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三草颗粒对刀豆蛋白A诱导的小鼠肝损伤的保护作用及作用机制探究

Hepatoprotective Effect of San-Cao Granule on Con A-Induced Liver Injury in Mice and Mechanisms of Action Exploration.

作者信息

Yang YuXue, Zhang Ping, Wang Yingying, Wei Shizhang, Zhang Lu, Wang Jiabo, Lu Xiaohua, Zhou Houqin, Li Ruisheng, Wen Jianxia, Zhou Xuelin, Li Haotian, Li Kun, Zhao Yanling

机构信息

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Department of Pharmacy, 302 Military Hospital of China, Beijing, China.

出版信息

Front Pharmacol. 2018 Jun 12;9:624. doi: 10.3389/fphar.2018.00624. eCollection 2018.

Abstract

San-Cao granule (SCG), a traditional Chinese herb formula, has been used for treating autoimmune hepatitis (AIH) in our clinics for a long time. However, its active ingredients and mechanisms of action were still unknown due to its complicated chemical compositions. In the present study, the pharmacological study of SCG on acute liver injury induced by Concanavalin A (Con A) was performed to provide a scientific evidence for SCG against liver injury. In order to screen active components and predicate mechanisms of action, an "ingredients-target-disease" interaction network was constructed by network pharmacology. Then, the pharmacological study was performed to evaluate the therapeutic effect and the underlying mechanisms of SCG on Con A-induced liver injury in mice. This research demonstrated the pharmacological effect of SCG on Con A-induced liver injury, which was through improving the liver function, relieving the pathological changes of liver tissue, decreasing the level of pro-inflammatory cytokines, and thus balancing the pro- and anti-inflammatory cytokines. And the anti-inflammatory of SCG may advantage over the ursodeoxycholic acid (UDCA). Network pharmacology analysis revealed that the pharmacological effect of SCG might be related to its active ingredients of taraxanthin, dihydrotanshinone I, isotanshinone I, γ-sitosterol, 3β-acetyl-20,25-epoxydammarane-24α, and δ-7-stigmastenol. The hepatoprotective effect of SCG was reflected by suppressing Con A-induced apoptosis which was mediated by TRAIL and FASL. The combination of network pharmacology and experimental data has revealed the anti-apoptotic effect of SCG against Con A-induced liver injury.

摘要

三草颗粒(SCG)是一种传统中药配方,长期以来一直在我们的诊所用于治疗自身免疫性肝炎(AIH)。然而,由于其化学成分复杂,其活性成分和作用机制仍不清楚。在本研究中,进行了SCG对刀豆蛋白A(Con A)诱导的急性肝损伤的药理研究,为SCG抗肝损伤提供科学依据。为了筛选活性成分并推断作用机制,通过网络药理学构建了一个“成分-靶点-疾病”相互作用网络。然后,进行药理研究以评估SCG对Con A诱导的小鼠肝损伤的治疗效果和潜在机制。本研究证明了SCG对Con A诱导的肝损伤的药理作用,即通过改善肝功能、减轻肝组织病理变化、降低促炎细胞因子水平,从而平衡促炎和抗炎细胞因子。并且SCG的抗炎作用可能优于熊去氧胆酸(UDCA)。网络药理学分析表明,SCG的药理作用可能与其活性成分蒲公英黄素、二氢丹参酮I、异丹参酮I、γ-谷甾醇、3β-乙酰基-20,25-环氧达玛烷-24α和δ-7-豆甾烯醇有关。SCG的肝保护作用通过抑制由TRAIL和FASL介导的Con A诱导的细胞凋亡来体现。网络药理学与实验数据的结合揭示了SCG对Con A诱导的肝损伤的抗凋亡作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffe/6005824/397727eaaf72/fphar-09-00624-g001.jpg

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