EVALUATION OF ETHANOLIC EXTRACT OF TILIACORA ACUMINATA LEAVES FOR PANCREATIC LIPASE INHIBITION AND LIPID MODULATION: IN SILICO AND IN VITRO STUDIES

Objectives: Hypercholesterolemia is a significant risk factor for cardiovascular disease and dyslipidemia. In 33–58% of individuals, current medications targeting 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) and low-density lipoprotein (LDL) receptor do not intend to reduce LDL cholesterol. Pancreatic lipase, responsible for cholesterol absorption, can be a potential target in hypercholesterolemia. The current study aims to conduct virtual screening and molecular dynamics of compounds derived from ethanolic extract of Tiliacora acuminata leaves (TAL-EE) with pancreatic lipase, evaluate cell viability with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay, assess lipase inhibition, perform lipid accumulation assessment (Oil Red O staining) and measure cholesterol and triglycerides (TG) in HepG2 cells. Methods: Docking was carried out using AutoDock tools, and interaction analysis was performed with PyMOL 2.0. Para-nitrophenyl butyrate and porcine pancreatic lipase were used to test TAL-EE for lipase inhibition. Viability analysis (MTT test, IC50), Oil Red O staining, and measurements of total cholesterol (TC) and triglyceride (TG) levels were conducted using HepG2 cells treated with TAL-EE. Results: 5α-Androstan-16-one and cyclic ethylene mercaptole were identified through virtual screening to have the highest docking score (−9.4 kcaL/moL) for pancreatic lipase, exhibiting stability in dynamic studies. The IC50 for the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay reported 20 μg/mL. After 48 h at lower doses, TAL-EE exhibited a 67% reduction of lipase activity and increased TG and TC levels in the medium of HepG2 cells, indicating reduced intracellular cholesterol levels. Conclusion: TAL-EE showed significant pancreatic lipase inhibition and lipid modulation, suggesting potential as an antihypercholesterolemic agent.