Suppression of inducible nitric oxide synthase by (-)-isoeleutherin from the bulbs of Eleutherine americana through the regulation of NF-κB activity

초록

Eleutherine americana Merr. et Heyne (Iridaceae) has been used as a folk medicine for the treatment of coronary disorders and wound-healing. In our previous phytochemical study, several pyranonaphthoquinoids, including (-)-isoeleutherin, were isolated from the bulbs of E. americana. Because inhibitors of inducible nitric oxide synthase (iNOS) might be useful as anti-inflammatory agents, we investigated the potential of pyranonaphthoquinoids to inhibit iNOS activity. We found that (-)-isoeleutherin inhibits lipopolysaccharide (LPS)-stimulated induction of nitric oxide (NO) in a dose-dependent manner (IC50=7.4 mu M). Using western blots and reverse transcription-polymerase chain reaction, we showed that (-)-isoeleutherin suppresses the expression of iNOS protein and mRNA. In addition. (-)-isoeleutherin inhibited the expression of various cytokines such as interleukin-1 beta and interferon-beta. Activation of the transcriptional activity of NF-kappa B by LPS was also inhibited by treatment with (-)-isoeleutherin, suggesting that (-)-isoeleutherin-mediated suppression of iNOS expression is associated with the regulation of transcription factor NF-kappa B. These findings suggest that (-)-isoeleutherin might be a novel anti-inflammatory agent, and that it may work by inhibiting NF kappa B activation in macrophages. (C) 2008 Elsevier B.V. All rights reserved.

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