Isolation, Elucidation, and Molecular Docking Studies of Active Compounds from Phyllanthus niruri with Angiotensin‑Converting Enzyme Inhibition

Background: Phyllanthus niruri, in Indonesia, is known as “Meniran” has a long history of use in ethnic or traditional medicine worldwide, mainly as an antihypertensive agent. Objective: The present study was designed to isolate and identify active compounds with angiotensin‑converting enzyme (ACE) inhibition activity from P. niruri herb and confirm the mechanism of action, affinity, and domain specificity interactions of the isolated compounds. Materials and Methods: Some fractions of P. niruri methanolic extract were subjected to column chromatography and preparative thin‑layer chromatography to get active compounds. Structural elucidation was determined via spectroscopic methods. ACE inhibition activity was measured using hippuryl‑L‑histidyl‑L‑leucine as a substrate in vitro assay. Furthermore, confirmation of the mechanism of action, affinity, and domain specificity interaction of the isolated compounds on ACE complex macromolecule (protein database id: 1O86) was performed by in silico molecular docking studies. Results: In this work, four active compounds were isolated from aerial part of P. niruri, including hypophyllantin (50% inhibition concentration [IC50] = 0.180 µg/mL), phyllantin (IC50 = 0.140 µg/mL), methyl gallate (IC50 = 0.015 µg/mL), and quercetin 3‑O‑β‑D‑glucopyranos yl‑(1’’’‑6’’)‑α‑rhamnoside (IC50 = 0.086 µg/mL). In silico molecular docking method emphasizes ligand‑residue interactions, thereby predicting the inhibitory activity of these compounds. After docking to an ACE complex macromolecule, quercetin 3‑O‑β‑D‑glucopyranosyl‑(1’’’‑6’’)‑ α‑rhamnoside obtained more interactions than lisinopril. Conclusion: The results were obtained from in silico and in vitro experiments and confirm the potential active compound is an ACE inhibitor and a new antihypertensive agent.