Lee Tzung-Yan, Chang Hen-Hong, Chen Jenn-Han, Hsueh Ming-Lung, Kuo Jong-Jen
Graduate Institute of Traditional Chinese Medicine, Chang Gung University, Tao-Yuan, Taiwan, ROC.
J Ethnopharmacol. 2007 Jan 19;109(2):318-24. doi: 10.1016/j.jep.2006.07.042. Epub 2006 Aug 5.
The accumulation of hydrophilic bile acids in the liver is considered to play a pivotal role in the induction of hepatic injury. Yin-Chen-Hao-Tang (YCHT) decoction is an aqueous extract from three different herbs: Artemisia capillaries Thunb (Compositae), Gardenia jasminoides Ellis (Rubiaceae), Rheum officinale Baill (Polygonaceae), which has been recognized as a hepatoprotective agent for various types of liver diseases. Therefore, we used an experimental of biliary atresia model to test that YCHT plays a regulatory role in the pathogenesis of hepatic fibrosis. Hepatic damage with fibrosis was produced by common bile duct ligation (BDL) for 27 days in experimental cholestasis animal model. After surgery, YCHT (250 and 500mg/kg BW) oral administration once a day continued for 27 days. BDL caused a prominent liver collagen deposition that was supported by the increased alpha-SMA protein and mRNA expression of procollagen I. YCHT significantly decreased hepatic alpha-SMA protein levels and decreased in hydroxyproline and thiobarbituric acid reactive substances (TBARS) levels of BDL rats. On the other hand, the normalizing effect of YCHT (250mg/kg) on the TGF-beta1mRNA expression was independent on the dose of YCHT, 500mg/kg was not effectively changed the quantitative composition of mRNA levels. The study shows that hepatic hydroxyproline accumulation caused by hydrophilic bile acids accompanied by elevated hepatic lipid peroxidation, and hepatic collagen levels can be decreased in the presence of YCHT. In conclusion, long-term administration of YCHT in rats ameliorated the hydropholic bile acids induced hepatic injury that probably related to a reduced oxidant stress and degree of hepatic fibrosis.
肝脏中亲水性胆汁酸的积累被认为在肝损伤的诱导中起关键作用。茵陈蒿汤(YCHT)是由三种不同草药制成的水提取物:茵陈蒿(菊科)、栀子(茜草科)、大黄(蓼科),它已被公认为对各种肝病具有肝脏保护作用的药物。因此,我们使用胆道闭锁模型实验来测试茵陈蒿汤在肝纤维化发病机制中是否发挥调节作用。在实验性胆汁淤积动物模型中,通过胆总管结扎(BDL)27天造成伴有纤维化的肝损伤。手术后,每天一次口服给予茵陈蒿汤(250和500mg/kg体重),持续27天。BDL导致肝脏胶原蛋白显著沉积,这由α-SMA蛋白增加以及I型前胶原mRNA表达增加所证实。茵陈蒿汤显著降低了BDL大鼠肝脏α-SMA蛋白水平以及羟脯氨酸和硫代巴比妥酸反应性物质(TBARS)水平。另一方面,茵陈蒿汤(250mg/kg)对TGF-β1mRNA表达的归一化作用与茵陈蒿汤剂量无关,500mg/kg并未有效改变mRNA水平的定量组成。该研究表明,亲水性胆汁酸引起的肝脏羟脯氨酸积累伴随着肝脏脂质过氧化升高,而在茵陈蒿汤存在的情况下肝脏胶原蛋白水平可降低。总之,大鼠长期给予茵陈蒿汤可改善亲水性胆汁酸诱导的肝损伤,这可能与氧化应激降低和肝纤维化程度减轻有关。