title: Oroxylin A exerts anti-inflammatory activity on lipopolysaccharide-induced mouse macrophage via Nrf2/ARE activation.
abstract: Regulating inflammation could be an important measure for the effective treatment of cancer. Here we examine the mechanisms by which oroxylin A inhibits inflammation in RAW264.7 cells. The results demonstrate that pretreatment with oroxylin A (50, 100, and 150 μmol/L) inhibited lipopolysaccharide (LPS)-induced mRNA and protein expression of COX-2 and iNOS. In addition, oroxylin A significantly increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and NADP(H):quinone oxidoreductase (NQO1), induced Nrf2 translocation to the nucleus and up-regulated antioxidant response element (ARE)-luciferase reporter activity. Moreover, oroxylin A inhibited Nrf2 ubiquitination and proteasome activity. Transfection with Nrf2 siRNA knocked down Nrf2 expression and partially reversed oroxylin A-mediated inhibition of LPS-induced COX-2 and iNOS expression. Importantly, we showed for the first time that Nrf2 plays an important role in oroxylin A-suppressed inflammation in RAW264.7 cells. Uncovering the effect of oroxylin A on the regulation of Nrf2 signaling may be beneficial for developing new therapeutic strategies against inflammatory diseases.
authors.affiliation: a State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, 24 Tongjia Xiang, Jiangsu 210009, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ye
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Li
authors.forename: Yajing
authors.initials: Y
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D046988:Proteasome Endopeptidase Complex
keywords: inflammation; lipopolysaccharide (LPS); macrophages; nuclear factor erythroid 2-related factor 2 (Nrf2); oroxylin A; oroxyline A