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溪黄草提取物通过抑制TLR4-NF-κB信号通路对刀豆蛋白A诱导的小鼠急性肝损伤的保护作用。

Protective effect of Rabdosia amethystoides (Benth) Hara extract on acute liver injury induced by Concanavalin A in mice through inhibition of TLR4-NF-κB signaling pathway.

作者信息

Zhai Ke-Feng, Duan Hong, Cao Wen-Gen, Gao Gui-Zhen, Shan Ling-Ling, Fang Xue-Mei, Zhao Liang

机构信息

Institute of Pharmaceutical Biotechnology, School of Biological and Food Engineering, Engineering Research Center of Special Farm Seed Production, Suzhou University, 49, Bianhe Road, Suzhou, 234000, PR China.

Institute of Pharmaceutical Biotechnology, School of Biological and Food Engineering, Engineering Research Center of Special Farm Seed Production, Suzhou University, 49, Bianhe Road, Suzhou, 234000, PR China.

出版信息

J Pharmacol Sci. 2016 Feb;130(2):94-100. doi: 10.1016/j.jphs.2015.12.006. Epub 2016 Jan 4.

DOI:10.1016/j.jphs.2015.12.006
PMID:26823124
Abstract

Extract of Rabdosia amethystoides (Benth) Hara (ERA), a traditional Chinese medicine has antibacterial, antiviral, anti-tumor, anti-hepatitis and anti-inflammatory properties. However, the hepatoprotective effects and molecular mechanisms of ERA on acute liver injury have not been fully elucidated. This study aims to investigate the anti-inflammatory effect and liver protection of ERA against the acute liver injury induced by Concanavalin A (Con A) and its underlying molecular mechanisms in mice. Mice received ERA (50, 100, 150 mg/kg body weight) by gavage before Con A intravenous administration. We found that ERA pretreatment was able to significantly reduce the elevated serum alanine and aspartate aminotransferase levels and liver necrosis in Con A-induced hepatitis. In addition, ERA treatment significantly decreased the myeloperoxidase, malondialdehyde levels and augmented superoxide dismutase level in the liver tissue, and also suppressed the secretion of proinflammatory cytokines in the serum, compared with Con A group by enzyme linked immunosorbent assay. Furthermore, we observed that ERA pretreatment can significantly decrease the expression level of Toll-like receptor (TLR) 4 mRNA or protein in liver tissues. Further results showed that ERA pretreatment was capable of attenuating the activation of the NF-κB pathway by inhibiting IκBα kinase and p65 phosphorylation in Con A-induced liver injury. Our results demonstrate that ERA pretreatment has hepatoprotective property against Con A-induced liver injury through inhibition of inflammatory mediators in mice. The beneficial effect of ERA may be mediated by the downregulation of TLR4 expression and the inhibition of NF-κB activation.

摘要

冬凌草(Rabdosia amethystoides (Benth) Hara,ERA)是一种传统中药,具有抗菌、抗病毒、抗肿瘤、抗肝炎和抗炎特性。然而,ERA对急性肝损伤的肝保护作用及其分子机制尚未完全阐明。本研究旨在探讨ERA对刀豆蛋白A(Con A)诱导的小鼠急性肝损伤的抗炎和肝保护作用及其潜在分子机制。在静脉注射Con A之前,小鼠通过灌胃接受ERA(50、100、150 mg/kg体重)。我们发现,ERA预处理能够显著降低Con A诱导的肝炎中升高的血清丙氨酸和天冬氨酸转氨酶水平以及肝坏死。此外,与Con A组相比,ERA处理显著降低了肝组织中的髓过氧化物酶、丙二醛水平,并提高了超氧化物歧化酶水平,还通过酶联免疫吸附测定抑制了血清中促炎细胞因子的分泌。此外,我们观察到ERA预处理可显著降低肝组织中Toll样受体(TLR)4 mRNA或蛋白的表达水平。进一步结果表明,ERA预处理能够通过抑制Con A诱导的肝损伤中IκBα激酶和p65磷酸化来减弱NF-κB途径的激活。我们的结果表明,ERA预处理通过抑制小鼠炎症介质对Con A诱导的肝损伤具有肝保护作用。ERA的有益作用可能是通过下调TLR4表达和抑制NF-κB激活介导的。

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