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Isolation, elucidation, and molecular docking studies of active compounds from Phyllanthus niruri with angiotensin-converting enzyme inhibition
Islamudin Ahmad1, Abdul Mun'im2, Sri Luliana3, Berna Elya2, Azminah Azminah4, Arry Yanuar2, Yudithya Artha2, Osamu Negishi5
1 Department of Pharmaceutical Sciences, Faculty of Pharmacy, Mulawarman University, Kampus UNMUL Samarinda 75119, East Kalimantan; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok 16424, West Java, Indonesia
2 Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok 16424, West Java, Indonesia
3 Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok 16424, West Java; Department of Pharmacy, Faculty of Medicine, Universitas Tanjungpura, Kampus UNTAN Pontianak 78115, West Kalimantan, Indonesia
4 Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok 16424, West Java; Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Surabaya, Surabaya, East Java, Indonesia
5 Department of Applied Biohemistry, Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan
Correspondence Address:
Abdul Mun'im
Building A, 3rd Floor, Rumpun Ilmu Kesehatan, Kampus UI Depok, West Java
Indonesia
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/pm.pm_151_18
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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-glucopyranosyl-(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.
Abbreviations Used: P. niruri: Phyllanthus niruri; ACE: Angiotensin-converting enzyme; HHL: Hippuryl-L-histidyl-L-leucine; HA: Hippuric acid; PDB: Protein database; IC50: 50% inhibition concentration; FH: N-hexane fraction; FE: Ethyl acetate fraction; TLC: Thin layer chromatography; UV-VIS: Ultraviolet-visible; NMR: nuclear magnetic resonance; FTIR: Fourier–Transform infrared; MS: Mass spectrometry; HMQC: Heteronuclear Multiple-Quantum Correlation; HMBC: Heteronuclear multiple bond correlation; TADOK: Tugas Akhir Mahasiswa Doktor.
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