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Heme oxygenase-1 mediates the inhibitory actions of brazilin in RAW264.7 macrophages stimulated with lipopolysaccharide

Hu, Chien-Ming, Liu, Yung-Hung, Cheah, Khoot-Peng, Li, Joe-Sharg, Lam, Carlos-Shu Kei, Yu, Wen-Yu, Choy, Cheuk-Sing
Journal of ethnopharmacology 2009 v.121 no.1 pp. 79-85
Oriental traditional medicine, Caesalpinia sappan, chemical constituents of plants, medicinal plants, anti-inflammatory activity, macrophages, lipopolysaccharides, heme oxygenase (decyclizing), cytotoxicity, protein synthesis, dose response, messenger RNA, enzyme activity, nitric oxide, prostaglandins, interleukin-1, tumor necrosis factor-alpha, nitric oxide synthase, protoporphyrin
Brazilin, the main constituent of Caesalpinia sappan L., is a natural red pigment that has been reported to possess anti-inflammatory properties. This study aimed to identify a novel anti-inflammatory mechanism of brazilin. We found that brazilin did not cause cytotoxicity below 300μM, and activated heme oxygenase-1 (HO-1) protein synthesis in a concentration-dependent manner at 10-300μM in RAW264.7 macrophages without affecting mRNA transcription of HO-1. Additionally, brazilin increased bilirubin production and HO-1 activity in RAW264.7 macrophages. In lipopolysaccharide (LPS)-stimulated macrophages, brazilin suppressed the release of nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin (IL)-1β and tumor necrosis factor-α (TNF-α), and reduced the expression of inducible nitric oxide synthase (iNOS). A specific inhibitor of HO-1, Zn(II) protoporphyrin IX, blocked the suppression of NO production, cytokines release and iNOS expression by brazilin. These results suggest that brazilin possesses anti-inflammatory actions in macrophages and works through a novel mechanism involving the action of HO-1.