Wogonin attenuates inflammation by activating PPAR-γ in alcoholic liver disease

Alcoholic liver disease (ALD) is one of the predominant causes of liver-related morbidity and mortality worldwide. However, effective therapy for ALD is still lacking. Wogonin, a major flavonoid compound, is found in Scutellaria baicalensis Georgi. Accumulating studies have revealed that wogonin possesses anti-inflammatory and anti-tumour activities in various models. However, the hepatoprotective activity of wogonin in ALD is still obscure. In this study, we found that wogonin significantly attenuated inflammatory response in EtOH-fed mice, and reduced the expression of inflammatory cytokines such as TNF-alpha and IL-6 in EtOH-induced RAW264.7 cells. Furthermore, our findings showed that wogonin remarkably induced the expression of PPAR-gamma in vivo and in vitro. Compared with the wogonin-treated group, blockade of PPAR-gamma with inhibitor (T0070907) or PPAR-gamma small interfering (si)-RNA were applied in RAW264.7 cells to evaluate the involvement of wogonin in alleviating EtOH-induced inflammation. Moreover, forced expression of PPAR-gamma further suppressed the expression of TNF-alpha and IL-6 when treated with wogonin on EtOH-induced RAW264.7 cells. In addition, it was demonstrated that wogonin remarkably suppressed PPAR-gamma-meditated phosphorylation and activation of NF-kappa B-P65. In conclusion, our results indicated that wogonin may serve as an effective modulator of PPAR-gamma by down-regulating NF-kappa B, pathway, thereby attenuated inflammatory response in ALD.