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: Ming Ye, Qing Wang, Weifeng Zhang, Zhiyu Li, Yajing Wang, Rong Hu
• Journal: Biochemistry and cell biology = Biochimie et biologie cellulaire (Biochem Cell Biol) Vol. 92 Issue 5 Pg. 337-48 (Oct 2014) ISSN: 1208-6002 [Electronic] Canada
• PMID: 25247252 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Flavonoids
• Lipopolysaccharides
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one
• Nitric Oxide Synthase Type II
• Heme Oxygenase-1
• Cyclooxygenase 2
• NAD(P)H Dehydrogenase (Quinone)
• Nqo1 protein, mouse
• Proteasome Endopeptidase Complex

Topics

• Active Transport, Cell Nucleus
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Cell Line
• Cell Nucleus (metabolism)
• Cell Survival (drug effects)
• Cyclooxygenase 2 (genetics)
• Flavonoids (pharmacology)
• Heme Oxygenase-1 (metabolism)
• Inflammation (immunology, metabolism)
• Lipopolysaccharides (immunology)
• Macrophages (drug effects, immunology, metabolism)
• Mice
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• NF-E2-Related Factor 2 (genetics, metabolism)
• Nitric Oxide Synthase Type II (genetics)
• Proteasome Endopeptidase Complex (drug effects)
• Signal Transduction (drug effects)
• Transcriptional Activation
• Ubiquitination (drug effects)