LAUSR

Abstract 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‐&agr; and IL‐6 in EtOH‐induced RAW264.7 cells. Furthermore, our findings showed that wogonin remarkably induced the expression of PPAR‐&ggr; in vivo and in vitro. Compared with the wogonin‐treated group, blockade of PPAR‐&ggr; with inhibitor (T0070907) or PPAR‐&ggr; 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‐&ggr; further suppressed the expression of TNF‐&agr; and IL‐6 when treated with wogonin on EtOH‐induced RAW264.7 cells. In addition, it was demonstrated that wogonin remarkably suppressed PPAR‐&ggr;‐meditated phosphorylation and activation of NF‐&kgr;B‐P65. In conclusion, our results indicated that wogonin may serve as an effective modulator of PPAR‐&ggr; by down‐regulating NF‐&kgr;B pathway, thereby attenuated inflammatory response in ALD. HighlightsAnti‐inflammatory effects of wogonin in vivo and in vitroWogonin activates expression of PPAR‐&ggr; both in mice with alcoholic liver disease (ALD) and in EtOH‐induced RAW264.7 cells.The expression of NF‐&kgr;B‐P65 and NF‐&kgr;B‐p‐P65 are attenuated by up‐regulating PPAR‐&ggr;.