Potential lipase inhibitor from underutilized part of Andrographis paniculata: Targeted isolation and mechanism of inhibition

Abstract

Pancreatic lipase (PL) plays a vital role in lipid metabolism-associated disorders, especially obesity. The present study demonstrates the targeted isolation of biologically active compounds from Andrographis paniculata root with dietary fat absorption capacity for obesity management. The HPLC-based micro-fractionation and off-line in-vitro pancreatic lipase inhibition assay have resulted in potential phytochemicals with IC50 value 4.46–21.76 µg/mL. 7-O-methyl-dihydro wogonin (MDHW) was the most potent with IC50 = 14.86 ± 0.19 μM than reported flavanones. The MDHW has also exhibited a synergistic effect with orlistat at a concentration lower than 14.86 μM. MDHW acts as a competitive inhibitor via energy transfer from PL. The binding interaction of MDHW with PL was hydrophobic (Ka=1.40 ×103 L/mol). FT-IR studies showed the stable and compact MDHW-PL complex as the percentage of β -turn, β-antiparallel and random coil increased, while the portion of the α-helix, β-sheet decreased. Additionally, in-silico studies have also confirmed the non-polar interaction of MDHW with the protein's active site (PBD:1ETH) by spontaneous H-bonds. Results suggested that MDHW isolated from A. paniculata root showed high PL inhibitory activity and binding affinity (Ki =7.4 µM), promising a potential anti-obesity agent for pharmaceutical and food industry applications.