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

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

doi:10.3892/etm.2023.12108

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

Authors:
- Jiazhen Xu
- Yue Shen
- Pengwei Luan
- Haiying Wang
- Yulan Xu
- Lixian Jiang
- Ruixiang Li
- Feiyun Wang
- Yuying Zhu
- Jiange Zhang
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Affiliations: Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
Published online on: July 10, 2023 https://doi.org/10.3892/etm.2023.12108
Article Number: 409
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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