HMG-CoA Reductase Inhibitory Activity of Gnetum gnemon Seed Extract and Identification of Potential Inhibitors for Lowering Cholesterol Level

    Published on:October 2017
    Journal of Young Pharmacists, 2017; 9(4):559-565
    Original Article | doi:10.5530/jyp.2017.9.107

    Kholid Abdul Hafidz1, Nuraini Puspitasari1, Azminah2, Arry Yanuar2, Yuditya Artha2, Abdul Mun’im*1

    1Department of Pharmacognosy-Phytochemistry, Faculty of Pharmacy, Universitas Indonesia, Depok, 16424 West Java, INDONESIA.

    2Department of Biomedical Computation, Faculty of Pharmacy, Universitas Indonesia, Depok – 16424 West Java, INDONESIA.


    Objectives: Melinjo (Gnetum gnemon) seeds have been known to have some biological properties. One of them is ant hypercholesterolemia. The present study investigated in vitro and in silico methods to predict potential antihypercholesterolemic of the Melinjo seed extracts of through HMG-CoA reductase inhibitory activity. Methods: Melinjo seed powders were successively extracted by reflux method using five solvents with gradient polarity including: n-hexane, dichloromethane, ethyl acetate and methanol. All extracts were evaluated in vitro using HMG-CoA Reductase assay kit, to analyze the inhibitory activity. Molecular docking of the phytochemical content of the seeds were carried out using Auto Dock Vina, and also Ligand Scout to analyses interaction between ligand and receptor. Results: Dichloromethane extract demonstrated the highest inhibitory activity against HMG-CoA reductase with IC50 value is 0.40 μg/mL, followed by that of ethyl acetate extract. UPLC-MS analyses showed that dichloromethane extract contained trans-resveratrol, piceid, gnetin C, gnetol, isorhapontigenin, ɛ-viniferin, gnemonol L, and gnemonol M. Molecular docking studies demonstrated that dimer of resveratrol such as gnemonol L, gnemosida, and ɛ-viniferin have better free binding energy than that of monomer. piceid, gnetin C, gnemonol L, and gnemonol M could be considered as HMG-CoA reductase inhibitor. Conclusion: Gnetum gnemon seed extract showed strong HMG-CoA reductase activity. Resveratrol dimer promises as a potential lead compound to design/synthesize anti-cholesterol.

    Key words: Gnetum gnemon, Melinjo, HMG-CoA Reductase, Resveratrol, Stilbene, Molecular Docking.

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