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http://dx.doi.org/10.4162/nrp.2016.10.3.251

Anti-inflammatory effects of proanthocyanidin-rich red rice extract via suppression of MAPK, AP-1 and NF-κB pathways in Raw 264.7 macrophages  

Limtrakul, Pornngarm (Department of Biochemistry, Faculty of Medicine, Chiang Mai University)
Yodkeeree, Supachai (Department of Biochemistry, Faculty of Medicine, Chiang Mai University)
Pitchakarn, Pornsiri (Department of Biochemistry, Faculty of Medicine, Chiang Mai University)
Punfa, Wanisa (Department of Biochemistry, Faculty of Medicine, Chiang Mai University)
Publication Information
Nutrition Research and Practice / v.10, no.3, 2016 , pp. 251-258 More about this Journal
Abstract
BACKGROUND/OBJECTIVES: Several pharmacological properties of red rice extract have been reported including anti-oxidant, anti-tumor, and reduced cancer cell invasion. This study was conducted to evaluate the anti-inflammatory effects of red rice extract on the production of inflammatory mediators in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages. MATERIALS/METHODS: Pro-inflammatory cytokines including tumor necrosis factor-${\alpha}$ and interleukin-6 were determined by ELISA and cyclooxygenase-2 and inducible nitric oxide synthase expression was evaluated using western blot analysis. In addition, the signaling pathway controlling the inflammatory cascade such as nuclear factor kappa B ($NF-{\kappa}B$), activator proteins-1 (AP-1), and mitogen-activated protein kinase (MAPK) was determined. RESULTS: Our results showed that red rice polar extract fraction (RR-P), but not non-polar extract fraction, inhibited interleukin-6, tumor necrosis factor-${\alpha}$, and nitric oxide production in LPS-induced Raw 264.7 cells. RR-P also reduced the expression of inflammatory enzymes, inducible nitric oxide synthase, and cyclooxygenase-2. In addition, activation of AP-1 and $NF-{\kappa}B$ transcription factor in the nucleus was abrogated by RR-P. RR-P inhibited the phosphorylation of extracellular signaling-regulated kinase 1/2, c-Jun NH2-terminal kinase, and p38 MAPK signaling responsible for the expression of inflammatory mediators in LPS-stimulated Raw 264.7 cells. Based on chemical analysis, high amounts of proanthocyanidin and catechins were detected in the RR-P fraction. However, only proanthocyanidin reduced $NF-{\kappa}B$ and AP-1 activation in LPS-activated Raw 264.7 cells. CONCLUSION: These observations suggest that the anti-inflammatory properties of RR-P may stem from the inhibition of pro-inflammatory mediators via suppression of the AP-1, $NF-{\kappa}B$, and MAPKs pathways.
Keywords
Cytokines; inflammation; lipopolysaccharide; phenolic; proanthocyanidin;
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