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基于电压门控钠离子通道蛋白预测和验证延胡索中潜在的镇痛和抗心律失常先导成分。

Prediction and verification of potential lead analgesic and antiarrhythmic components in Corydalis yanhusuo W. T. Wang based on voltage-gated sodium channel proteins.

机构信息

School of Life Sciences and Biopharmaceutical Science, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.

School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.

出版信息

Int J Biol Macromol. 2022 Sep 1;216:537-546. doi: 10.1016/j.ijbiomac.2022.07.024. Epub 2022 Jul 7.

Abstract

Corydalis yanhusuo W. T. Wang, a traditional Chinese herbal medicine, has been used as an analgesic for thousands of years and it also promotes blood circulation. In this study, 33 Corydalis yanhusuo alkaloid active components were acquired from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). A total of 543 pain-related targets, 1774 arrhythmia targets, and 642 potential targets of these active components were obtained using Swiss Target Prediction, GeneCards, Open Target Platform, and Therapeutic Target Database. Fifty intersecting targets were visualized through a Venn diagram, KEGG and GO pathway enrichment analysis. The analysis proposed that sodium ion channels are likely potential targets of Corydalis yanhusuo active components as analgesia and anti-arrhythmia agents. Molecular docking showed that the 33 components could bind to Nav1.7 and Nav1.5 (two subtypes of ion channel proteins) with different binding energies. In a patch clamp study, dihydrosanguinarine and dihydrochelerythrine, two monomers with the strongest binding effects, could inhibit the peak currents and promote both activation and inactivation phases of Nav1.5. Meanwhile, dihydrosanguinarine and dihydrochelerythrine could also inhibit peak currents and promote the activation phase of Nav1.7. Therefore, the findings from this study provide valuable information for future uses of traditional Chinese medicines to treat pain and cardiovascular disease.

摘要

延胡索是一种传统的中药,已有数千年的历史,被用作镇痛药,同时具有促进血液循环的作用。在这项研究中,从中药数据库和分析平台(TCMSP)中获取了 33 种延胡索生物碱活性成分。通过瑞士靶点预测、基因卡片、开放靶点平台和治疗靶点数据库,共获得了 543 个与疼痛相关的靶点、1774 个心律失常靶点和 642 个这些活性成分的潜在靶点。通过 Venn 图、KEGG 和 GO 通路富集分析可视化了 50 个交集靶点。分析提出,钠离子通道可能是延胡索活性成分作为镇痛药和抗心律失常药物的潜在靶点。分子对接表明,这 33 种成分可以与 Nav1.7 和 Nav1.5(两种离子通道蛋白亚型)以不同的结合能结合。在膜片钳研究中,二氢血根碱和二氢白屈菜红碱这两种结合作用最强的单体,可以抑制 Nav1.5 的峰电流,并促进其激活和失活阶段。同时,二氢血根碱和二氢白屈菜红碱也可以抑制 Nav1.7 的峰电流并促进其激活阶段。因此,这项研究的结果为未来利用中药治疗疼痛和心血管疾病提供了有价值的信息。

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