Study of Triterpene Saponin Compounds from Centella asitica as Renin Inhibitor with Pharmacophore Modeling, Molecular Docking and In-vitro Evaluation

Abstract

Hypertension is a silent killer that causes kidney, heart, and stroke damage if not handled properly. In Indonesia, the prevalence of the population with high blood pressure is 34.11% with women 36.85% higher than men 31.34%, this shows a fairly high value so that special attention is needed on hypertension therapy. It is known that currently there are 6 types of pharmacological therapy for hypertension and one of the newest is the renin inhibitor class (Aliskiren). Indonesia has diverse natural wealth in the form of flora and fauna, with a wealth of more than 30,000 types of medicinal plants with 9500 potential herbal medicines that have not been utilized optimally, with the largest exporter of herbal medicines in the world. Centella asiatica plants containing triterpenoid saponins have high renin inhibitor activity, namely the content of Asiaticoside and Madecasoside. The research method was carried out in silico using molecular simulation and in vitro with fluorometry (328/552 nm) to test the activity of asiaticoside and madecasoside compounds as well as a mixture of asiaticoside and madecasoside in Centella asiatica plants. This is supported by the docking outcome. The docking results show that madecososide compounds have a gibbs energy close to the positive control aleskiren (-8.356 kcal/mol) and aleskiren (-9.44 kcal/mol). The experiment results showed that the triterpenoid saponin compound (madecassoside) contained an IC value of 0.71, at a concentration of 5 μg/μl, and absorbance of 1.35 A in the first minute. The strongest renin inhibition was Madecasoside compound with a concentration of 5 μg/μl with an average value of fluorescent adsorption and an average percent inhibition of 135% with the best renin inhibition at Madecasoside 5 ug/ul the first minute with absorbance values 1.19 A. Finally, the in silico result corresponded to the in vitro experiment. Centella asiatica plants have renin inhibitor activity as antihypertensive, especially in secondary metabolites of triterpene saponins with pure madecasoside compounds compared with aliskiren as a renin inhibitor. So that the compound madecasoside has renin inhibitor activity as an antihypertensive.