title: Molecular rationale delineating the role of lycopene as a potent HMG-CoA reductase inhibitor: in vitro and in silico study.
abstract: This study initially aimed to depict the molecular rationale evolving the role of lycopene in inhibiting the enzymatic activity of β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) reductase via in vitro and in silico analysis. Our results illustrated that lycopene exhibited strong HMG-CoA reductase inhibitory activity (IC50 value of 36 ng/ml) quite better than pravastatin (IC50 = 42 ng/ml) and strong DPPH free radical scavenging activity (IC50 value = 4.57 ± 0.23 μg/ml) as compared to ascorbic acid (IC50 value = 9.82 ± 0.42 μg/ml). Moreover, the Ki value of lycopene (36 ng/ml) depicted via Dixon plot was well concurred with an IC50 value of 36 ± 1.8 ng/ml. Moreover, molecular informatics study showed that lycopene exhibited binding energy of -5.62 kcal/mol indicating high affinity for HMG-CoA reductase than HMG-CoA (ΔG: -5.34 kcal/mol). Thus, in silico data clearly demonstrate and support the in vitro results that lycopene competitively inhibit HMG-CoA reductase activity by binding at the hydrophobic portion of HMG-CoA reductase.
authors.affiliation: a Clinical Biochemistry & Natural Product Research Laboratory, Department of Biosciences , Integral University , Lucknow , India.
authors.forename: Sahir Sultan
authors.initials: SS
authors.lastname: Alvi
authors.affiliation: a Clinical Biochemistry & Natural Product Research Laboratory, Department of Biosciences , Integral University , Lucknow , India.
authors.forename: Danish
authors.initials: D
authors.lastname: Iqbal
authors.affiliation: a Clinical Biochemistry & Natural Product Research Laboratory, Department of Biosciences , Integral University , Lucknow , India.
authors.forename: Saheem
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: a Clinical Biochemistry & Natural Product Research Laboratory, Department of Biosciences , Integral University , Lucknow , India.
authors.forename: M Salman
authors.initials: MS
authors.lastname: Khan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000737:chemistry; D002338:Carotenoids / Q000494:pharmacology*; D003198:Computer Simulation; D016166:Free Radical Scavengers / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D048088:Informatics; D000077276:Lycopene; D010851:Picrates / Q000737:chemistry; D017035:Pravastatin / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D010851:Picrates; D002338:Carotenoids; C004931:1,1-diphenyl-2-picrylhydrazyl; D017035:Pravastatin; D001205:Ascorbic Acid; D000077276:Lycopene
keywords: HMG-CoA reductase; Lycopene; antioxidant; hyperlipidemia