Four active monomers from Moutan Cortex exert inhibitoryeffects against oxidative stress by activating Nrf2/Keap1signaling pathway

ABSTRACT

Paeonol, quercetin, -sitosterol, and gallic acid extracted from MoutanCortex had been reported to possess anti-oxidative, anti-inflammatory, and antitumoractivities. This work aimed to illustrate the potential anti-oxidative mechanismof monomers in human liver hepatocellular carcinoma (HepG2) cells-induced byhydrogen peroxide (H2O2) and to evaluate whether the hepatoprotective effect ofmonomers was independence or synergy in mice stimulated by carbon tetrachloride(CCl4). Monomers protected against oxidative stress in HepG2 cells in a doseresponsemanner by inhibiting the generation of reactive oxygen species, increasingtotal antioxidant capacity, catalase and superoxide dismutase (SOD) activities, andactivating the antioxidative pathway of nuclear factor E2-related factor 2/KelchlikeECH-associated protein 1 (Nrf2/Keap1) signaling pathway. We found that thein vitro antioxidant capacities of paeonol and quercetin were better than those of-sitosterol and gallic acid. Furthermore, paeonol apparently diminished the levelsof alanine transaminase and aspartate aminotransferase, augmented the contentsof glutathione and SOD, promoted the expressions of Nrf2 and heme oxygenase-1proteins in mice stimulated by CCl4. In HepG2 cells, paeonol, quercetin, -sitosterol,and gallic acid play a defensive role against H2O2-induced oxidative stress throughactivating Nrf2/Keap1 pathway, indicating that these monomers have anti-oxidativeproperties. Totally, paeonol and quercetin exerted anti-oxidative and hepatoprotectiveeffects, which is independent rather than synergy.