Inhibition of prostaglandin and nitric oxide production in lipopolysaccharide-treated RAW 264.7 cells by tanshinones from the roots of Salvia miltiorrhiza Bunge

초록

This study examnined the effects of tanshinone derivatives (tanshinone 1, cryptotanshinone, 15,16-dihydrotanshinone 1) on prostaglandin (PG) and nitric oxide (NO) metabolism in an attempt to establish their anti-inflammatory mechanisms and to present a scientific rationale for the use of Salvia miltiorrhiza (danshen) in inflammatory conditions. From lipopolysaccharide-treated RAW 264.7 cells, cyclooxygenase-2 (COX-2)-mediated PGE(2) production was inhibited by tanshinone 1, cryptotanshinone and 15,16-dihydrotanshinone 1, while only cryptotanshinone and 15,16-dihydrotanshinone I inhibited inducible NO synthase (iNOS)-mediated NO synthesis at 1-50 mu M. Particularly, cryptotanshinone was found to be a down-regulator of proinflammatory molecule expression, including COX-2 and NOS. The electrophoretic mobility shift assay showed that cryptotanshinone and 15,16-dihydrotanshinone I also inhibited the activation of the transcription factors, such as nuclear transcription factor-kappa B and activator protein-1. Moreover, cryptotanshinone exhibited in vivo anti-inflammatory activity against carrageenan-induced paw edema in rats. Overall, these results provide additional scientific rationale for the anti-inflammatory use of danshen in Chinese medicine. Especially, cryptotanshinone and 15,16-dihydrotanshinone I are important constituents.

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