Baicalin Attenuates Alcoholic Liver Injury through Modulation of Hepatic Oxidative Stress, Inflammation and Sonic Hedgehog Pathway in Rats
Baicalin Attenuates Alcoholic Liver Injury through Modulation of Hepatic Oxidative Stress, Inflammation and Sonic Hedgehog Pathway in Rats
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DOI：
10.1159/000447820
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发表时间：
2016-01-01
影响因子：
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通讯作者：
Du, Shiyu
中科院分区：
文献类型：
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作者：
Wang, Huifen;Zhang, Yanli;Du, Shiyu
背景/目标：脂质积累、炎症反应和氧化应激与酒精性肝病（ALD）的病理学有关。靶向抑制这些特征可能为ALD提供有希望的治疗策略。黄芩苷是一种从黄芩中分离的黄酮类化合物，已被证明具有保肝作用。然而，其对ALD的影响仍然不清楚。本研究旨在探讨黄芩苷对酒精性肝损伤的保护作用及其机制。研究方法：在体内实验中，大鼠连续灌胃给予酒精4或8周，然后在后4周在有/无酒精摄入的情况下接受黄芩苷治疗。对肝脏组织学和功能、炎性细胞因子、氧化介质和Sonic hedgehog通路的组分进行了评价。对于体外实验，使用酒精刺激的人正常肝细胞LO 2。结果如下：黄芩苷能明显减轻酒精性肝损伤，改善酒精性肝功能损害，抑制肝细胞凋亡。黄芩苷还能降低促炎细胞因子TNF-α、IL-1 β、IL-6和丙二醛（MDA）的表达，提高抗氧化酶SOD和GSH-Px的活性。黄芩苷还能调节Shh信号通路的激活。黄芩苷的给药上调了音刺猬（Shh），补丁（Ptc），平滑（Smo）和胶质母细胞瘤-1（Gli-1）的表达。在体外阻断环巴胺的Shh通路可消除黄芩苷的作用。总结：体内和体外实验结果均表明黄芩苷通过抑制氧化应激、炎症反应和调节Shh通路在酒精诱导的肝损伤中发挥保肝作用。(C)2016作者（s）由S. Karger AG，巴塞尔
Background/Aims: Lipid accumulation, inflammatory responses and oxidative stress have been implicated in the pathology of alcoholic liver disease (ALD). Targeting inhibition of these features may provide a promising therapeutic strategy for ALD. Baicalin, a flavonoid isolated from Scutellaria boicatensis Georgi, has been shown to exert a hepatoprotective effect. However, its effects on ALD remain obscure. This study was aimed to investigate the effects of baicalin on alcohol-induced liver injury and its related mechanisms. Methods: For in vivo experiments, rats were supplied intragastrical administration of alcohol continuously for 4 or 8 weeks, and then received baicalin treatment in the latter 4 weeks in the presence / absence of alcohol intake. Liver histology and function, inflammatory cytokines, oxidative mediators, and the components of the Sonic hedgehog pathway were evaluated. For in vitro experiments, alcohol-stimulated human normal liver cells LO2 were used. Results: Baicalin treatment significantly alleviated alcoholic liver injury, improved liver function impaired by alcohol, and inhibited hepatocytes apoptosis. In addition, baicalin decreased the expression levels of proinflammatory cytokines (TNF-alpha, IL-1 beta, IL-6) and malonyldialdehyde (MDA), and increased the activities of antioxidant enzymes SOD and GSH-Px. Furthermore, baicalin modulated the activation of Sonic hedgehog (Shh) pathway. Administration of baicalin upregulated the expression of sonic hedgehog (Shh), patched (Ptc), Smoothened (Smo), and Glioblastoma-1(Gli-1). Blockade of the Shh pathway in cyclopamine abolished the effects of baicalin in vitro. Conclusion: Both in vivo and in vitro experimental results indicate that baicalin exerts hepatoprotective roles in alcohol-induced liver injury through inhibiting oxidative stress, inflammatory response, and the regulation of the Shh pathway. (C) 2016 The Author(s) Published by S. Karger AG, Basel