Pro‑angiogenic activity of salvianolate and its potential therapeutic effect against acute cerebral ischemia

Jiazhen Xu; Yue Shen; Pengwei Luan; Haiying Wang; Yulan Xu; Lixian Jiang; Ruixiang Li; Feiyun Wang; Yuying Zhu; Jiange Zhang

doi:10.3892/etm.2023.12108

Pro‑angiogenic activity of salvianolate and its potential therapeutic effect against acute cerebral ischemia

Exp Ther Med. 2023 Jul 10;26(2):409. doi: 10.3892/etm.2023.12108. eCollection 2023 Aug.

Authors

Jiazhen Xu^{1

2}, Yue Shen³, Pengwei Luan¹, Haiying Wang³, Yulan Xu¹, Lixian Jiang¹, Ruixiang Li¹, Feiyun Wang¹, Yuying Zhu¹, Jiange Zhang^{1

4}

Affiliations

¹ Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
² Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong 266071, P.R. China.
³ School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
⁴ Shanghai Frontiers Science Center for Traditional Chinese Medicine Chemical Biology, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.

Abstract

Salvianolate (Sal) is a medicinal composition that is widely used in China for the treatment of coronary heart disease and angina pectoris. The aim of the present study was to investigate the potential macrophage-mediated pro-angiogenic effects of Sal in vitro. In addition, another aim was to explore the effects of Sal in a rat model of transient middle cerebral artery occlusion (tMCAO) along with the potential mechanism by which it promotes angiogenesis. In this study, human umbilical vein endothelial cells (HUVECs) and Raw264.7 macrophages in vitro, and a rat tMCAO model in vivo were used to detect the pro-angiogenic effect and mechanism of Sal. The results of in vitro experiments showed that the viability, migration and tube formation of HUVECs were promoted by the supernatant of Sal-treated Raw264.7 macrophages (s-Sal) but not by Sal alone. s-Sal also increased the levels of phosphorylated (p-)VEGFR-2, p-AKT and p-p38 MAPK in HUVECs while Sal alone did not. In vivo, treatment with Sal significantly reduced the cerebral infarction volume and neurological deficit scores in the rat tMCAO model. Similar to the mechanism observed in the in vitro experiments, Sal treatment upregulated the protein expression of VEGF and VEGFR-2, in addition to the phosphorylation of VEGFR-2, AKT and p38, in the brain tissues of the tMCAO model rats. In summary, the results of the present study suggest that the mechanism of Sal-mediated angiogenesis is associated with stimulation of the VEGF/VEGFR-2 signaling pathway by macrophages. This suggests the potential of Sal as a therapeutic option for the treatment of acute cerebral ischemic injury, which may act via the promotion of angiogenesis.

Keywords: angiogenesis; ischemic stroke; macro; salvianolate.

Grants and funding

Funding: This study was supported by grants from the National Natural Science Foundation of China (grant no. 82003800), the Shanghai Municipal Education Commission (grant no. 2019-01-07-00-10-E00072), Shanghai Municipal Health Commission/Shanghai Municipal Administration of Traditional Chinese Medicine [grant no. ZY(2021-2023)-0501], Shanghai Science and Technology Development Fund from Central Leading Local Government (grant no. YDZX20223100001004), Science and Technology Commission of Shanghai Municipality (grant no. 20ZR1473200), ‘Chenguang Program’ supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission (grant no. 21CGA51), Open Project of National Major Scientific and Technological Infrastructure for Translational Medicine (Shanghai) (grant no. TMSK-2021-405) and Open Project of Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs (grant no. SMECD2022004).