Metabolomics and Molecular Docking of Murraya paniculata Leaf Extract: A Mechanistic Study Toward Lipid Lowering Activity

Abstract The adverse side effects of synthetic triglyceride-lowering medications, such as muscle pain and liver damage, highlight the need for safer alternatives from natural sources. This study investigates the potential of bioactive compounds in Murraya paniculata leaf extract (MPE) to inhibit pancreatic lipase, a critical enzyme in fat metabolism. Dried M. paniculata leaves were macerated in 70% ethanol, and their phytochemical composition was analyzed using LC-HRMS. Pancreatic lipase inhibition was assessed via enzymatic assays, and the mode of inhibition was evaluated using Michaelis-Menten kinetics. Molecular docking studies identified compounds with strong binding affinities to lipase. The phytochemical profile, determined by metabolomic profiling, was diverse and predominantly composed (53%) of methoxylated flavonoids, including nobiletin and tangeretin. In enzymatic assays, the extract exhibited a non-competitive inhibition mechanism against lipase. This was evidenced by a significant decrease in Vmax (2.84 μM/min vs. 3.83 μM/min for the solvent control) and no significant change in Km (0.860 mM vs. 0.809 mM). Molecular docking identified compounds such as nobiletin, tangeretin, schaftoside, orientin, and quercetin derivatives with binding affinities surpassing orlistat, a clinical lipase inhibitor. The extract of M. paniculata exhibits significant lipase inhibitory activity, primarily attributed to methoxylated flavonoids and other bioactive compounds. These findings underscore the therapeutic potential of MPE in managing metabolic disorders, suggesting further exploration into its application for hypertriglyceridemia and cardiovascular health.