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Herbal formula Scutellariae radix and Rhei rhizoma attenuate dimethylnitrosamine-induced liver fibrosis in a rat model

机译:中药配方黄S和大黄对大鼠二甲基亚硝胺诱导的肝纤维化的缓解作用

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摘要

The bioactive components extracted from Scutellariae radix and Rhei rhizoma (SR) have been commonly used to treat liver diseases. The aim of this study was to verify the underlying mechanisms and antifibrotic effects of ethanol extract from the herbal combinatorial formula (SRE) in a dimethylnitrosamine (DMN)-administered rat model, with functional proteome tools. Our results indicated that the hepatic collagen content and alpha-smooth muscle actin expression were obviously alleviated by treatment with SRE. Comprehensive proteomics revealed global protein changes, and the network analysis implied that SRE application would attenuate oxidative stress and cytoskeleton dysregulation caused by DMN exposure. Next, marked downregulation of antioxidant enzymes mediated by DMN treatment was restored in the presence of SRE, while SRE treatment contributed to decreased MDA content. Moreover, protein carbonylation and DNA adduction induced by oxidative stress finally leading to liver injury were also reduced under SRE administration. These findings demonstrate that SRE could effectively prevent hepatic fibrosis mainly through regulating the redox status, and subsequently modulating the modification of intracellular molecules. Our experiments might help in developing novel therapeutic strategies against oxidation-caused liver diseases.
机译:从黄S和大黄根(SR)提取的生物活性成分通常用于治疗肝脏疾病。这项研究的目的是使用功能性蛋白质组学工具验证在二甲基亚硝胺(DMN)给药的大鼠模型中草药组合配方(SRE)乙醇提取物的潜在机制和抗纤维化作用。我们的结果表明,SRE处理可明显减轻肝胶原含量和α-平滑肌肌动蛋白的表达。全面的蛋白质组学揭示了全球蛋白质的变化,网络分析表明,SRE的应用将减轻DMN暴露引起的氧化应激和细胞骨架失调。接下来,在存在SRE的情况下恢复了DMN处理介导的抗氧化酶的显着下调,而SRE处理导致MDA含量降低。此外,在SRE给药后,氧化应激诱导的蛋白质羰基化和DNA加合最终导致肝损伤也减少了。这些发现表明,SRE主要可通过调节氧化还原状态并随后调节细胞内分子的修饰来有效预防肝纤维化。我们的实验可能有助于开发针对氧化性肝病的新型治疗策略。

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