Inhibitory effects of Japanese herbal medicines sho-saiko-to and juzen-taiho-to on nonalcoholic steatohepatitis in mice.

Inhibitory effects of Japanese herbal medicines sho-saiko-to and juzen-taiho-to on nonalcoholic steatohepatitis in mice.
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DOI:
10.1371/journal.pone.0087279
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Fukusato T
Fukusato T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Takahashi Y;Soejima Y;Kumagai A;Watanabe M;Uozaki H;Fukusato T

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虽然日本草药(JHM)在日本被广泛使用,但只有少数研究调查了它们对非酒精性脂肪性肝炎(NASH)的影响。在本研究中,我们检测了4种JHM[Sho-Saiko-to(TJ-9)、inchin-Ko-to(TJ-135)、juzen-taiho-to(TJ-48)和Keishi-bukuryo-gan(TJ-25)]对NASH小鼠模型的影响。将DB/db小鼠随机分为6组:对照组(对照组)、蛋氨酸胆碱缺乏组(MCD)和添加TJ-9、TJ-135、TJ-48和TJ-25的MCD组(分别为TJ-9、TJ-135、TJ-48和TJ-25)。治疗4周后处死所有小鼠,进行生化、病理和分子分析。与MCD组相比,TJ-9和TJ-48组的血清丙氨酸氨基转移酶水平和肝组织学包括坏死性炎症和纤维化明显减轻。TJ-48可显著抑制肝组织转化生长因子-β1m RNA的表达。TJ-9和/或TJ-48组肿瘤坏死因子-α和白介素6的表达水平低于MCD组,而过氧化体增殖物激活受体γ的表达水平高于MCD组,差异无统计学意义。同样,即使结果没有统计学意义,TJ-9和TJ-48组肝组织中的丙二醛水平也低于MCD组。我们发现,JHMS,特别是TJ-9和TJ-48,可以抑制NASH小鼠模型肝脏的坏死性炎症和纤维化,尽管其机制尚未完全阐明。这些药物在NASH治疗中的临床应用的可能性还有待于进一步的研究。
Although Japanese herbal medicines (JHMs) are widely used in Japan, only a few studies have investigated their effects on nonalcoholic steatohepatitis (NASH). In the present study, we examined the effect of 4 kinds of JHMs [sho-saiko-to (TJ-9), inchin-ko-to (TJ-135), juzen-taiho-to (TJ-48), and keishi-bukuryo-gan (TJ-25)] on a mouse model of NASH. Db/db mice were divided into 6 groups: control diet (control), methionine- and choline-deficient diet (MCD), and MCD diet supplemented with TJ-9, TJ-135, TJ-48, and TJ-25 (TJ-9, TJ-135, TJ-48, and TJ-25, respectively). All mice were sacrificed after 4 weeks of treatment, and biochemical, pathological, and molecular analyses were performed. Serum alanine aminotransferase levels and liver histology, including necroinflammation and fibrosis, were significantly alleviated in the TJ-9 and TJ-48 groups compared with the MCD group. The expression level of transforming growth factor (TGF)-β1 mRNA in the liver was significantly suppressed by TJ-48. Although the differences were not statistically significant, the expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were lower, and those of peroxisome proliferators-activated receptor (PPAR)γ were higher in the TJ-9 and/or TJ-48 groups than in the MCD group. Similarly, even though the results were not statistically significant, malondialdehyde levels in liver tissues were lower in the TJ-9 and TJ-48 groups than in the MCD group. We showed that JHMs, especially TJ-9 and TJ-48, inhibited the necroinflammation and fibrosis in the liver of a mouse model of NASH, even though the mechanisms were not fully elucidated. Further studies are needed in the future to investigate the possibility of clinical application of these medicines in the treatment for NASH.
长期服用黄芩苷可改善高脂饮食大鼠的代谢紊乱和肝脂肪变性
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