A Mixture of Fermented Schizandrae Fructus Pomace and Hoveniae Semen cum Fructus Extracts Synergistically Protects against Oxidative Stress-Mediated Liver Injury

Schizandrae Fructus (SF) and Hoveniae Semen cum Fructus (HSCF) have long been used as medicinal herbs for treating various diseases in Asian traditional medicine. In the current study, we investigated the protective effect of fermented SF pomace and HSCF extract 1:1 (w:w) combination mixture (MSH) against carbon tetrachloride (CCl4)-induced acute liver injury mice. After MSH (50-200 mg/kg) oral administration for 7 consecutive days, animals were injected intraperitoneally with CCl4 (0.5 mL/kg). Histopathological observation revealed that administration of MSH synergistically decreased the degeneration of hepatocytes and the infiltration of inflammatory cells induced by CCl4. Moreover, MSH administration reduced the activities of alanine aminotransferase, aspartate aminotransferase, and ?-glutamyl transpeptidase in serum, and mitigated apoptotic cell death in hepatic parenchyma. In addition, MSH alleviated CCl4-mediated lipid peroxidation by restoring endogenous antioxidants capacities including glutathione contents, superoxide dismutase, and catalase activities. In vitro assessments using tert-butyl hydroperoxide-induced oxidative stress in HepG2 cells revealed that MSH protects hepatocytes by lowering ROS generation and lipid peroxidation via upregulating the transcriptional activity of nuclear factor erythroid-2-related factor 2 and the expression of antioxidant genes. Furthermore, MSH synergistically attenuated the expression of proinflammatory cytokines in CCl4-injured liver and lipopolysaccharide-stimulated RAW 264.7 cells. Taken together, these findings suggest that MSH has the potential to prevent acute liver damage by effectively suppressing oxidative stress and inflammation.