title: Broussochalcone A, a potent antioxidant and effective suppressor of inducible nitric oxide synthase in lipopolysaccharide-activated macrophages.
abstract: The antioxidant properties of broussochalcone A (BCA) and its effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages were investigated in this study. BCA, isolated from Broussonetia papyrifera Vent., inhibited iron-induced lipid peroxidation in rat brain homogenate in a concentration-dependent manner with an IC(50) of 0.63 +/- 0.03 microM. It was as potent as butylated hydroxytoluene, a common antioxidant used for food preservation. In a diphenyl-2-picrylhydrazyl assay system, the radical-scavenging activity of BCA seemed to be more potent than that of alpha-tocopherol, its IC(0.200) being 7.6 +/- 0.8 microM. BCA could directly scavenge superoxide anion and hydroxyl radicals. These results indicated that BCA was a powerful antioxidant with versatile free radical-scavenging activity. On the other hand, we found that BCA suppressed NO production concentration-dependently, with an IC(50) of 11.3 microM in LPS-activated macrophages. This effect was not the consequence of a direct inhibitory action on the enzyme activity of inducible NO synthase (iNOS). Our results indicated that BCA exerts potent inhibitory effects on NO production, apparently mediated by its suppression of IkappaBalpha phosphorylation, IkappaBalpha degradation, nuclear factor-kappa B activation, and iNOS expression. Therefore, we conclude that the antioxidant activities of BCA and its inhibition of IkappaBalpha degradation and iNOS protein expression may have therapeutic potential, given that excessive free radicals and NO production have been associated with various inflammatory diseases.
authors: Pharmacological Institute, College of Medicine, National Taiwan University, No. 1, Jen-Ai Rd., Sect. 1, Taipei, Taiwan.
authors: Z
authors: Z
authors: Cheng
authors: C
authors: C
authors: Lin
authors: T
authors: T
authors: Hwang
authors: C
authors: C
authors: Teng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015764:Bepridil / Q000031:analogs & derivatives* / Q000378:metabolism; D001713:Biphenyl Compounds; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D055511:CCN Intercellular Signaling Proteins; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047188:Chalcones; D004268:DNA-Binding Proteins / Q000378:metabolism; D004794:Enzyme Repression; D006133:Growth Substances; D017665:Hydroxyl Radical / Q000378:metabolism; D020672:I-kappa B Proteins; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D015513:Oncogene Proteins; D010851:Picrates; D011518:Proto-Oncogene Proteins; D051381:Rats; D012118:Resorcinols / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D055511:CCN Intercellular Signaling Proteins; C492067:CCN4 protein, mouse; C492066:CCN4 protein, rat; D047188:Chalcones; D004268:DNA-Binding Proteins; D006133:Growth Substances; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D015513:Oncogene Proteins; D010851:Picrates; D011518:Proto-Oncogene Proteins; D012118:Resorcinols; D013481:Superoxides; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D002599:Chalcone; D015764:Bepridil; C106525:broussochalcone A; C004931:1,1-diphenyl-2-picrylhydrazyl; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat