Department of Emergency, China-Japan Friendship Hospital, Beijing, 100029, China.
Department of Neurology, Beijing University of Chinese Medicine Dongfang Hospital, Beijing, 100078, China.
Chin J Integr Med. 2024 Aug;30(8):713-720. doi: 10.1007/s11655-024-3910-6. Epub 2024 Jun 24.
To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation.
The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions.
We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ.
The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.
基于网络药理学和体内实验验证，探讨痰热清注射液（TRQ）治疗缺血性脑卒中的神经保护作用及机制。
根据已发表数据检索 TRQ 的化学成分，从 PubChem、治疗靶点数据库和 DrugBank 中检索靶点。使用 Cytoscape 进行网络可视化和分析，从 STRING 数据库中获取蛋白质-蛋白质相互作用网络。使用京都基因与基因组百科全书（KEGG）通路和基因本体论（GO）分析进行富集分析。在体内实验中，采用大脑中动脉闭塞（MCAO）模型。通过 2,3,5-三苯基氯化四氮唑（TTC）染色测定梗死体积，通过 Western blot 分析蛋白表达。进行分子对接以预测配体-受体相互作用。
我们筛选了 TRQ 中的 81 种化学化合物，并检索了它们的治疗靶点。在这些靶点中，有 116 个是治疗脑卒中的靶点。富集分析表明，apelin 信号通路是缺血性脑卒中的关键通路。此外，在体内实验中，我们发现腹腔注射 2.5 mL/kg TRQ 每 6 h 可显著减少 MCAO 大鼠的梗死体积（P<0.05）。此外，TRQ 可增加 apelin 受体（APJ）/磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）通路的蛋白水平（P<0.05）。此外，TRQ 中的 41 种化学化合物可与 APJ 结合。
TRQ 的神经保护作用可能与 APJ/PI3K/AKT 信号通路有关。但是，需要进一步的研究来证实这一发现。
