc Colomb Dermatol 18: 31-39.

Muela A, Garcia-Bringas J, Arana I, Barcina I (2000) The effect of simulated solar radiation on Escherichia coli: the relative roles of UV-B, UV-A, and photosynthetically active radiation. Microb Ecol 39: 65-71. https://doi.org/10.1007/s002489900181

Nichols JA, Katiyar SK (2010) Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res 302: 71-83. https://doi.org/10.1007/s00403-009-1001-3

Nole G, Johnson AW (2004) An analysis of cumulative lifetime solar ultraviolet radiation exposure and the benefits of daily sun protection. Dermatol Ther 17: 57-62. https://doi.org/10.1111/j.1396-0296.2004.04S1007.x

Peñaranda JC, Rodrigo G, Ticona-Bustillos A, Valenzuela E, Ramos S, San Martin A, Ghezzi F, Almanza GR (2020) Variation in concentration of flavonoids and chlorophyll, and changes on morphology and foliar anatomy, due to visible (PAR) or ultraviolet (UVA, UVB) radiation in Baccharis latifolia. Rev Bol Quim 37: 210-222. http://doi.org/10.34098/2078-3949.37.5.1

Pérez MT (2012) Fotoprotección: 15 consejos para un broceado seguro. Farm Prof 26: 46-50.

Rengifo-Penadillos R (2013) Cuantificación de flavonoides en el extracto etanólico de propóleos. Pharmaciencia 1: 51-56.

Ribeiro RP (2004) Desenvolvimento e validação da metodologia de análise do teor de filtros solares e determinação do FPS in vitro em formulações fotoprotetoras comerciais. PhD Thesis, UFRJ, Rio de Janeiro, Brasil.

Rigel DS, Berson DS, Ceilley RI, Cole CA, Draelos ZD (2006) Photoprotection: Recent advances in sunscreen stability. Skin and Allergy News (suppl.): 4-11.

Rodrigo GC, Almanza GR, Akesson B, Duan R-D (2010) Antiproliferative activity of extracts of some Bolivian medicinal plants. J Med Plant Res 4: 2204-2210.

Salcedo Ortiz L, Flores Y, Sterner O, Almanza Vega GR (2013) ent-kaurane diterpenoids from Baccharis leptophylla Rev Bol de Quím 30: 60-65.

Sánchez-Saldaña L, Lanchipa P, Pancorbo J, Regis A, Sánchez E (2002) Fotoprotectores tópicos. Dermatol Peru 12(2): 156-163.

Silva-Carvalho R, Baltazar F, Almeida-Aguiar C (2015) Propolis: A complex natural product with a plethora of biological activities that can be explored for drug development. Evid Based Complement Alternat Med 2015: 206439. https://doi.org/10.1155/2015/206439

Sotillo WS, Tarqui S, Huang X, Almanza G, Oredsson S (2021) Breast cancer cell line toxicity of a flavonoid isolated from Baccharis densiflora. BMC Complement Med Ther 21: 188. https://doi.org/10.1186/s12906-021-03349-4

Talhaoui N, Gómez-Caravaca AM, León L, De la Rosa R, Segura-Carretero A, Fernández-Gutiérrez A (2014) Determination of phenolic compounds of ‘Sikitita’olive leaves by HPLC-DAD-TOF-MS. Comparison with its parents ‘Arbequina’and ‘Picual’olive leaves. LWT- Food Sci Technol 58: 28-34. https://doi.org/10.1016/j.lwt.2014.03.014

Tarqui  S, Flores Y, Almanza  GR (2012) Polyoxygenated flavonoids from Baccharis pentlandii. Rev Bol Quím 29: 10-14.

Villagómez JR, Mollinedo P, Almanza GR (2006) (E)-3-prenil-4-hidroxicinamato de metilo de Baccharis santelices Rev Bol Quím 23: 13-18.

Zaratti F, Forno R, Cuarita L, Saavedra P (2003) Seis años de medidas de ozono y radiación ultravioleta en La Paz, Bolivia. Rev Bol Fis 9: 48-51.

Zdero C, Bohlmann F, Solomon J, King R, Robinson H (1989) Ent-clerodanes and other constituents from bolivian Baccharis species. Phytochemistry 28: 531-542. https://doi.org/10.1016/0031-9422(89)80047-0

© 2023 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Virtual screening of lead flavonoids against DENV2

J. Pharm. Pharmacogn. Res., vol. 10, no. 4, pp. 660-675, July-August 2022.

DOI: https://doi.org/10.56499/jppres22.1375_10.4.660

Original Article

Flavonoids as potential inhibitors of dengue virus 2 (DENV2) envelope protein

[Flavonoides como posibles inhibidores de la proteína de la cubierta del virus del dengue 2 (DENV2)]

Rachel Raditya Renantha1, Alvin Richardo Liga1, Christy Bianca Tanugroho1, Lovine Xaviera Denovian1, Siti Lateefa Az Zahra Budiyanto2, Arli Aditya Parikesit2*

1Department of Biomedicine, School of Life Sciences, Indonesia International Institute for Life Sciences, Jl. Pulomas Barat Kav.88 Jakarta 13210 Indonesia.

2Department of Bioinformatics, School of Life Sciences, Indonesia International Institute for Life Sciences, Jl. Pulomas Barat Kav.88 Jakarta 13210 Indonesia.

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

Abstract

Context: Dengue viruses (DENVs) are the cause of dengue disease, which is one of the most frequent diseases caused by mosquito-borne viral infections. Currently, no specific treatment is available for dengue.

Aims: To identify the most promising inhibitors of dengue virus 2 (DENV2) envelope protein of DENV2 envelope protein from flavonoids compounds through computational methods.

Methods: Structures of 54 flavonoids were collected, then the compounds were screened based on Lipinski’s rules, and there were only 34 compounds that passed the screening. Then QSAR analysis was performed, followed by molecular docking analysis, ADMET evaluation, and molecular dynamics simulations to assess the stability of the protein.

Results: Based on the QSAR analysis, only 32 compounds were subjected to molecular docking analysis. Silymarin had the highest docking score, while juglanin had the lowest ACE score compared to positive controls. The ADMET evaluation showed silymarin and juglanin had good absorption and could not penetrate the blood-brain barrier. In contrast to silymarin which had negative results for the Ames test, carcinogenicity, skin sensitization, and eye irritation, juglanin was positive for Ames test and skin sensitization. Even though the molecular dynamic simulation of both ligands with DENV2 envelope protein showed unstable confirmation, it did not necessarily mean that the ligands cannot be used as inhibitors since the molecular docking results provide evidence of the ligands binding to the DENV2 envelope protein.

Conclusions: Based on the favorable results of QSAR analysis, molecular docking, and ADMET evaluation, juglanin and silymarin were chosen as the candidate with the most potential for DENV2 envelope protein inhibitors. However, further analyses such as in vitro and in vivo analyses are necessary to validate the result of this study.

Keywords: DENV-2; envelope protein; flavonoids; molecular docking; virtual screening.

Resumen

Contexto: Los virus del dengue (DENV) son los causantes de la enfermedad del dengue, que es una de las enfermedades más frecuentes causada por infecciones virales transmitidas por mosquitos. Actualmente, no se dispone de un tratamiento específico para el dengue.

Objetivos: Identificar los inhibidores más prometedores de la proteína de la envoltura del virus del dengue 2 (DENV2) de la proteína de la envoltura del DENV2 a partir de compuestos de flavonoides a través de métodos computacionales.

Métodos: Las estructuras de 54 flavonoides fueron recolectadas. Los compuestos se seleccionaron según las reglas de Lipinski y solo 34 compuestos pasaron la selección. Luego se realizó el análisis QSAR, seguido de análisis de acoplamiento molecular, evaluación ADMET y simulaciones de dinámica molecular para evaluar la estabilidad de la proteína.

Resultados: Según el análisis QSAR, solo 32 compuestos se sometieron a análisis de acoplamiento molecular. La silimarina obtuvo la puntuación de acoplamiento más alta, mientras que juglanina obtuvo la puntuación ACE más baja en comparación con los controles positivos. La evaluación ADMET mostró que la silimarina y la juglanina tenían una buena absorción y no podían penetrar la barrera hematoencefálica. En contraste con la silimarina que tuvo resultados negativos para la prueba de Ames, carcinogenicidad, sensibilización de la piel e irritación de los ojos, la juglanina fue positiva para la prueba de Ames y la sensibilización de la piel. Aunque la simulación de la dinámica molecular de ambos ligandos con la proteína de la cubierta de DENV2 mostró una confirmación inestable, no significa necesariamente que los ligandos no puedan usarse como inhibidores, ya que los resultados del acoplamiento molecular proporcionan evidencia de que los ligandos se unen a la proteína de la cubierta de DENV2.

Conclusiones: En base a los resultados favorables del análisis QSAR, el acoplamiento molecular y la evaluación ADMET, la juglanina y la silimarina fueron elegidas como las candidatas con mayor potencial para los inhibidores de la proteína de la envoltura de DENV2. Sin embargo, se necesitan más análisis, como análisis in vitro e in vivo, para validar el resultado de este estudio.

Palabras Clave: acoplamiento molecular; DENV-2; flavonoides; proteína de envoltura; proyección virtual.

This image has an empty alt attribute; its file name is jppres_pdf_free.png
Citation Format: Renantha RR, Liga AR, Tanugroho CB, Denovian LX, Budiyanto SLAZ, Parikesit AA (2022) Flavonoids as potential inhibitors of dengue virus 2 (DENV2) envelope protein. J Pharm Pharmacogn Res 10(4): 660–675. https://doi.org/10.56499/jppres22.1375_10.4.660
References

Badshah S, Faisal S, Muhammad A, Poulson B, Emwas A, Jaremko M (2021) Antiviral activities of flavonoids. Biomed Pharmacother 140(9): 111596.

Bekhit A, Bekhit A (2014) Natural antiviral compounds. Stud Nat Prod Chem 42(1): 195–228.

Boonyasuppayakorn S, Reichert E, Manzano M, Nagarajan K, Padmanabhan R (2014) Amodiaquine, an antimalarial drug, inhibits dengue virus type 2 replication and infectivity. Antivir Res 106(6): 125–134.

Dong ZW, Yuan YF (2018) Juglanin suppresses fibrosis and inflammation response caused by LPS in acute lung injury. Int J Mol Med 41(6): 3353–3365.

Duhovny D, Nussinov R, Wolfson H (2002) Efficient unbound docking of rigid molecules. Lect Notes Comput Sci 2452(1):185–200.

Filimonov D, Lagunin A, Gloriozova T, Rudik A, Druzhilovskii D, Pogodin P, Poroikov V (2014) Prediction of the biological activity spectra of organic compounds using the pass online web resource. Chem Heterocy Comp 50(3): 444–457.

Guan L, Yang H, Cai Y, Sun L, Di P, Li W, Liu G, Tang Y (2019) ADMET-score – a comprehensive scoring function for evaluation of chemical drug-likeness. Medchemcomm 10(1): 148–157.

Hanwell M, Curtis D, Lonie D, Vandermeersch T, Zurek E, Hutchison G (2012) Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform 4(1): 17.

Hengstler J, Oesch F (2001) Ames Test. Ency Gen 1(1): 51–54.

Ho L, Liu P, Wang C, Wu J (2007) The development of a drug discovery virtual screening application on Taiwan. Unigrid Adv Grid Perv Comp 2(3): 38–47.

Hollingsworth SA, Dror RO (2018) Molecular dynamics simulation for all. Neuron 99(6): 1129–1143.

Hou G, Zeng K, Lan H, Wang Q (2018) Juglanin ameliorates UVB‑induced skin carcinogenesis via anti‑inflammatory and proapoptotic effects in vivo and in vitro. Int J Mol Med 42(3): 41–52.

Ismail N, Jusoh S (2016) Molecular docking and molecular dynamics simulation studies to predict flavonoid binding on the surface of DENV2 E protein. Interdiscip Sci 9(4): 499–511.

Karim A, Riahi V, Mishra A, Newton M, Dehzangi A, Balle T, Sattar A (2021) Quantitative toxicity prediction via meta ensembling of multitask deep learning models. ACS Omega 6(18): 12306–12317.

Krug RM, Aramini JM (2009) Emerging antiviral targets for influenza A virus. Trends Pharm Sci 30(6): 269–277.

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

Lagunin A, Stepanchikova A, Filimonov D, Poroikov V (2000) PASS: prediction of activity spectra for biologically active substances. Bioinformatics 16(8): 747–748.

Loaiza-Cano V, Monsalve-Escudero L, Filho C, Martinez-Gutierrez M, Sousa D (2020) Antiviral role of phenolic compounds against dengue virus: A review. Biomolecules 11(1): 11.

Low Z, OuYong B, Hassandarvish P, Poh C, Ramanathan B (2021) Antiviral activity of silymarin and baicalein against dengue virus. Sci Rep 11(1): 21221.

Mangas-Sanjuan V, González-Alvarez M, Gonzalez-Alvarez I, Bermejo M (2010) Drug penetration across the blood–brain barrier: an overview. Ther Del 1(4): 535–562.

Modrow S, Falke D, Truyen U, Schätzl H (2013) Viruses with single-stranded, positive-sense RNA genomes. Mol Vir 9(12): 185–349.

Morris G, Lim-Wilby M (2008) Molecular docking. Met Mol Bio 443(8): 365–382.

Ninfali P, Antonelli A, Magnani M, Scarpa E (2020) Antiviral properties of flavonoids and delivery strategies. Nutrients 12(9): 2534.

Parikesit AA (2018) Introductory Chapter: The Contribution of Bioinformatics as Blueprint Lead for Drug Design. In Ivana Glavic (Ed.), Molecular Insight of Drug Design (p. 7). InTech.

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

Poh MK, Yip A, Zhang S, Priestle JP, Ma NL, Smit JM, Schul W (2009) A small molecule fusion inhibitor of dengue virus. Antivir Res 84(3): 260–266.

Qamar M, Ashfaq U, Tusleem K, Mumtaz A, Tariq Q, Goheer A, Ahmed B (2017) In-silico identification and evaluation of plant flavonoids as dengue NS2B/NS3 protease inhibitors using molecular docking and simulation approach. Pak J Pharm Sci 30(6): 2119–2137.

Rajapakse S, Rodrigo C, Rajapakse A (2012) Treatment of dengue fever. Infect Drug Resist 5(1): 103–112.

Schaefer T, Panda P, Wolford R (2021) Dengue Fever. Treasure Island (FL): StatPearls Publishing.

Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson H (2005) PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Res 33(7): 363–367.

Schwarz S, Sauter D, Wang K, Zhang R, Sun B, Karioti A, Bilia A R, Efferth T, Schwarz W (2014) Kaempferol derivatives as antiviral drugs against the 3a channel protein of coronavirus. Planta Med 80(2-3): 177–182.

Shiloputra AF, Parikesit AA, Darmawan JT, Pricillia V, Turista DDR, Ansori, ANM (2021) An overview of the curcumin-based and allicin bioactive compounds as potential treatment to SARS-CoV-2 with structural bioinformatics tools. J Tek Lab 10(2): 59–67.

Surai P (2015) Silymarin as a natural antioxidant: An overview of the current evidence and perspectives. Antioxidants 4(1): 204–247.

Tantawichien T, Thisayakorn U (2017) Dengue. Negl Trop Dis- South Asia 5(10): 329–348.

Tian W, Chen C, Lei X, Zhao J, Liang J (2018a) CASTp 3.0: computed atlas of surface topography of proteins. Nucleic Acids Res 46(1): 363–367.

Tian Y, Zhou Y, Takagi T, Kameoka M, Kawashita N (2018b) Dengue virus and its inhibitors: A brief review. Chem Pharm Bull (Tokyo) 66(3): 191–206.

Verma R, Jatav V, Sharma S (2015) Identification of inhibitors of dengue virus (DENV1, DENV2 and DENV3) NS2b/NS3 serine protease: A molecular docking and simulation approach. Asian J Pharm Clin Res 8(1): 287–292.

Vicente C, Herbinger K, Fröschl G, Malta Romano C, de Souza Areias Cabidelle A, Cerutti Junior C (2016) Serotype influences on dengue severity: a cross-sectional study on 485 confirmed dengue cases in Vitória, Brazil. BMC Infect Dis 16(1): 320.

Vora J, Patel S, Athar M, Sinha S, Chhabria MT, Jha PC, Shrivastava N (2019) Pharmacophore modeling, molecular docking and molecular dynamics simulation for screening and identifying anti-dengue phytocompounds. J Biomol Struct Dyn 38(6): 1726–1740.

Wang L, Song J, Liu A, Xiao B, Li S, Wen Z, Lu Y, Du G (2020) Research progress of the antiviral bioactivities of natural flavonoids. Nat Prod Bioprospect 10(5): 271–283.

Wang N, Huang C, Dong J, Yao Z, Zhu M, Deng Z (2017) Predicting human intestinal absorption with modified random forest approach: a comprehensive evaluation of molecular representation, unbalanced data, and applicability domain issues. RSC Adv 7(31): 19007–19018.

Weber C, Sliva K, von Rhein C, Kümmerer B, Schnierle B (2015) The green tea catechin, epigallocatechin gallate, inhibits chikungunya virus infection. Antiviral Res 113(1): 1–3.

Wessel M, Mente S (2001) Chapter 25. ADME by computer. Annu Rep Med Chem 36(1): 257–266.

WHO – World Health Organization (2009) Dengue Guidelines for Diagnosis, Treatment, Prevention and Control, pp. 10–11.

WHO – World Health Organization (2022) Dengue and severe dengue. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue [Consulted 24 February 2022].

Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C (2021) ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res 49(1): 5–14.

Yan A, Wang Z, Cai Z (2008) Prediction of human intestinal absorption by GA feature selection and support vector machine regression. Int J Mol Sci 9(10): 1961–1976.

Yennamalli R, Subbarao N, Kampmann T, McGeary R, Young P, Kobe, B (2009) Identification of novel target sites and an inhibitor of the dengue virus E protein. J Comput Aided Mol Des 23(6): 333–341.

Zandi K, Teoh BT, Sam SS, Wong PF, Mustafa M, AbuBakar S (2011) Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virol J 8(1): 560.

Zarei M, Abidin N, Auwal S, Chay S, Abdul Haiyee Z, Md Sikin A, Saar N (2019) Angiotensin converting enzyme (ACE)-peptide interactions: Inhibition kinetics, in silico molecular docking and stability study of three novel peptides generated from palm kernel cake proteins. Biomolecules 9(10): 569

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Cytoprotective activity of Adelia ricinella



J Pharm Pharmacogn Res 9(6): 892-904, 2021.

DOI: https://doi.org/10.56499/jppres21.1093_9.6.892

Original article

Cytoprotective activity of extracts from Adelia ricinella L. aerial parts

[Actividad citoprotectora de extractos de las partes aéreas de Adelia ricinella L.]

Clara A. Berenguer-Rivas1, Onel Fong Lores2, Julio C. Escalona-Arranz1, Jorge de la Vega-Acosta2, Diana J. Arro-Díaz2, Frenkel Guisado-Bourzac3, Gabriel Llauradó-Maury4, Humberto J. Morris-Quevedo4*

1Department of Pharmacy, Faculty of Natural and Exact Sciences, Universidad de Oriente, Santiago de Cuba 5, CP 90500, Cuba.

2 Center of Toxicology and Biomedicine (TOXIMED), Medical University of Santiago de Cuba, Santiago de Cuba 4, CP 90400, Cuba.

3Laboratory of Genetic and Applied Genomics. School of Marine Sciences. Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.

4Center of Studies for Industrial Biotechnology (CEBI), Universidad de Oriente, Santiago de Cuba 5, CP 90500, Cuba.

*E-mail: jquevedo@uo.edu.cu

Abstract

Context: Several factors can affect the erythrocyte cell membrane integrity targeting important hematological alterations that can be avoided by the cytoprotective effect offered by some plant extracts.

Aims: To evaluate the cytoprotective activity of Adelia ricinella L. extracts on red blood cells (RBCs) membrane after hypotonic and oxidative treatments.

Methods: Total phenols and flavonoid contents were spectrophotometrically determined in three extracts: AR1 (ethanol 95%), AR2 (ethanol 50%), and AR3 (aqueous extract). Luteolin and apigenin were quantified using HPLC-DAD techniques. Hypotonic erythrocyte membrane stabilizing activity of plant extracts, their antioxidant protective effect on H2O2-induced cell damage, and cytotoxicity on Vero cells were explored. Control cells were treated with sodium diclofenac or ascorbic acid.

Results: AR2 extract showed the highest values of total phenols/flavonoids, as well as, for luteolin and apigenin with 207.5 and 1.86 µg/mL respectively. The extracts did not exert spontaneous hemolysis following the INVITOX protocol, presumably by the protective effect of high flavonoid content. A concentration-dependent pattern was observed on the hypotonic erythrocyte membrane stabilizing assay, in which both ethanol extracts but mainly AR1 (IC50 = 16.46 µg/mL) showed a significant activity with lower IC50 values than diclofenac-control group. On the other hand, AR2 (IC50 = 17.49 µg/mL) displayed the most potent cytoprotective effect on RBCs after H2O2-induced cell damage. Adelia ricinella extracts were not cytotoxic to mammalian Vero cells (IC50 > 256 μg/mL).

Conclusions: The study suggests that Adelia ricinella extracts can promote erythrocyte cytoprotection by protecting both membrane layers, thus preventing potential hematological alterations induced by oxidizing damage and probably, in inflammation-related diseases.

Keywords: Adelia ricinella; antioxidant; cytoprotection; flavonoids; red blood cells.

This image has an empty alt attribute; its file name is jppres_pdf_free.png
Resumen

Contexto: Varios factores afectan la integridad de la membrana eritrocitiaria, provocando alteraciones hematológicas, que pueden evitarse mediante el efecto citoprotector de extractos vegetales.

Objetivos: Evaluar la actividad citoprotectora de extractos de Adelia ricinella L. sobre la membrana eritrocitaria luego de tratamientos hipotónicos y oxidativos.

Métodos: El contenido de fenoles y flavonoides totales se determinó espectrofotométricamente en tres extractos: AR1 (etanol 95%), AR2 (etanol 50%) y AR3 (acuoso); la luteolina y apigenina se estimaron mediante HPLC-DAD. Se evaluó el efecto estabilizador de los extractos en membranas sometidas a tratamiento hipotónico, la actividad antioxidante ante el daño inducido por H2O2, y la citotoxicidad en células Vero. El diclofenaco de sodio y el ácido ascórbico se emplearon como controles.

Resultados: AR2 mostró valores superiores de fenoles totales/flavonoides, y de luteolina y apigenina con 207,5 y 1,86 µg/mL, respectivamente. Los extractos no causaron hemólisis espontánea en el protocolo INVITOX, probablemente debido al efecto protector de los flavonoides. Se observó un comportamiento dependiente de la concentración en el ensayo de estabilización de la membrana en solución hipotónica, en el que ambos extractos etanólicos (principalmente AR1, IC50 = 16,46 µg/mL), evidenciaron una actividad significativa con valores de IC50 menores al control con diclofenaco. AR2 (IC50 = 17,49 µg/mL) mostró el efecto citoprotector más potente frente al daño inducido por H2O2. Los extractos no resultaron citotóxicos en células Vero (IC50 > 256 μg/mL).

Conclusiones: Los extractos de Adelia ricinella L. pueden promover la citoprotección eritrocitaria en ambas superficies, y así prevenir posibles alteraciones hematológicas inducidas por daño oxidativo y presumiblemente, por enfermedades inflamatorias.

Palabras Clave: Adelia ricinella; antioxidante; citoprotección; flavonoides; glóbulos rojos.

This image has an empty alt attribute; its file name is jppres_pdf_free.png
https://jppres.com/jppres/pdf/vol9/jppres21.1093_9.6.892.pdf
Citation Format: Berenguer CA, Fong O, Escalona JC, de la Vega J, Arro DJ, Guisado F, Llauradó G, Morris HJ (2021) Cytoprotective activity of extracts from Adelia ricinella L. aerial parts. J Pharm Pharmacogn Res 9(6): 892–904. DOI: https://doi.org/10.56499/jppres21.1093_9.6.892

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Myricitrin and frankincense against MCF-7 resistance to epirubicin

J Pharm Pharmacogn Res 9(4): 497-508, 2021.

DOI: https://doi.org/10.56499/jppres21.1031_9.4.497

Original article

Myricitrin from Physalis pubescens L. leaves and frankincense decrease resistance of MCF-7 cells and ameliorate efficacy of epirubicin

[La miricitrina de las hojas de Physalis pubescens L. y la resina frankincense disminuyen la resistencia de las células MCF-7 y mejoran la eficacia de la epirrubicina]

Suzy Abd El-Hakeem El-Sherbeni1*, Ghada Mohammad Al-Ashmawy2

1Pharmacognosy Department, Faculty of Pharmacy, Tanta University. El-Gharbia, Tanta 31527, Egypt.

2Biochemistry Department, Faculty of Pharmacy, Tanta University. El-Gharbia, Tanta 31527, Egypt.

*E-mail: suzy.elsherbini@pharm.tanta.edu.eg

Abstract

Context: It was found that flavonoids and frankincense exert anti-cancer effect through their antioxidant and anti-inflammatory activities.

Aims: To evaluate the cytotoxic effect against MCF-7 cells of flavonoids isolated from Physalis pubescens L., frankincense ethanol extract and the combined therapy with epirubicin to reduce the resistance and the side effects.

Methods: MTT assay against MCF-7 was carried out for rutin, quercitrin, myricitrin and frankincense. The compound or extract with the best anti-cancer effect was tested against WI-38 cells. 50% inhibitory concentration (IC50) of the different treatments and the combined therapy with epirubicin against MCF-7 was determined. Assessment the effect on expression of ABCB1, TGF-β1 and ATG7 genes was done by RT-qPCR.

Results: Isolation and identification of myricitrin from leaves of Physalis pubescens L. was carried out for the first time. IC50 (µg/mL) regarding MCF-7 cells was of epirubicin (0.8 ± 0.052), rutin (350.16 ± 1.241), quercitrin (259.6 ± 1.45), myricitrin (114.0 ± 0.517), frankincense ethanol extract (86.8 ± 0.91), combined epirubicin + myricitrin (EM) (0.37 ± 0.087), combined epirubicin + frankincense (EF) (0.50 ± 0.1732). The IC50 µg/mL regarding WI-38 cells was of epirubicin (1.26 ± 0.0057), myricitrin (462.0 ± 1.062) and frankincense (299.5 ± 1.32). All assays were done at 48 h time interval. Myricitrin and EM reduced ABCB1 expression and upregulated expression of TGF-β1 and ATG7 genes. Frankincense and EF downregulated expression of ABCB1, TGF-β1 and ATG7 genes.

Conclusions: Myricitrin and frankincense would be a promising adjuvant therapy to improve epirubicin anticancer activity with minimal adverse effect.

Keywords: ABCB1; ATG7; flavonoids; MTT assay; TGF-β1; WI-38.

This image has an empty alt attribute; its file name is jppres_pdf_free.png
Resumen

Contexto: Se encontró que los flavonoides y la resina frankincense ejercen un efecto anticancerígeno a través de sus actividades antioxidantes y antiinflamatorias.

Objetivos: Evaluar el efecto citotóxico frente a células MCF-7 de flavonoides aislados de Physalis pubescens L., extracto etanólico de resina frankincense y la terapia combinada con epirrubicina para reducir las resistencias y los efectos secundarios.

Métodos: Se realizó ensayo MTT contra MCF-7 para rutina, quercitrina, miricitrina e incienso. El compuesto o extracto con el mejor efecto anticancerígeno se probó contra células WI-38. Se determinó la concentración inhibidora del 50% (IC50) de diferentes tratamientos y la terapia combinada con epirubicina contra MCF-7. La evaluación del efecto sobre la expresión de los genes ABCB1, TGF-β1 y ATG7 se realizó mediante RT-qPCR.

Resultados: Se realizó por primera vez el aislamiento e identificación de miricitrina de hojas de Physalis pubescens L. La CI50 (µg/mL) con respecto a las células MCF-7 fue de epirrubicina (0,8 ± 0,052), rutina (350,16 ± 1,241), quercitrina (259,6 ± 1,45), miricitrina (114.0 ± 0,517), extracto de etanólico de resina frankincense (86,8 ± 0,910), epirrubicina combinada + miricitrina (EM) (0,37 ± 0,087), epirrubicina + incienso (EF) combinados (0,50 ± 0,1732). La IC50 (µg/mL) con respecto a las células WI-38 fue de epirrubicina (1,26 ± 0,0057), miricitrina (462,0 ± 1,062) extracto de resina frankincense (299,5 ± 1,32). Todos los ensayos se realizaron en un intervalo de tiempo de 48 h. Myricitrin y EM redujeron la expresión de ABCB1 y aumentaron la expresión de los genes TGF-β1 y ATG7. El incienso y la EF redujeron la expresión de los genes ABCB1, TGF-β1 y ATG7.

Conclusiones: La miricitrina y el extracto frankincense serían una terapia adyuvante prometedora para mejorar la actividad anticancerosa de la epirrubicina con un efecto adverso mínimo.

Palabras Clave: ABCB1; ATG7; ensayo MTT; flavonoides; TGF-β1; WI-38s.

This image has an empty alt attribute; its file name is jppres_pdf_free.png
https://jppres.com/jppres/pdf/vol9/jppres21.1031_9.4.497.pdf
Citation Format: El-Sherbeni SA, Al-Ashmawy GM (2021) Myricitrin from Physalis pubescens L. leaves and frankincense decrease resistance of MCF-7 cells and ameliorate efficacy of epirubicin. J Pharm Pharmacogn Res 9(4): 497–508. DOI: https://doi.org/10.56499/jppres21.1031_9.4.497

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)