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黄芩苷和栀子苷改善脑缺血损伤机制的网络药理学研究。

Network pharmacology identification of mechanisms of cerebral ischemia injury amelioration by Baicalin and Geniposide.

机构信息

Shaanxi University of Chinese Medicine, Xianyang, 712046, China.

Shaanxi University of Chinese Medicine, Xianyang, 712046, China.

出版信息

Eur J Pharmacol. 2019 Sep 15;859:172484. doi: 10.1016/j.ejphar.2019.172484. Epub 2019 Jun 20.

Abstract

Cerebral ischemia is one of the main causes of human neurological dysfunction. Baicalin (BC) and Geniposide (GP) and their combination (BC/GP) have an ameliorative effect on cerebral ischemia. Here, we use network pharmacology to predict the targets of BC, GP and BC/GP, then explored the protective mechanisms of the drugs on cerebral ischemia injury caused by abnormal activation of microglia cells in vitro. The results indicate that 45 targets related to cerebral ischemic injury were predicted by network pharmacology, and 26 cerebral ischemia related pathways were extracted by the KEGG database. In vitro lipopolysaccharide (LPS) stimulated BV-2 cells to establish a model of inflammatory injury induced by microglia. The effects of BC, GP and BC/GP on the expression of TNF-α, IL-1β and IL-10, TGF-β and TNF-α were verified. Network pharmacology predicts the regulation of the 5-LOX/CysLTs inflammatory pathway. Finally, we found that GP and BC/GP exert anti-inflammatory and neuroprotective effects by regulating the polarization state of microglia and down-regulating 5-LOX/CysLTs, and has certain protective effects on nerve damage following cerebral ischemia.

摘要

脑缺血是人类神经功能障碍的主要原因之一。黄芩苷(BC)、栀子苷(GP)及其联合用药(BC/GP)对脑缺血具有改善作用。在这里,我们使用网络药理学来预测 BC、GP 和 BC/GP 的靶点,然后探讨这些药物在体外异常激活小胶质细胞引起的脑缺血损伤中的保护机制。结果表明,网络药理学预测了 45 个与脑缺血损伤相关的靶点,并从 KEGG 数据库中提取了 26 个与脑缺血相关的途径。体外脂多糖(LPS)刺激 BV-2 细胞建立小胶质细胞炎症损伤模型,验证 BC、GP 和 BC/GP 对 TNF-α、IL-1β 和 IL-10、TGF-β 和 TNF-α 表达的影响。网络药理学预测了 5-LOX/CysLTs 炎症通路的调节。最后,我们发现 GP 和 BC/GP 通过调节小胶质细胞的极化状态和下调 5-LOX/CysLTs 发挥抗炎和神经保护作用,对脑缺血后的神经损伤具有一定的保护作用。

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