Compound Astragalus and Salvia miltiorrhiza extract suppresses hepatocellular carcinoma progression by inhibiting fibrosis and PAI-1 mRNA transcription
Compound Astragalus and Salvia miltiorrhiza extract suppresses hepatocellular carcinoma progression by inhibiting fibrosis and PAI-1 mRNA transcription
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复方黄芪丹参提取物通过抑制纤维化和 PAI-1 mRNA 转录抑制肝细胞癌进展
DOI：
10.1016/j.jep.2013.10.022
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发表时间：
2014-01-10
影响因子：
5.4
通讯作者：
Yang, Yan
中科院分区：
文献类型：
--
作者：
Rui, Wenjuan;Xie, Lei;Yang, Yan
民族药理学相关性：黄芪和丹参在中国已被用于治疗肝脏疾病数百年。已有研究表明，这些中药及其提取物对肝纤维化的发展和人肝癌HepG 2细胞的增殖和侵袭有抑制作用。需要进一步研究它们对肝细胞癌（HCC）的药理作用。观察复方黄芪丹参提取物（CASE）对二乙基亚硝胺（DEN）诱发大鼠肝癌的影响。雄性大鼠分为5组，第1组为正常对照组，第2组每周5次给予0.2%DEN溶液，共14周，第3 ~ 5组分别给予DEN和CASE，剂量分别为60、120和240 mg/kg/d，连续16周。肝癌发病率，血清酶水平，纤维化程度和羟脯氨酸含量进行了评估和比较，在五组之间，以确定CASE的抑制纤维化和HCC进展。此外，在体外实验中使用HepG 2细胞进行，以验证CASE的纤溶酶原激活物抑制剂-1（派-1）mRNA.Results的转录的影响：CASE治疗显着降低DEN诱导的肝癌发展的发病率和多样性，以剂量依赖性的方式。能显著抑制DEN诱导的肝癌大鼠血清丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转移酶、碱性磷酸酶、透明质酸、直接胆红素和总胆红素的升高，显著减轻血清总蛋白的下降。CASE治疗还显著抑制了GST-P和α-SMA的表达升高。结论：CASE通过抑制肝纤维化和派-1 mRNA的转录，抑制DEN诱导的肝癌发生，具有潜在的临床应用价值。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Astragalus membranaceus and Salvia miltiorrhiza have been used for centuries in China to treat liver diseases. Previous studies have shown that these herbs and their extracts inhibit the development of liver fibrosis and the proliferation and invasion of human hepatoma HepG2 cells. Further study of their pharmacological effects on hepatocellular carcinoma (HCC) is needed. To investigate the effects of Compound Astragalus and Salvia miltiorrhiza Extract (CASE) on diethylinitrosamine (DEN)-induced hepatocarcinogenesis in rats.Materials and methods: Male rats were divided into five groups, with the first group serving as normal control, the second group receiving 0.2% DEN solution five times a week for 14 weeks, and the third to fifth group receiving the same DEN as in the second group together with CASE at the doses of 60,120, and 240 mg/kg per day for 16 weeks, respectively. Hepatoma incidence, serum enzymes levels, degree of fibrosis and hydroxyproline content were evaluated and compared across the five groups to determine CASE's suppression of fibrosis and HCC progression. In addition, an in vitro experiment using HepG2 cells was conduct to verify CASE's effect on the transcription of plasminogen activator inhibitor-1 (PAI-1) mRNA.Results: CASE treatment significantly reduced the incidence and multiplicity of DEN-induced HCC development in a dose-dependent manner. It significantly suppressed the elevation of alanine transaminase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, hyaluronic acid, direct bilirubin and total bilirubin, and significantly lessened the depression of serum total protein in DEN-induced HCC rats. CASE treatment also significantly suppressed the elevated expression of GST-P and alpha-SMA. The in vitro experiment confirmed that CASE inhibits the transcription of PAI-1 mRNA in HepG2 cells induced by TGF-beta(1) in a dose-dependent manner.Conclusions: CASE suppresses DEN-induced hepatocarcinogenesis by inhibiting fibrosis and PAI-1 mRNA transcription, suggesting its potential clinical application in preventing and treating human HCC. (C) 2013 Elsevier Ireland Ltd. All rights reserved.