Protective Effects of Capsaicinoid Glucoside from Fresh Hot Peppers Against Hydrogen peroxide-induced Oxidative Stress in HepG2 Cells Through-dependent Signaling Pathway

This study aimed to investigate the protective effect of a novel capsaicinoid glucoside (CG) against H₂O₂-induced oxidative stress in HepG2 cells and elucidate its underlying molecular mechanism. CG treatment significantly reduced H₂O₂-induced cell mortality and attenuated the production of lactate dehydrogenase and malondialdehyde in a dose-dependent manner. Moreover, CG drastically reduced the ROS levels 18.7, 37.4, and 43.8% at concentrations of 25, 50, and 100 µg/mL, respectively. while increased glutathione content and catalase activity. Most importantly, in silico analysis revealed that CG effectively interacted with each of TRPV1 and Nrf2 by H-bonds, π–π interactions, and hydrophobic forces without simulation fluctuations over 50 ns. TRP, LYS, THR, LEU, GLN, VAL, ILE, and TYR residues of the tested proteins were all involved in the interaction with CG. These findings suggested that CG could reduce H₂O₂-induced oxidative stress in HepG2 cells via TRPV1/Nrf2 pathway which could be validated in functional foods/supplements formulations.