title: An in vitro and molecular informatics study to evaluate the antioxidative and β-hydroxy-β-methylglutaryl-CoA reductase inhibitory property of Ficus virens Ait.
abstract: The present study is initially intended to evaluate antioxidant and β-hydroxy-β-methylglutaryl-CoA reductase (HMGR) inhibitory property of Ficus virens Ait., first by in vitro analyses followed by a corroboratory molecular informatics study. Our results show that of all the sequentially extracted fraction of F. virens bark and leaves extract, F. virens bark methanol extract exhibits strong radical scavenging, antioxidant and oxidative DNA damage protective activity, which is well correlated with its total phenolic content. In addition, F. virens bark methanol extract, which is non-cytotoxic, significantly and non-covalently inhibit the HMGR activity (IC50  = 3.45 ± 0.45 µg/ml) in comparison with other extracts. The mechanistic aspect of this inhibition activity is authenticated by molecular docking study of bioactive compounds as revealed from gas chromatography-mass spectrometry data, with HMGR. The analysis for the first time indicates that quinic acid (ΔG: -8.11 kcal/mol) and paravastatin (ΔG: -8.22 kcal/mol) exhibit almost same binding energy, while other compounds also showed good binding energy, suggesting that quinic acid alone or in combination with other major bioactive compound is probably responsible for HMGR inhibitory property of the extract and plausibly can be used in in vivo system for the management, prevention, and alleviation of hypercholesterolemia as well as hypercholesterolemia-induced oxidative stress.
authors.affiliation: Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, 226026, India.
authors.forename: Danish
authors.initials: D
authors.lastname: Iqbal
authors.forename: M Salman
authors.initials: MS
authors.lastname: Khan
authors.forename: Mohd S
authors.initials: MS
authors.lastname: Khan
authors.forename: Saheem
authors.initials: S
authors.lastname: Ahmad
authors.forename: Ashwini K
authors.initials: AK
authors.lastname: Srivastava
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D030681:Ficus / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia; D051379:Mice; D062105:Molecular Docking Simulation; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011801:Quinic Acid / Q000737:chemistry
chemical_list: D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010936:Plant Extracts; D011801:Quinic Acid; D010088:Oxidoreductases
keywords: F. virens; HMG-CoA reductase; antioxidant; molecular docking