Isovitexin suppresses lipopolysaccharide-mediated inducible nitric oxide synthase through inhibition of NF-kappa B in mouse macrophages.
Isovitexin exhibits potent antioxidant activities. In this study, the activity of nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated RAW264.7 macrophages after incubation with isovitexin was investigated. Isovitexin was able to reduce the production of hydrogen peroxide induced by LPS in mouse macrophage RAW264.7 cells. The cells incubated with isovitexin had markedly reduced LPS-stimulated NO production with an IC (50) value of 58.5 microM. The expression of iNOS was also inhibited when the cells were treated with isovitexin. A transient transfection experiment showed that isovitexin suppressed the iNOS promoter and NF-kappaB-dependent transcriptional activities. It was also found to inhibit IKK kinase activity and prevent the degradation of IkappaBalpha in activated RAW264.7 cells. Additionally, Western blotting analysis revealed that isovitexin prevented the translocation of NF-kappaB from the cytoplasm to the nucleus. Our results indicate that its ROS scavenger and IKK inhibitory activities also contribute to the suppression of ROS-mediated NF-kappaB activity. These results suggest that isovitexin, a food phytochemical contained in dietary rice products, might have biological significance.
Lin
Chun-Mao
CM
College of Medicine, Taipei Medical University, Taipei, Taiwan. cmlin@tmu.edu.tw
Huang
Sheng-Tung
ST
Liang
Yu-Chih
YC
Lin
Mei-Shan
MS
Shih
Chwen-Ming
CM
Chang
Yuan-Ching
YC
Chen
Tzong-Yueh
TY
Chen
Chien-Tsu
CT
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D047310:Apigenin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005434:Flow Cytometry; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012275:Oryza; D008517:Phytotherapy; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000975:Antioxidants; D017931:DNA Primers; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047310:Apigenin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C049772:isovitexin