Anti-obesity, Antioxidant and In Silico Evaluation of Justicia carnea Bioactive Compounds as Potential Inhibitors of an Enzyme Linked with Obesity: Insights from Kinetics, Semi-empirical Quantum Mechanics and Molecular Docking Analysis
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Date
2021
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ELSEVIER Biophysical Chemistry
Abstract
Obesity is a global health problem characterized by excessive fat deposition in adipose tissues
and can be managed by targeting pancreatic lipase (PL) activity. In the present study, we investigated
the in vitro antioxidant and anti-obesity potentials of methanolic leaf extract of Justicia carnea(MEJC)
using lipase inhibition kinetics model. In silico evaluations of MEJC bioactive compounds as potential
drug-like agents and inhibitors of PL were also investigated using SwissADME prediction tool, semi empirical quantum mechanics(SQM), molecular electrostatic potential(MEP) and molecular docking
analysis. Gas chromatography-mass spectrometry (GC–MS) revealed presence of campesterol,
stigmasterol, beta-amyrin etc. MEJC scavenged reactive species and inhibited PL activity via a mixed
inhibition pattern (Ki = 107.69 μg/mL; Kii = 398.00 μg/mL) with IC50 > orlistat’s IC50. Molecular docking
of GC–MS identified compounds with porcine PL showed compounds 8,10,12 and 14 having high PL binding affinity and similar binding pose with orlistat. Hydrophobic interactions and van der Waals
forces were predominantly involved in the ligands’ interactions with some key catalytic site amino acid
residues (Ser-153,His-264). Compounds 10,12,13 and 14 indicated high drug-likeness, bioavailability,
electronegativity, ELUMO-EHOMO energy gaps and MEP. Our findings show that MEJC is a rich natural
source of antioxidant and anti-obesity agents which could be optimized for development of new anti obesity drugs.
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Keywords
Justicia carnea, Antioxidant activity, Lipase inhibitor, Obesity therapy, Semi-empirical calculations, Molecular docking