Analysing potential phytoconstituents from Viscum album (Suvarnabandaaka) targeting RAAS-mediated hypertension and renal protection: An in-silico approach
DOI:
https://doi.org/10.65327/kidneys.v15i1.600Keywords:
Viscum album, Suvarnabandaaka, Hypertension, In-silico, Molecular docking, PhytoconstituentsAbstract
Background and Aim: Hypertension is a significant health issue in the world that demands that natural options to synthetic drugs should be explored because of their side effects. One of the key causes of chronic kidney disease (CKD) is hypertension, which mainly causes dysregulation of renal RAAS signalling and vascular injury. This paper examines the antihypertensive effects of Viscum album by using in-silico molecular docking.
Material and Methods: Phytoconstituents of Viscum album were identified using seven phytoconstituents based on the scores of their oral bioavailability and drug-likeness. AutoDock 4.5.6 molecular docking was done against the following key hypertensive targets: ACE, Angiotensin-II receptor, β-1 adrenergic receptor, and calcium channel. Biovia Discovery Studio was used to visualise the interactions. Result: The phytoconstituents had better binding affinities with the target proteins than the standard drugs. It was worth noting that Chlorogenic acid, Oleanolic acid and Betulinic acid displayed a high interaction with ACE as the binding energy of the substance was -11.90, -11.84 and -11.65 kcal/mol, which exceeded that of Captopril of -5.89 kcal/mol. In the case of the Angiotensin-II receptor, Oleanolic acid, Chlorogenic acid, and Syringin demonstrated binding energies of -11.66, -10.67 and -10.05 kcal/mol, outperforming losartan’s -9.21 kcal/mol. Syringin, Chlorogenic acid, and Quercetin exhibited robust binding with the β-1 adrenergic receptor, with energies of -13.82, 13.59, and -12.05 kcal/mol, respectively, compared to Propranolol’s -7.48 kcal/mol. Additionally,
Chlorogenic acid, Oleanolic acid, and Quercetin interacted strongly with the calcium channel, with binding energies of -7.24, -7.06, and -7.00 kcal/mol, respectively, exceeding amlodipine’s -4.59 kcal/mol.
Conclusion: Such results indicate that Viscum album phytoconstituents can have a dual antihypertensive and nephroprotective action of regulating major renal targets.
Downloads
References
Chen R, Dharmarajan K, Kulkarni VT, Punnanithinont N, Gupta A, Bikdeli B, et al. The most important outcomes of research papers on hypertension. Circ Cardiovasc Qual Outcomes. 2013;6(4). doi:10.1161/CIRCOUTCOMES.113.000424.
Singh S, Shankar R, Singh GP. Prevalence and associated risk factors of hypertension: a cross-sectional study in urban Varanasi. Int J Hypertens. 2017;2017:1–10. doi:10.1155/2017/5491838.
World Health Organization. Hypertension. Geneva: WHO; 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/hypertension
Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16(4):223–237. doi:10.1038/s41581-019-0244-2.
Ku E, Lee BJ, Wei J, Weir MR. Hypertension in chronic kidney disease: core curriculum 2019. Am J Kidney Dis. 2019;74(1):120–131. doi:10.1053/j.ajkd.2018.12.044.
Kanugula AK, Kaur J, Batra J, Ankireddypalli AR, Velagapudi R. Renin–angiotensin system: updated understanding and role in physiological and pathophysiological states. Cureus. 2023;15:e40725. doi:10.7759/cureus.40725.
Ma J, Li Y, Yang X, Liu K, Zhang X, Zuo X, et al. Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 2023;8(1). doi:10.1038/s41392-023-01430-7.
Su C, Xue J, Ye C, Chen A. Role of the central renin–angiotensin system in hypertension. Int J Mol Med. 2021;47(6). doi:10.3892/ijmm.2021.4928.
Harrison DG, Coffman TM, Wilcox CS. Pathophysiology of hypertension. Circ Res. 2021;128(7):847–863. doi:10.1161/CIRCRESAHA.121.318082.
WebMD. Captopril: uses, side effects, interactions, pictures, warnings & dosing. Available from: https://www.webmd.com/drugs/2/drug-964/captopril-oral/details
Havelka J, Boerlin H, Studer A, Greminger P, Tenschert W, Luescher T, et al. Long-term experience with captopril in severe hypertension. Br J Clin Pharmacol. 1982;14(Suppl 2). doi:10.1111/j.1365-2125.1982.tb02060.x.
University of Illinois Chicago. Captopril oral tablet. Healthline; 2018. Available from: https://www.healthline.com/health/drugs/captopril-oral-tablet
WebMD. Losartan (Cozaar): uses, side effects, interactions, pictures, warnings & dosing. Available from: https://www.webmd.com/drugs/2/drug-6616/losartan-oral/details
University of Illinois Chicago. Losartan oral tablet. Medical News Today; 2022. Available from: https://www.medicalnewstoday.com/articles/losartan-oral-tablet
PharmD ARW. Losartan side effects: what you should know. Medical News Today; 2022. Available from: https://www.medicalnewstoday.com/articles/drugs-losartan-side-effects
WebMD. Propranolol (Inderal LA, Innopran XL): uses, side effects, interactions, pictures, warnings & dosing. Available from: https://www.webmd.com/drugs/2/drug-10404-9168/propranolol-oral/propranolol-oral/details
Johnson J. Everything you need to know about propranolol. Medical News Today; 2024. Available from: https://www.medicalnewstoday.com/articles/316061
Drugs.com. Propranolol: uses, dosage, side effects, warnings. Available from: https://www.drugs.com/propranolol.html
Bulsara KG, Patel P, Cassagnol M. Amlodipine. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025.
RxList. Amlodipine: side effects, uses, dosage, interactions, warnings. 2021. Available from: https://www.rxlist.com/amlodipine/generic-drug.htm
Drugs.com. Amlodipine: uses, side effects & dosage. Available from: https://www.drugs.com/amlodipine.html
Khare CP. Indian medicinal plants. Berlin: Springer; 2007. doi:10.1007/978-0-387-70638-2.
Kouranov A, Xie L, de la Cruz J, Chen L, Westbrook J, Bourne PE, Berman HM. The RCSB PDB information portal for structural genomics. Nucleic Acids Res. 2006;34:D302–D305. doi:10.1093/nar/gkj120.
Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7:42717. doi:10.1038/srep42717.
Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2018;46(W1):W257–W263. doi:10.1093/nar/gky318.
Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform. 2012;4:17.
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–1612. doi:10.1002/jcc.20084.
Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16(4):223–237. doi:10.1038/s41581-019-0244-2.
Suzuki A, Yamamoto N, Jokura H, Yamamoto M, Fujii A, Tokimitsu I, et al. Chlorogenic acid attenuates hypertension and improves endothelial function in spontaneously hypertensive rats. J Hypertens. 2006;24(6):1065–1073. doi:10.1097/01.hjh.0000226196.67052.c0.
Wang L, Pan X, Jiang L, Chu Y, Gao S, Jiang X, et al. Biological activity and mechanism of chlorogenic acid and its applications in the food industry. Front Nutr. 2022;9. doi:10.3389/fnut.2022.943911.
Zhang S, Liu Y, Wang X, Tian Z, Qi D, Li Y, et al. Antihypertensive activity of oleanolic acid is mediated via downregulation of secretory phospholipase A2 and fatty acid synthase in spontaneously hypertensive rats. Int J Mol Med. 2020;46(6):2019–2034. doi:10.3892/ijmm.2020.4744.
Yu M, Kim HJ, Heo H, Kim M, Jeon Y, Lee H, et al. Comparison of the antihypertensive activity of phenolic acids. Molecules. 2022;27(19):6185. doi:10.3390/molecules27196185.
Olas B. The cardioprotective potential of selected species of mistletoe. Front Pharmacol. 2024;15:1395658. doi:10.3389/fphar.2024.1395658.
Kleszken E, Purcarea C, Pallag A, Ranga F, Memete AR, Miere F, et al. Phytochemical profile and antioxidant capacity of Viscum album L. subsp. album and effects on its host trees. Plants (Basel). 2022;11(22):3021. doi:10.3390/plants11223021.
Harrison DG, Coffman TM, Wilcox CS. Pathophysiology of hypertension: the mosaic theory and beyond. Circ Res. 2021;128(7):847–863. doi:10.1161/CIRCRESAHA.121.318082.
Remuzzi G, Ruggenenti P, Benigni A. Understanding the nature of renal disease progression. Kidney Int. 1997;51(1):2–15. doi:10.1038/ki.1997.1.
ISSN 2307-1257
ISSN 2307-1265
