Evaluation of Anti‐Hyperlipidemic Activity of the Seeds Extracts of Ficus carica: In Vitro and In Silico Approaches.

Obesity and hyperlipidemia have become major disorders predominantly causing prevailing cardiovascular diseases and ultimately death. The prolonged use of anti‐obesity drugs and statins for reducing obesity and blood lipid levels is leading toward adverse effects of kidneys and muscles, specifically rhabdomyolysis. The objective of this study is to evaluate potential of seeds of Ficus carica against hyperlipidemia. Various extracts and isolated compounds from fig seeds were analyzed and evaluated for their anti‐hyperlipidemic potential. Methanol extract and its ethyl acetate fraction showed maximum pancreatic lipase inhibition of 61.93% and 86.45% in comparison to reference drug Orlistat. Four compounds isolated by HPLC‐PDA technique were determined as Gallic acid, Catechin, Epicatechin, and Quercetin also showed strong potential to inhibit enzyme pancreatic lipase comparable to Orlistat. These isolated compounds were further analyzed for molecular docking and MM‐GBSA studies. Three ligands, namely Quercetin, Epicatechin, and Catechin were found more effective against pancreatic lipase as these possessed docking scores (−9.881, −9.741, −9.410) higher to that of the reference ligand Orlistat (−5.273). The binding free energies of these compounds were −55.03, −56.54, and 60.35 kcal/mol, respectively. The results have shown that Quercetin has the highest binding affinity correlating with the highest inhibition of pancreatic lipase enzyme 1LPB. Hence, it is suggested that seeds of F. carica have promising anti‐hyperlipidemic potential and foremost in reducing obesity. Summary: Various extracts, fractions of methanol extract, and isolated compounds of seeds of Ficus carica, in combating hyperlipidemia, were evaluated utilizing in vitro anti‐lipase activity and computational analysis.All extracts, methanol fractions and compounds isolated through high‐performance liquid chromatographic technique (HPLC) exhibited anti‐hyperlipidemic potential comparable to reference Orlistat.Molecular docking and MM‐GBSA studies illustrated that isolated ligand Quercetin along with Epicatechin and Catechin strongly inhibit enzyme pancreatic lipase (1LPB) and displayed a high docking score in comparison to reference ligand.Quercetin amongst four isolated compounds could be more effective in treating hyperlipidemia and obesity as compared to reference Orlistat. Significance Statement: Ficus carica possess potential constituents with profound therapeutic and traditional uses due to which the whole plant is considered medicinally important. This study focuses on the anti‐hyperlipidemic potential of seeds of F. carica against pancreatic lipase by using computational and in vitro studies. The results of this study provides the evidence that Quercetin exhibits a potent anti‐hyperlipidemic effect by inhibiting pancreatic lipase and also possess a greater binding affinity for pancreatic protein 1LPB as compared to reference Orlistat. [ABSTRACT FROM AUTHOR]