Saravanan Nadana, Nalini Namasivayam
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar - 608 002, Tamilnadu, India.
Fundam Clin Pharmacol. 2007 Oct;21(5):507-14. doi: 10.1111/j.1472-8206.2007.00500.x.
The study evaluates the inhibitory activity of ethanolic root extract of Hemidesmus indicus (H. indicus) and its active principle 2-hydroxy 4-methoxy benzoic acid (HMBA) on liver fibrotic markers and characteristics such as collagen content, matrix metalloproteinases (MMPs) 2 and 9 in ethanol-fed rats. Experimental groups were control, H. indicus (500 mg/kg body weight every day during the last 30 days), HMBA (200 microg/kg body weight every day during the last 30 days), alcohol (5 g/kg body weight by intragastric intubation everyday, i.e. throughout the experimental period of 60 days), alcohol plus H. indicus and alcohol plus HMBA. Ethanol administration significantly increased the levels of liver collagen and hydroxy proline content, cross-linked fluorescence, shrinkage temperature and lipid peroxidation and significantly decreased the solubility of liver collagen and the ascorbic acid content when compared with control rats. On treatment with H. indicus and HMBA the ethanol-fed rats showed significantly reduced levels of liver collagen and hydroxyproline content, cross-linked fluorescence, shrinkage temperature and lipid peroxidation and enhanced solubility of liver collagen and ascorbic acid levels when compared with untreated ethanol-fed rats. MMPs were extracted from the liver of control, H. indicus-treated, HMBA-treated, ethanol-administered, ethanol with H. indicus-coadministered and ethanol with HMBA-coadministered rats. The inhibition was analyzed by gelatin zymography and the percentage of expression was determined by a gel documentation system. The activities of MMPs 2 and 9 were significantly increased in ethanol-supplemented rats. Cotreatment of H. indicus/HMBA with ethanol showed significantly decreased activities of these enzymes when compared with those of the untreated rats. H. indicus/HMBA alone treatment showed no such significant alterations. Thus, our present study reveals the strong inhibitory activity of H. indicus and HMBA on the quantitative and qualitative properties of hepatic collagen and also MMPs involved in the extracellular matrix degradation during ethanol intoxication.
本研究评估了印度牛弥菜（H. indicus）乙醇根提取物及其活性成分2-羟基-4-甲氧基苯甲酸（HMBA）对乙醇喂养大鼠肝脏纤维化标志物及特征（如胶原蛋白含量、基质金属蛋白酶（MMPs）2和9）的抑制活性。实验组包括对照组、印度牛弥菜组（在最后30天每天500毫克/千克体重）、HMBA组（在最后30天每天200微克/千克体重）、酒精组（每天通过胃内插管给予5克/千克体重，即整个60天实验期）、酒精加印度牛弥菜组以及酒精加HMBA组。与对照大鼠相比，给予乙醇显著增加了肝脏胶原蛋白和羟脯氨酸含量、交联荧光、收缩温度以及脂质过氧化水平，并显著降低了肝脏胶原蛋白的溶解度和抗坏血酸含量。与未治疗的乙醇喂养大鼠相比，用印度牛弥菜和HMBA治疗的乙醇喂养大鼠肝脏胶原蛋白和羟脯氨酸含量、交联荧光、收缩温度以及脂质过氧化水平显著降低，肝脏胶原蛋白溶解度和抗坏血酸水平提高。从对照组、印度牛弥菜治疗组、HMBA治疗组、乙醇给药组、乙醇与印度牛弥菜共同给药组以及乙醇与HMBA共同给药组大鼠的肝脏中提取MMPs。通过明胶酶谱分析抑制情况，并通过凝胶成像系统测定表达百分比。在补充乙醇的大鼠中，MMPs 2和9的活性显著增加。与未治疗大鼠相比，印度牛弥菜/HMBA与乙醇共同处理显示这些酶的活性显著降低。单独给予印度牛弥菜/HMBA未显示出此类显著变化。因此，我们目前的研究揭示了印度牛弥菜和HMBA对肝脏胶原蛋白的定量和定性特性以及乙醇中毒期间参与细胞外基质降解的MMPs具有强大的抑制活性。
