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6354725 
Journal Article 
Anti-inflammatory mechanism of galangin in lipopolysaccharide-stimulated microglia: Critical role of PPAR-? signaling pathway 
Choi, MJ; Lee, EJ; Park, JS; Kim, SN; Park, EM; Kim, HS 
2017 
Yes 
Biochemical Pharmacology
ISSN: 0006-2952
EISSN: 1873-2968 
144 (November 15 
120-131 
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)-?B 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)-?, 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-? was involved in the anti-inflammatory function of galangin. Pretreatment with a PPAR-? antagonist or siRNA significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-a, nitric oxide (NO), and IL-6 in LPS-stimulated microglia. Moreover, the PPAR-? antagonist reversed the effects of galangin on NF-?B, Nrf2, and CREB. Altogether, our data suggest that PPAR-? plays a key role in mediating the anti-inflammatory effects of galangin by modulating the NF-?B and Nrf2/CREB signaling pathways. 
Animals; Anti-Inflammatory Agents/pharmacology; Cell Line; Transformed; Dose-Response Relationship; Flavonoids/pharmacology; Inflammation Mediators/antagonists & inhibitors; Inflammation Mediators/metabolism; Lipopolysaccharides/toxicity; Inbred ICR; Microglia/drug effects; Microglia/metabolism; PPAR gamma/physiology; Signal Transduction/drug effects; Signal Transduction/physiology; Index Medicus/