Evaluating the Antiobesity Potential of Hesperidin and Resveratrol: Analysis of Pancreatic Lipase Inhibition, Molecular Docking Insights, and Pharmacokinetic Profiles

Abstract

Obesity is a global health crisis associated with metabolic disorders, and while current anti-obesity drugs target pancreatic lipase, their adverse side effects have driven interest in safer, plant-based alternatives. This study evaluates the anti-obesity potential of hesperidin and resveratrol via pancreatic lipase inhibition, molecular docking, and pharmacokinetic analysis. In vitro assays using p-nitrophenyl palmitate showed both compounds reduce lipase activity, with IC50 values of 425.24 μM (hesperidin) and 800.75 μM (resveratrol) versus 31.91 μM for orlistat. Kinetics confirmed reversible competitive inhibition. Docking indicated strong binding affinities (-9.6 kJ/mol for hesperidin, -8.7 kJ/mol for resveratrol) exceeding orlistat (-7.0 kJ/mol), though experimental efficacy was lower, likely due to orlistat's irreversibility. Pharmacokinetics revealed good bioavailability and safety, with resveratrol exhibiting better absorption and blood-brain barrier (BBB) permeability. Optimizing these compounds and investigating their synergistic potential with each other or with standard drugs like orlistat could lead to novel, safer, and more effective weight-management therapies.