Active ingredients of traditional Japanese (kampo) medicine, inchinkoto, in murine concanavalin A-induced hepatitis

Active ingredients of traditional Japanese (kampo) medicine, inchinkoto, in murine concanavalin A-induced hepatitis
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DOI:
10.1016/j.jep.2009.11.029
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发表时间:
2010-02-17
影响因子:
5.4
通讯作者:
Hasegawa, Takaaki
Hasegawa, Takaaki
中科院分区:
医学2区
文献类型:
--
作者:
Mase, Akihito;Makino, Bunsho;Hasegawa, Takaaki

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研究目的:传统的日本(汉方)药物inchinkoto(ICKT)在东亚用作利胆和保肝药。以前,我们报道ICKT通过抑制干扰素(IFN)-γ和白细胞介素(IL)-12的产生来改善小鼠伴刀豆球蛋白A(con A)诱导的肝炎。本研究对ICKT的活性成分进行了研究。材料与方法:对ICKT及其组分中药提取物进行了分离,并对ICKT的抗肝损伤作用和细胞因子的产生进行了研究(肝损伤的生化标志物和血清中的细胞因子水平)和体外(脾细胞和腹腔巨噬细胞培养物中的细胞因子和亚硝酸盐产生)。口服给药组分草药,茵陈蒿(Artemisia capillaris Thunberg:'Inchinko'在日本),栀子(Gardenia jasminoides Ellis:'Sanshishi')和大黄(Rheum palmatum Linne:'Daio')。Inchinko和Sanshishi降低血清转氨酶和IFN-γ浓度。组分草药的馏分的检查表明,毛细血管,Inchinko的一个组成部分,在体内具有有效的肝保护活性。在体外研究中,检测了茵陈皂苷和京尼平,京尼平是三石石中含有的京尼平苷的肠道代谢产物。IFN-γ的产生显着抑制毛细血管和京尼平在Con A刺激的脾细胞培养。京尼平还抑制IL-1 β、IL-6和IL-12 p70的合成。Capillarisin和京尼平降低亚硝酸盐从IFN-γ刺激macrophages.Conclusions释放:这些结果表明,Inchinko和三石石可能有助于ICKT对Con A肝炎的保护作用。毛细血管肽被发现是有效的hepa保护,京尼平也可能有助于,特别是通过调节细胞因子的产生。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Aim of the study: The traditional Japanese (kampo) medicine inchinkoto (ICKT) is used in Eastern Asia as a choleretic and hepatoprotective agent. Previously, we reported that ICKT ameliorates murine concanavalin A (con A)-induced hepatitis via suppression of interferon (IFN)-gamma and interleukin (IL)-12 production. In the present study, we investigated the active ingredients of ICKT.Materials and methods: ICKT and extracts of its component herbs were fractionated, and their effects on liver injury and cytokine production in vivo (biochemical markers of liver injury and cytokine levels in serum) and in vitro (cytokine and nitrite production in the cultures of splenocytes and peritoneal macrophages).Results: Decoctions of component herbs, Artemisiae Capillari Spica (Artemisia capillaris Thunberg: 'Inchinko' in Japanese), Gardeniae Fructus (Gardenia jasminoides Ellis: 'Sanshishi') and Rhei Rhizoma (Rheum palmatum Linne: 'Daio') were administered orally. Inchinko and Sanshishi decreased serum transaminases and IFN-gamma concentrations. Examination of fractions of component herbs suggested that capillarisin, a component of Inchinko, has potent hepatoprotective activity in vivo. In in vitro studies, capillarisin and genipin, an intestinal metabolite of geniposide that is contained in Sanshishi, were examined. IFN-gamma production was significantly suppressed by capillarisin and genipin in con A-stimulated splenocyte culture. Genipin also suppressed IL-1 beta, IL-6, and IL-12p70 synthesis. Capillarisin and genipin decreased nitrite release from IFN-gamma-stimulated macrophages.Conclusions: These results suggested that both Inchinko and Sanshishi may contribute to the protective effects of ICKT against con A hepatitis. Capillarisin was found to be potently hepa to protective, and genipin may also contribute, especially via modulation of cytokine production. (C) 2009 Elsevier Ireland Ltd. All rights reserved.