Protective Effect of Scutellariae Radix Flavonoids in Drug-Induced Liver Injury---A Novel Target of IL-17

IL-17 is the major cytokine of Th17 lymphocytes and has been found to be present at the inflammatory site in several human inflammatory and autoimmune diseases. Recent studies show that the Th17 cell and its related cytokine IL-17 has involvement of different liver disorders in both mice models and human studies. Our preliminary data also show that drug-induced acute hepatotoxicity is markly decrease in the IL-17 knockout mice. However, the role of IL-17 in drug-induced liver injury is still unclear. In this study, we will first establish acetaminophen-induced hepatotoxicity in vivo and ex vivo models for further understanding of IL-17 mechanisms in drug-induced liver injury. Scutellariae radix is a traditional herbal medicine and from the root of the medicinal plant scutellaria. Scutellariae radix flavonoids have been shown to possess antiinflammatory, antiviral, anticancer, and antioxidant effects. Recent studies have shown that scutellariae radix flavonoids have hepatoprotective effect in viral hepatitis and alcoholic liver damage. In our primary data showed that two major Scutellariae radix flavonoids (wogonin and baicalin) could attenuate hepatic damage and prevent hepatic IL-17 elevation in acetaminophen-induced liver injury. However, the effect of Scutellariae radix flavonoids in drug-induced liver injury is not yet elucidated. Whether IL-17 plays a key role in scutellariae radix flavonoids-related hepatoprotective function is unknown. In this study, we will systemic exam the hepatoprotective effect of scutellariae radix flavonoids in mice models of acute drug-induced liver injury and further investigate the mechanism and signaling pathway of IL-17 in hepatoprotective effects of scutellariae radix flavonoids. Neutrophils have been thought as important contributors to the drug-induced inflammation and tissue damage. Recenty reports show that IL-17 can induce many inflammatory cytokines and effect neutrophil infiltration and activation. Our preliminary data showed that the hepatic neutrophils and neutrophil-related cytokines are decrease in IL-17 knockout mice in acetaminophen-induced liver injury. However, the mechanism of neutrophil recruitment in drug-induced injury liver is still not clear. Therefore, further studies are necessary to elucidate the role of IL-17 on neutrophils in drug-induced liver injury. In this research, we will systemic evaluate the hepatoprotective effects and mechanisms of scutellariae radix flavonoids in IL-17 as a target, as well as for the new development of prevention and treatment in drug-induced liver injury.

Project ID:PC10401-0617
External Project ID:MOST103-2314-B182-046-MY2