Dillenia indica L. Fruits as Pancreatic Lipase Inhibitors: Kinetics Study, Fluorescent Spectroscopy and Molecular Docking

The current investigation explored the phytochemical analysis and pancreatic lipase (PL) inhibition activity of Dillenia indica (D. indica) L. fruit extracts. Out of four extracts, only the hydro-ethanol extract of D. indica fruits (HEEFDI) showed the potent antioxidant activity (IC50, 82.71 +/- 1.25 mu g/mL) as compared to ascorbic acid (IC50, 49.19 +/- 0.58 mu g/mL). The PL inhibition of HEEFDI extract (IC50, 32.35 +/- 0.67 mu g/mL) displayed a better result as compared to the standard drug orlistat (IC50, 36.08 +/- 0.24 mu g/mL). An exploration of the chemical composition of the HEEFDI extract was conducted using LC-QTOF-MS, which led to the identification of approximately eighteen bioactive markers. Only the six major active biomarkers were subjected to docking studies against the PL enzyme (PDB ID: 1LPB). Interestingly, two known markers kaempferol (KF) and quercetin (QN) exhibited strong binding to the targeted protein, as evidenced by their respective docking scores as - 9.9 kcal/mol and - 9.8 kcal/mol, with minimal conformational energy. The molecular simulation analysis of the ligand demonstrates strong binding potential and a high affinity for the respective protein. The enzyme kinetics analysis confirmed the inhibitory mechanism of HEEFDI extract, and it was found to be a mixed manner type. After the interaction of the HEEFDI extract with PL, secondary and tertiary conformational changes were observed, as evidenced by fluorescence studies. This study revealed the ability of the HEEFDI extract to effectively inhibit PL enzyme activity, indicating its potential benefits in reducing fat accumulation.