Angiotensin converting enzyme inhibitory activity of melinjo (Gnetum gnemon L.) seed extracts and molecular docking of its stilbene constituents

Objectives: To evaluate the angiotensin converting enzyme (ACE) inhibitory activity of melinjo (Gnetum gnemon) seed extract and to study molecular docking of stilbene contained in melinjo seeds. Methods: Melinjo seed powders were extracted with n-hexane, dichloromethane, ethyl acetate, methanol, and water successively. The extracts were evaluated ACE inhibitory activities using ACE kit-Wist and the phenolic content using Folin–Ciocalteu method. The extract demonstrated the highest ACE inhibitory activity was subjected to liquid chromatography-mass spectrometry (LC-MS) to know its stilbene constituent. The stilbene constituents in melinjo seed were performed molecular docking using AutoDock Vina, and ligand-receptor Interactions were processed using Ligand Scout. Results: The ethyl acetate extract demonstrated the highest ACE inhibition activity with inhibitory concentration 50% value of 9.77 × 10⁻⁸ μg/mL and the highest total phenolic content (575.9 mg gallic acid equivalent/g). Ultra-performance LC-MS analysis of ethyl acetate extract has detected the existency of resveratrol, gnetin C, ε-viniferin, and gnemonoside A/B. These compounds displayed similar physiochemical properties to lisinopril (ACE inhibitor), as in silico molecular docking studies demonstrated that they fit into the lisinopril receptors. Conclusion: In vitro analysis ethyl acetate extract from melinjo seeds demonstrated the highest ACE inhibitory activity. Molecular docking analysis indicated that resveratrol dimers, gnetin C and gnemonoside A can be considered ACE inhibitor.