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

Int Immunopharmacol. 2017 Sep:50:95-106. doi: 10.1016/j.intimp.2017.06.013. Epub 2017 Jun 21.

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-α and IL-6 in EtOH-induced RAW264.7 cells. Furthermore, our findings showed that wogonin remarkably induced the expression of PPAR-γ in vivo and in vitro. Compared with the wogonin-treated group, blockade of PPAR-γ with inhibitor (T0070907) or PPAR-γ 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-γ further suppressed the expression of TNF-α and IL-6 when treated with wogonin on EtOH-induced RAW264.7 cells. In addition, it was demonstrated that wogonin remarkably suppressed PPAR-γ-meditated phosphorylation and activation of NF-κB-P65. In conclusion, our results indicated that wogonin may serve as an effective modulator of PPAR-γ by down-regulating NF-κB pathway, thereby attenuated inflammatory response in ALD.

Keywords: Alcoholic liver disease (ALD); Inflammation; NF-κB; PPAR-γ; Wogonin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Benzamides / pharmacology
  • Disease Models, Animal
  • Ethanol / administration & dosage
  • Flavanones / therapeutic use*
  • Humans
  • Immunomodulation
  • Inflammation Mediators / metabolism
  • Interleukin-6 / metabolism
  • Liver Diseases, Alcoholic / drug therapy*
  • Liver Diseases, Alcoholic / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Pyridines / pharmacology
  • RAW 264.7 Cells
  • RNA, Small Interfering / genetics
  • Scutellaria baicalensis / immunology
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Benzamides
  • Flavanones
  • Inflammation Mediators
  • Interleukin-6
  • PPAR gamma
  • Pyridines
  • RNA, Small Interfering
  • Rela protein, mouse
  • T 0070907
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Ethanol
  • wogonin