A Biomedical Investigation of the Hepatoprotective Effect of Radix salviae miltiorrhizae and Network Pharmacology-Based Prediction of the Active Compounds and Molecular Targets.
A Biomedical Investigation of the Hepatoprotective Effect of Radix salviae miltiorrhizae and Network Pharmacology-Based Prediction of the Active Compounds and Molecular Targets.
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DOI：
10.3390/ijms18030620
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发表时间：
2017-03-13
影响因子：
5.6
通讯作者：
Feng Y
中科院分区：
文献类型：
--
作者：
Hong M;Li S;Wang N;Tan HY;Cheung F;Feng Y
丹参是一种经典的中药，几个世纪以来一直用于治疗肝脏疾病。本研究探讨丹参水提物对急性/慢性酒精性肝病（ALD）和非酒精性脂肪性肝病（NAFLD）的防治作用。体内实验结果表明，丹参可减轻ALD和NAFLD模型的肝脏炎症、脂肪变性和触觉纤维化。在作用机制方面，丹参在ALD和NAFLD模型中均显著降低MDA水平，提示丹参降低了氧化应激水平。然而，丹参处理不能激活ALD和NAFLD模型的内酶抗氧化系统。为了进一步探讨丹参的保肝机制，本研究采用基于硅基网络药理学的方法。药理网络分析结果显示，丹参酮iia、丹酚酸b、丹参素等6种潜在活性成分可能参与丹参素对ALD和NAFLD的保肝作用。其作用机制可能与调节细胞内分子靶点如PPARα、CYP1A2和MMP2，通过这些潜在的活性成分调节脂质代谢、抗氧化和抗纤维化有关。我们的研究表明，将网络药理学策略与体内实验研究相结合，可以为探索中药的作用机制和开发新的生物活性成分提供有力的工具。
Radix salviae miltiorrhizae (Danshen in Chinese), a classic traditional Chinese medicine (TCM) herb, has been used for centuries to treat liver diseases. In this study, the preventive and curative potential of Danshen aqueous extract on acute/chronic alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) was studied. The in vivo results indicated that Danshen could alleviate hepatic inflammation, fatty degeneration, and haptic fibrogenesis in ALD and NAFLD models. In the aspect of mechanism of action, the significant reduction in MDA levels in both ALD and NAFLD models implies the decreased levels of oxidative stress by Danshen. However, Danshen treatment could not activate the internal enzymatic antioxidant system in ALD and NAFLD models. To further explore the hepatoprotective mechanism of Danshen, an in silico-based network pharmacology approach was employed in the present study. The pharmacological network analysis result revealed that six potential active ingredients such as tanshinone iia, salvianolic acid b, and Danshensu may contribute to the hepatoprotective effects of Danshen on ALD and NAFLD. The action mechanism may relate with regulating the intracellular molecular targets such as PPARα, CYP1A2, and MMP2 for regulation of lipid metabolism, antioxidant and anti-fibrogenesis by these potential active ingredients. Our studies suggest that the combination of network pharmacology strategy with in vivo experimental study may provide a forceful tool for exploring the mechanism of action of traditional Chinese medicine (TCM) herb and developing novel bioactive ingredients.