Characterization, Anti-glycation, Anti-inflammation, and Lipase Inhibitory Properties of Rauvolfia vomitoria Leaf Extract: In Vitro and In Silico Evaluations for Obesity Treatment.

Pancreatic lipase (PLP) is an enzyme responsible for the catalytic hydrolysis of fats and its inhibition is relevant for obesity management. Side effects linked with orthodox inhibitors have, however, paved the way for an increased search for safe natural sources. The present study investigated the anti-glycation, anti-inflammatory, and anti-lipase properties of Rauvolfia vomitoria aqueous (ARV), ethanolic (ERV), and methanolic (MRV) leaf extracts coupled with the molecular interactions of selected bioactive compounds with PLP using in vitro and in silico techniques. Phytochemical constituents were characterized using spectroscopic techniques. Drug-likeness and chemical reactivity profile of selected bioactive compounds were analyzed using SwissADME and quantum chemical calculations. FT-IR and GC-MS affirmed the presence of phenolic compounds including 3-phenyl-2-ethoxypropylphthalimide and 5-methyl-2-phenyl-1H-indole. All extracts showed moderate anti-glycation, anti-inflammatory, and lipase inhibitory capacities relative to standard controls. However, MRV exhibited the highest lipase inhibition (IC50, 0.17 ± 0.01 mg/mL), using a mixed-inhibition pattern. MRV interaction with PLP resulted in decreased secondary structure components of PLP (α-sheet, ß-turn). MRV compounds (MCP20, MCP28, etc.) exhibited low chemical hardness, EHOMO-ELUMO energy gap, and high chemical reactivity. Foremost MRV compounds obeyed Lipinski's rule of five for drug-likeness and interacted with PHE-78 amongst others at PLP catalytic domain with high binding affinity (≥ - 9.3 kcal/mol). Pi-alkyl hydrophobic interaction and hydrogen bonding were predominantly involved. Our findings provide scientific insights into the ethnotherapeutic uses of R. vomitoria extracts for the management of obesity and related complications, plus useful information for optimizable drug-like candidates against obesity.

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.

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.