Anti-inflammatory mechanism of galangin in lipopolysaccharide-stimulated microglia: Critical role of PPAR-γ signaling pathway

Biochem Pharmacol. 2017 Nov 15:144:120-131. doi: 10.1016/j.bcp.2017.07.021. Epub 2017 Jul 28.


Since microglia-associated neuroinflammation plays a pivotal role in the progression of neurodegenerative diseases, controlling microglial activation has been suggested as a potential therapeutic strategy. Here, we investigated the anti-inflammatory effects of galangin (3,5,7-trihydroxyflavone) in microglia and analyzed the underlying molecular mechanisms. Galangin inhibited the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines and enhanced the expression of anti-inflammatory interleukin (IL)-10 in lipopolysaccharide (LPS)-stimulated BV2 microglia. Galangin also suppressed microglial activation and the expression of pro-inflammatory markers in LPS-injected mouse brains. The results of mechanistic studies have shown that galangin inhibited LPS-induced phosphorylation of p38 mitogen activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor (NF)-κB activity. On the contrary, galangin increased the activity of transcription factors, such as nuclear factor-E2-related factor 2 (Nrf2), cAMP response element-binding protein (CREB), and peroxisome proliferator-activated receptor (PPAR)-γ, known to play an anti-inflammatory role. In addition, galangin showed antioxidant effects by suppressing the expression of NADPH oxidase subunits p47phox and gp91phox, and by enhancing hemeoxygenase-1. We then investigated whether PPAR-γ was involved in the anti-inflammatory function of galangin. Pretreatment with a PPAR-γ antagonist or siRNA significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-α, nitric oxide (NO), and IL-6 in LPS-stimulated microglia. Moreover, the PPAR-γ antagonist reversed the effects of galangin on NF-κB, Nrf2, and CREB. Altogether, our data suggest that PPAR-γ plays a key role in mediating the anti-inflammatory effects of galangin by modulating the NF-κB and Nrf2/CREB signaling pathways.

Keywords: 3,3′-Diaminobenzidine tetrahydrochloride (PubChem CID: 23892); Avertin (PubChem CID: 6400); DMSO (PubChem CID: 679); Galangin; Galangin (PubChem CID: 5281616); H(2)DCFDA (PubChem CID: 77718); Lipopolysaccharide (PubChem CID: 53481793); NF-κB; Neuroinflammation; Nrf2/CREB signaling; PPAR-γ; Paraformaldehyde (PubChem CID: 712); Sodium deoxycholate (PubChem CID: 23668196); T0070907 (PubChem CID: 2777391); Triton X-100 (PubChem CID: 5590).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line, Transformed
  • Dose-Response Relationship, Drug
  • Flavonoids / pharmacology*
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / metabolism*
  • Lipopolysaccharides / toxicity*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Microglia / drug effects
  • Microglia / metabolism*
  • PPAR gamma / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Anti-Inflammatory Agents
  • Flavonoids
  • Inflammation Mediators
  • Lipopolysaccharides
  • PPAR gamma
  • galangin