Inhibitory kinetics and mechanism of pentacyclic triterpenoid from endophytic Colletotrichum gigasporum against pancreatic lipase

The burden of obesity is increasing all over the world. Except for Orlistat, no effective anti-obesity drug is currently available. Therefore, a search for the new anti-obesity compound is need of time. This study demonstrates macromolecular interaction and inhibitory effect of pentacyclic triterpenoids (PIT) on pancreatic lipase (PL). In the present study PiTs from endophytic Colletotrichum gigasporum were found to show significant inhibitory activity against PL with IC50 of 16.62 +/- 1.43 mu g/mL. The PTT isolated through bioassay-guided isolation showed a dose-dependent (R-2 = 0.915) inhibition against porcine PL and the results were comparable with the standard (Orlistat). Based on inhibition kinetic data, the gradual increase in K-m (app) with increasing FIT concentration indicated that the mode of interaction of FIT with PL was a competitive type, and it directly competed with the substrate (pNPB) for the active site of PL In vivo studies in Wistar rats at the oral dose (100 mg/kg body weight) of PTT significantly decreased (p < 0.05) incremental plasma triglyceride levels as compared to group B and TG absorption was down-regulated up to 49.18% visa vis group D animals. The isolated PTT was identified as lupeol based on chromatographic and spectral data. The endophytic isolate was identified as Colletotrichum gigasporum based on morphology and ITS gene sequencing. The present study indicated that PTT had the potential to be used as a natural PL inhibitor in the treatment of obesity and the isolated endophyte can be a valuable bioresource for it. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The study demonstrates the inhibitory effect of pentacyclic triterpenoids (PIT) on pancreatic lipase (PL), indicating their potential as a natural PL inhibitor in the treatment of obesity. The isolated PTT was identified as lupeol, and the endophytic isolate was identified as Colletotrichum gigasporum, showing promise as a valuable bioresource for obesity treatment.