Exploration in the Therapeutic and Multi-Target Mechanism of Ketamine on Cerebral Ischemia Based on Network Pharmacology and Molecular Docking.
Exploration in the Therapeutic and Multi-Target Mechanism of Ketamine on Cerebral Ischemia Based on Network Pharmacology and Molecular Docking.
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DOI：
10.2147/ijgm.s345884
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发表时间：
2022
影响因子：
2.3
通讯作者：
中科院分区：
文献类型：
--
作者：
氯胺酮以其分离性麻醉特性而闻名。它还具有镇痛、抗炎和抗衰老的作用，甚至具有脑保护作用。本研究旨在寻找氯胺酮作用靶点与临床疗效相关性的证据，并利用网络药理学的方法对氯胺酮抗脑缺血（CI）的多靶点机制进行研究。我们发现氯胺酮的临床意义可能比以前认为的更广泛。通过SwissTargetPrediction、DrugBank、PubChem、GeneCards和DisGeNET数据库预测氯胺酮的药物靶点和CI相关基因。用GO和KEGG分析氯胺酮的药物靶点与CI相关基因的交叉。我们预测了潜在靶点与氯胺酮之间的分子对接。结果表明，氯胺酮对CI的作用主要与α-突触核蛋白（SNCA）、毒蕈碱型乙酰胆碱受体M1（CHRM 1）和一氧化氮合酶1（NOS 1）有关。它主要调节昼夜节律传递、钙信号通路、多巴胺能突触、胆碱能突触和多巴胺能突触等信号通路。分子对接分析表明，氢键和π-π相互作用是主要的相互作用方式。氯胺酮在脑梗死治疗过程中影响的蛋白靶点。涉及298种蛋白质的三个关键靶点SNCA、CHRM 1和NOS 1已成为氯胺酮在CI治疗中的多靶点机制。同样，本研究也为将网络药理学引入脑梗死和脑保护多靶点药物的评价提供了新思路。
Ketamine is famous for its dissociative anesthetic properties. It is also analgesic, anti-inflammatory and anti-depressant, and even has a cerebral protective effect. We searched the evidence of the correlation between ketamine target and clinical efficacy and utilized network pharmacology to gather information about the multi-target mechanism of ketamine against cerebral ischemia (CI). We found that ketamine’s clinical significance may be more extensive than previously thought. The drug target of ketamine and CI-related genes were predicted by SwissTargetPrediction, DrugBank, PubChem, GeneCards and DisGeNET databases. The intersection of ketamine’s drug-targets and CI-related genes was analyzed by using GO and KEGG. We predicted the molecular docking between the potential target and ketamine. The results indicated that the effect of ketamine on CI was primarily associated with the target of α-synuclein (SNCA), muscarinic acetylcholine receptor M1 (CHRM1) and nitric oxide synthase 1 (NOS1). It principally regulates the signal pathways of circadian transmission, calcium signaling pathway, dopaminergic synapse, cholinergic synapse and glutamatergic synapse. Molecular docking analysis exhibited that hydrogen bond and Pi-Pi interaction were the predominant modes of interaction. There are protein targets affected by ketamine in the treatment of CI. Three pivotal targets involving 298 proteins, SNCA, CHRM1 and NOS1, have emerged as multi-target mechanisms for ketamine in CI therapy. Similarly, this study also provides a new idea for introducing network pharmacology into the evaluation of multi-targeted drugs for CI and cerebral protection.
影响因子：
4.7
作者：
Chen J;Zhang M;Zhou C;Ding Y;Fan N;He H
通讯作者：
He H