Broussochalcone A, a potent antioxidant and effective suppressor of inducible nitric oxide synthase in lipopolysaccharide-activated macrophages

The antioxidant properties of broussochalcone A (BCA) and its effects on ni tric oxide (NO)production in lipopolysaccharide (LPS)-activated macrophages were investigated in this study. BCA, isolated from Broussonetia papyrifer a Vent., inhibited iron-induced lipid peroxidation in rat brain homogenate in a concentration-dependent manner with an IC50 of 0.63 +/- 0.03 muM. It w as as potent as butylated hydroxytoluene, a common antioxidant used for foo d preservation. In a diphenyl-2-picrylhydrazyl assay system, the radical-sc avenging activity of BCA seemed to be more potent than that of alpha -tocop herol, its IC0.200 being 7.6 +/- 0.8 muM. BCA could directly scavenge super oxide anion and hydroxyl radicals. These results indicated that BCA was a p owerful antioxidant with versatile free radical-scavenging activity. On the other hand, we found that BCA suppressed NO production concentration-depen dently, with an IC50 of 11.3 muM in LPS-activated macrophages. This effect was not the consequence of a direct inhibitory action on the enzyme activit y of inducible NO synthase (iNOS). Our results indicated that BCA exerts po tent inhibitory effects on NO production, apparently mediated by its suppre ssion of I kappaB alpha phosphorylation, I kappaB alpha degradation, nuclea r factor-kappa B activation, and iNOS expression. Therefore, we conclude th at the antioxidant activities of BCA and its inhibition of I kappaB alpha d egradation and iNOS protein expression may have therapeutic potential, give n that excessive free radicals and NO production have been associated with various inflammatory diseases. (C) 2001 Elsevier Science Inc. All rights re served.