IN SILICO IDENTIFICATION TESTING OF TRITERPENE SAPONINES ON CENTELLA ASIATICA ON INHIBITOR RENIN ACTIVITY ANTIHYPERTENSIVE
Keywords:Antihypertensive, Centtella asiatica, Triterpene saponines, Renin inhibitors, Aliskiren
The renin-angiotensin-aldosterone system (RAAS) has an essential role in the occurrence of hypertension. Two drugs that act on SRAA are ACE Inhibitor and ARB. ACE inhibitor and ARB are two antihypertensive drugs that act on RAAS. However, both drugs are not fully effective because they produce incomplete suppression of RAAS. The therapeutic potential of the two drugs is limited, so it is necessary to find out other drugs that are more effective in inhibiting the RAAS system. Renin-inhibitors are evolving as options that can inhibit at the highest levels in RAAS. Discontinuation of renin inhibitor therapy does not cause rebound hypertension as in ACEIs and ARBs. The search for natural renin inhibitors began to be carried out as an alternative to aliskiren. Renin-inhibitors derived from natural ingredients generally come from the class of saponin compounds or polyphenol compounds. One of Indonesia's native plants that contain saponins and polyphenols is Centella asiatica. Thus, research on the antihypertensive potential of these plants was carried out. It is expected that the Centella asiatica plant has a renin inhibitor effect as a blood pressure-lowering drug derived from herbs but has the same effect as aliskiren. The research method was carried out in silico to test the activity of compounds that have potential as antihypertensives in the Centella asiatica plant. The method used is molecular docking, with the docking software used being Molegro Virtual Docker (MVD) 6.0. The results showed that madecasoside and asiaticoside from the Centella asiatica plant have intense renin inhibitor activity, with a mean re-rank score of-105.27 and-93.67, respectively. The conclusion is that madecasoside has similarities with aliskiren with a re-rank value of-105.27. The smallest re-rank value indicates the similarity and strong protein binding between the tested ligand compound and the comparison protein.
Health Research, Development Agency of the Ministry of Health. Basic health research RISKESDAS; 2018.
Ahmad S, Simmons T, Varagic J, Moniwa N, Chappell MC, Ferrario CM. Chymase-dependent generation of angiotensin II from angiotensin-(1-12) in human atrial tissue. PLOS ONE. 2011:e28501(12):e28501. doi: 10.1371/journal.pone.0028501, PMID 22180785.
Bown D. New encyclopedia of herbs and their uses. New York: Dorling Kindersley; 2001.
Besung I, Kerta Nengah. Pegagan (Centella asiatica) as an alternative for the prevention of infectious diseases in livestock, Pegagan. Vol. 2(1); 2009.
Grimaldi R, De Ponti F, D’Angelo L, Caravaggi M, Guidi G, Lecchini S, Frigo GM, Crema A. J Ethnopharmacol Asian Acid. 1990 Feb;28(2):235-41. doi: 10.1016/0378-8741(90)90033-p, PMID 2329813.
Hevener KE, Zhao W, Ball DM, Babaoglu K, Qi J, White SW, Lee RE. Validation of molecular docking programs for virtual screening against dihydropteroate synthase. J Chem Inf Model. 2009;49(2):444-60. doi: 10.1021/ci800293n, PMID 19434845.
Muhadi JNC. Evidence-based guideline for the management of adult hypertensive patients; 2016.
Ciocoiu M, Badescu M, Badulescu O, Tutunaru D, Badescu L. Polyphenolic extract association with renin inhibitors in experimental arterial hypertension. JBiSE. 2013;6(4):493-7. doi: 10.4236/jbise.2013.64062.
Hypertension guideline programming. American Hearts Associations annual scientific section. Aneheim Calif. 17 Nov 2017.
Takahashi S, Hori K, Hokari M, Gotoh T, Sugiyama T. Inhibition of human renin activity by saponins. Biomed Res. 2010;31(2):155-9. doi: 10.2220/biomedres.31.155, PMID 20460744.
Troutman GW. Drug induced diseases. In: Philip OA, James EK, William GT, editors Handbook of clinical drug data. New York: McGraw-Hill Companies; 2002.
Williams SK, Ogedegbe G. Unraveling the mechanism of renin-angiotensin- aldosterone system activation and target organ damage in hypertensive blacks. Hypertension. 2012;59(1):10-1. doi: 10.1161/hypertensionaha.111.182790, PMID 22146513.
Maquart FX, Bellon G, Gillery P, Wegrowski Y, Borel JP. Stimulation of collagen synthesis in fibroblast culture by triterpenes extracted from pegagan. Connect Res Network. 1990;24(2):107-20.
Pramono S. Chromatogram profile of pegagan herb extract with antihypertensive effect. Warta TOI. 1992;1(2):37-8.
Lee YS, Jin DQ, Kwon EJ, Park SH, Lee ES, Jeong TC, Nam DH, Huh K, Kim JA. Asiatic acid, a triterpene, induces apoptosis through intracellular Ca2+ release and p53 expression on enhanced Hep G2 human hepatoma cells. Letter Cancer. 2002 Dec;186(1):83-91.
Pascual Teresa S, Sanchez Ballesta MT. Anthocyanins: from plant to health. phytochemistry reviews. Proc Phytochem Soc Eur. 2008;7:281-99.
WHO. WHO monographs on selected medicinal plants. Vol. 1. Geneva: World Health Organization; 1999. p. 77-84.
Racmawaty RY. Effect of shade and types of pegagan (Centella asiatica (L.) Urban.) on production growth and its triterpenoid content as medicines [thesis of the Department of Agricultural Cultivation. IPB; 2005. p. 58.
Chen R, Dharmarajan K, Kulkarni VT, Punnanithinont N, Gupta A, Bikdeli B, Mody PS, Ranasinghe I. Most important outcomes research papers on hypertension. Circ Cardiovasc Qual Outcomes. 2013;6(4):e26-35. doi: 10.1161/circoutcomes. 113.000424, PMID 23838106.
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