Inhibitory effect of astragalin on expression of lipopolysaccharide-induced inflammatory mediators through NF-κB in macrophages.
Astragalin (kaempferol-3-O-glucoside), a newly found flavonoid from leaves of persimmon or Rosa agrestis, is known to have antiatopic dermatitis and antioxidant activity. However, the effect of astragalin on the inflammatory response is not well defined. Nitric oxide (NO) produced from the activated macrophages is well known as a mediator of inflammation. Transcription factor (NF)-κB mediates the inducible expression of a variety of genes involved in immune and inflammatory responses including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and cytokines/chemokines. In the present study, we examined the inhibitory effects of astragalin on the lipopolysaccharide (LPS)-induced inflammatory mediators. Astragalin significantly reduced LPS-induced expression of iNOS, COX-2 and cytokines/chemokines, and production of NO in J774A.1 mouse macrophages. Astragalin inhibited LPSinduced activation of NF-κB as indicated by inhibition of degradation of IκBα, nuclear translocation of NF-κB, and NF-κB dependent gene reporter assay. The inhibitory effects of astragalin on the inflammatory mediators are comparable with quercetin, a well known flavonoid possessing antioxidant and anti-inflammatory activity. Using the mouse peritoneal macrophages, we confirmed the inhibitory effect of astragalin on NO production and NF-κB activation. Taken together, our results indicate that astragalin inhibits expression of proinflammatory mediators through the inhibition of NF-κB in macrophages.
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, 700-422, Korea.
Mi-Sun
MS
Kim
Sang-Hyun
SH
Kim
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism*; D044949:Kaempferols / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism
D018836:Inflammation Mediators; D044949:Kaempferols; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; C001579:astragalin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2