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    Inhibitory effects of phloroglucinol derivatives from Mallotus japonicus on nitric oxide production by a murine macrophage-like cell line, RAW 264.7, activated by lipopolysaccharide and interferon-γ

    机译:延胡索中间苯三酚衍生物对脂多糖和γ-干扰素激活的小鼠巨噬细胞样细胞系RAW 264.7产生的一氧化氮的抑制作用

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    An aqueous acetone extract of the pericarps of Mallotus japonicus (MJE) inhibited nitric oxide (NO) production by a murine macrophage-like cell line, RAW 264.7, which was activated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Seven phloroglucinol derivatives isolated from MJE exhibited inhibitory activity against NO production. Among these phloroglucinol derivatives, isomallotochromanol exhibited strong inhibitory activity toward NO production, exhibiting an IC_(50) of 10.7 μM. MJE and the phloroglucinol derivatives significantly reduced both the induction of inducible nitric oxide synthase (iNOS) protein and iNOS mRNA expression. NO production by macrophages preactivated with LPS and IFN-γ for 16 h was also inhibited by MJE and the phloroglucinol derivatives. Furthermore, MJE and the derivatives directly affected the conversion of L-[~(14)C]arginine to L-[~(14)C]citrulline by the cell extract. These results suggest that MJE and the phloroglucinol derivatives have the pharmacological ability to suppress NO production by activated macrophages. They inhibited NO production by two mechanisms: reduction of iNOS protein induction and inhibition of enzyme activity.
    机译:刺槐(MJE)的果皮的丙酮水溶液提取物抑制了鼠巨噬细胞样细胞系RAW 264.7产生的一氧化氮(NO),该细胞系被脂多糖(LPS)和干扰素-γ(IFN-γ)激活。从MJE中分离出的七种间苯三酚衍生物对NO的产生具有抑制活性。在这些间苯三酚衍生物中,异麦角苯二酚对NO的产生具有较强的抑制活性,IC_(50)为10.7μM。 MJE和间苯三酚衍生物显着降低诱导型一氧化氮合酶(iNOS)蛋白和iNOS mRNA表达的诱导。 MJE和间苯三酚衍生物也抑制了用LPS和IFN-γ预活化16小时的巨噬细胞的NO产生。此外,MJE及其衍生物直接影响细胞提取物将L- [?(14)C]精氨酸转化为L- [?(14)C]瓜氨酸。这些结果表明,MJE和间苯三酚衍生物具有抑制活化的巨噬细胞产生NO的药理能力。他们通过两种机制抑制NO生成:iNOS蛋白诱导的减少和酶活性的抑制。

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