wogonoside and Chemical-and-Drug-Induced-Liver-Injury

Wogonoside, a bioactive flavonoid extracted from the root of Scutellaria baicalensis Georgi, has been reported to have anti-inflammatory and antioxidant effects. In this study, we examined the protective effects of wogonoside against lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced liver injury in mice. Mice were given an intraperitoneal injection of wogonoside 1h before LPS and d-GalN treatment. The results showed that wogonoside inhibited the production of serum Alanine transaminase (ALT), Aspartate aminotransferase (AST), IL-1β, TNF-α, and hepatic malondialdehyde (MDA) content induced by LPS/GalN. In addition, wogonoside promoted the expression of Nrf2, NQO-1, GCLC, and HO-1. Wogonoside inhibited the expression of hepatic NLRP3, ASC, caspase-1, and IL-1β induced by LPS/GalN. In conclusion, these results suggest that wogonoside protects against LPS/GalN-induced acute liver injury by activating Nrf2 and inhibiting NLRP3 inflammasome activation.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cytoprotection; Flavanones; Galactosamine; Gene Expression Regulation, Enzymologic; Glucosides; Glutathione; Interleukin-1beta; Lipopolysaccharides; Liver; Male; Malondialdehyde; Mice; Mice, Inbred BALB C; NF-kappa B; Tumor Necrosis Factor-alpha

Wogonoside (WO), a flavonoid extracted from Huangqin, plays multiple physiological roles. However, it has remained elusive how WO regulates hepatic fibrogenesis until now.. The purpose of the study was to investigate the potential protective effects of WO against liver fibrosis induced by carbon tetrachloride (CCl4).. In this study, male rats were randomly allocated into four groups: a control group, the CCl4 group, the CCl4 and WO (4 mg/kg) group, and CCl4 and WO (8 mg/kg) group. Hepatic fibrosis was induced by subcutaneous injection of CCl4 twice a week for a continuous 6-week period. Then the rats were intragastrically administrated with WO daily for 4 weeks before being killed.. As expected, histopathological assessment, Masson trichrome staining, and Sirius red staining demonstrated that WO drastically ameliorated the hepatic fibrosis caused by CCl4. WO significantly attenuated the CCl4-induced upregulations of liver indices including alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin-1β, IL-6, hexadecenoic acid and laminin in serum, as well as hydroxyproline, malondialdehyde and phosphatidylinositol 3-kinase (PI3K)/protein Kinase B(Akt)/mechanistic target of rapamycin (mTOR)/nuclear factor-kappa B signalings in liver. Meanwhile, WO also effectively recovered the depletions of superoxide dismutase, glutathione and IL-10. Furthermore, we evaluated the effects of WO on the alpha smooth muscle actin, type I collagen expressions, and PI3K/Akt/ mTOR/ribosomal protein S6 kinase 70 kDa (p70S6K) signaling in transforming growth factor (TGF-β) stimulated hepatic stellate cell-T6 cells.. These results suggested that WO had significant protective effects against liver fibrosis induced by CCl4.

Topics: Animals; Biomarkers; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Collagen; Cytoprotection; Dose-Response Relationship, Drug; Flavanones; Glucosides; Inflammation Mediators; Intracellular Signaling Peptides and Proteins; Liver; Liver Cirrhosis, Experimental; Male; Oxidative Stress; Protective Agents; Rats, Wistar; Signal Transduction; Time Factors