Kadir Farkaad A, Kassim Normadiah M, Abdulla Mahmood Ameen, Kamalidehghan Behnam, Ahmadipour Fatemeh, Yehye Wageeh A
Department of Anatomy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
ScientificWorldJournal. 2014 Feb 20;2014:301879. doi: 10.1155/2014/301879. eCollection 2014.
The antifibrotic effects of traditional medicinal herb Caesalpinia sappan (CS) extract on liver fibrosis induced by thioacetamide (TAA) and the expression of transforming growth factor β1 (TGF-β1), α-smooth muscle actin (αSMA), and proliferating cell nuclear antigen (PCNA) in rats were studied. A computer-aided prediction of antioxidant and hepatoprotective activities was primarily performed with the Prediction Activity Spectra of the Substance (PASS) Program. Liver fibrosis was induced in male Sprague Dawley rats by TAA administration (0.03% w/v) in drinking water for a period of 12 weeks. Rats were divided into seven groups: control, TAA, Silymarin (SY), and CS 300 mg/kg body weight and 100 mg/kg groups. The effect of CS on liver fibrogenesis was determined by Masson's trichrome staining, immunohistochemical analysis, and western blotting. In vivo determination of hepatic antioxidant activities, cytochrome P450 2E1 (CYP2E1), and matrix metalloproteinases (MPPS) was employed. CS treatment had significantly increased hepatic antioxidant enzymes activity in the TAA-treated rats. Liver fibrosis was greatly alleviated in rats when treated with CS extract. CS treatment was noted to normalize the expression of TGF-β1, αSMA, PCNA, MMPs, and TIMP1 proteins. PASS-predicted plant activity could efficiently guide in selecting a promising pharmaceutical lead with high accuracy and required antioxidant and hepatoprotective properties.
研究了传统草药苏木（CS）提取物对硫代乙酰胺（TAA）诱导的大鼠肝纤维化的抗纤维化作用以及转化生长因子β1（TGF-β1）、α平滑肌肌动蛋白（αSMA）和增殖细胞核抗原（PCNA）的表达。首先使用物质预测活性谱（PASS）程序对抗氧化和肝保护活性进行计算机辅助预测。通过在饮用水中给予TAA（0.03% w/v）12周，诱导雄性Sprague Dawley大鼠肝纤维化。将大鼠分为七组：对照组、TAA组、水飞蓟素（SY）组以及CS 300 mg/kg体重组和100 mg/kg组。通过Masson三色染色、免疫组织化学分析和蛋白质印迹法确定CS对肝纤维化形成的影响。采用体内测定肝抗氧化活性、细胞色素P450 2E1（CYP2E1）和基质金属蛋白酶（MMPs）的方法。CS处理显著提高了TAA处理大鼠的肝抗氧化酶活性。用CS提取物处理的大鼠肝纤维化得到极大缓解。注意到CS处理使TGF-β1、αSMA、PCNA、MMPs和TIMP1蛋白的表达正常化。PASS预测的植物活性可以有效地指导高精度地选择具有所需抗氧化和肝保护特性的有前景的药物先导物。
