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

**You-Gang Zhang 1,†, Xia-Xia Liu 1,2,†, Jian-Cheng Zong 3,† , Yang-Teng-Jiao Zhang <sup>1</sup> , Rong Dong <sup>1</sup> , Na Wang 1,2 , Zhi-Hui Ma 1,4, Li Li <sup>3</sup> , Shang-Long Wang <sup>3</sup> , Yan-Ling Mu <sup>1</sup> , Song-Song Wang <sup>1</sup> , Zi-Min Liu 5,\* and Li-Wen Han 1,\***


**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
