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Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS,a Natural Vasoprotective Combination,for the Phytotherapy of Coronary Artery Disease
Authors:You-Gang Zhang  Xia-Xia Liu  Jian-Cheng Zong  Yang-Teng-Jiao Zhang  Rong Dong  Na Wang  Zhi-Hui Ma  Li Li  Shang-Long Wang  Yan-Ling Mu  Song-Song Wang  Zi-Min Liu  Li-Wen Han
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.
Keywords:coronary artery disease   phytotherapy   network pharmacology   angiogenesis   zebrafish   dynamics molecular docking
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