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基于网络药理学的研究探讨天然血管保护组合 DGS 治疗冠心病的潜在成分和作用机制。

Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS, a Natural Vasoprotective Combination, for the Phytotherapy of Coronary Artery Disease.

机构信息

School of Pharmacy and Pharmaceutical Science, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250000, China.

School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030000, China.

出版信息

Molecules. 2022 Jun 24;27(13):4075. doi: 10.3390/molecules27134075.

DOI:10.3390/molecules27134075
PMID:35807320
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9268537/
Abstract

Phytotherapy offers obvious advantages in the intervention of Coronary Artery Disease (CAD), but it is difficult to clarify the working mechanisms of the medicinal materials it uses. DGS is a natural vasoprotective combination that was screened out in our previous research, yet its potential components and mechanisms are unknown. Therefore, in this study, HPLC-MS and network pharmacology were employed to identify the active components and key signaling pathways of DGS. Transgenic zebrafish and HUVECs cell assays were used to evaluate the effectiveness of DGS. A total of 37 potentially active compounds were identified that interacted with 112 potential targets of CAD. Furthermore, PI3K-Akt, MAPK, relaxin, VEGF, and other signal pathways were determined to be the most promising DGS-mediated pathways. NO kit, ELISA, and Western blot results showed that DGS significantly promoted NO and VEGFA secretion via the upregulation of VEGFR2 expression and the phosphorylation of Akt, Erk1/2, and eNOS to cause angiogenesis and vasodilation. The result of dynamics molecular docking indicated that Salvianolic acid C may be a key active component of DGS in the treatment of CAD. In conclusion, this study has shed light on the network molecular mechanism of DGS for the intervention of CAD using a network pharmacology-driven strategy for the first time to aid in the intervention of CAD.

摘要

植物疗法在干预冠状动脉疾病(CAD)方面具有明显优势,但难以阐明其所用药材的作用机制。DGS 是我们之前的研究中筛选出的一种天然血管保护组合,但它的潜在成分和机制尚不清楚。因此,在这项研究中,我们采用 HPLC-MS 和网络药理学方法来鉴定 DGS 的活性成分和关键信号通路。利用转基因斑马鱼和 HUVECs 细胞实验来评估 DGS 的功效。共鉴定出 37 种潜在的活性化合物,这些化合物与 CAD 的 112 个潜在靶点相互作用。此外,确定 PI3K-Akt、MAPK、松弛素、VEGF 等信号通路是 DGS 介导的最有前途的途径。NO 试剂盒、ELISA 和 Western blot 结果表明,DGS 通过上调 VEGFR2 表达和磷酸化 Akt、Erk1/2 和 eNOS,显著促进了 NO 和 VEGFA 的分泌,从而引起血管生成和血管舒张。动态分子对接结果表明,丹酚酸 C 可能是 DGS 治疗 CAD 的关键活性成分。总之,本研究首次采用网络药理学驱动的策略,阐明了 DGS 干预 CAD 的网络分子机制,为 CAD 的干预提供了一定的参考依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/88a1b4f1a2d8/molecules-27-04075-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/cf4caceff3ff/molecules-27-04075-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/687b4edb19b7/molecules-27-04075-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/5c58bc20d64c/molecules-27-04075-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/3b28a2b4638f/molecules-27-04075-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/f80e925f57fc/molecules-27-04075-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/88a1b4f1a2d8/molecules-27-04075-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/cf4caceff3ff/molecules-27-04075-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/86e9e1bca0fb/molecules-27-04075-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/687b4edb19b7/molecules-27-04075-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/43345ba596ec/molecules-27-04075-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/5c58bc20d64c/molecules-27-04075-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/3b28a2b4638f/molecules-27-04075-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/f80e925f57fc/molecules-27-04075-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a6/9268537/88a1b4f1a2d8/molecules-27-04075-g008.jpg

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