Four active monomers from Moutan Cortex exert inhibitory effects against oxidative stress by activating Nrf2/Keap1...

Paeonol, quercetin, β-sitosterol, and gallic acid extracted from Moutan Cortex had been reported to possess anti-oxidative, anti-inflammatory, and antitumor activities. This work aimed to illustrate the potential anti-oxidative mechanism of monomers in human liver hepatocellular carcinoma (HepG2) cells-induced by hydrogen peroxide (H₂O₂) and to evaluate whether the hepatoprotective effect of monomers was independence or synergy in mice stimulated by carbon tetrachloride (CCl₄). Monomers protected against oxidative stress in HepG2 cells in a doseresponse manner by inhibiting the generation of reactive oxygen species, increasing total antioxidant capacity, catalase and superoxide dismutase (SOD) activities, and activating the antioxidative pathway of nuclear factor E2-related factor 2/Kelchlike ECH-associated protein 1 (Nrf2/Keap1) signaling pathway. We found that the in vitro antioxidant capacities of paeonol and quercetin were better than those of β-sitosterol and gallic acid. Furthermore, paeonol apparently diminished the levels of alanine transaminase and aspartate aminotransferase, augmented the contents of glutathione and SOD, promoted the expressions of Nrf2 and heme oxygenase-1 proteins in mice stimulated by CCl₄. In HepG2 cells, paeonol, quercetin, β-sitosterol, and gallic acid play a defensive role against H₂O₂-induced oxidative stress through activating Nrf2/Keap1 pathway, indicating that these monomers have anti-oxidative properties. Totally, paeonol and quercetin exerted anti-oxidative and hepatoprotective effects, which is independent rather than synergy.