2. Academic Validation
  3. Ginsenoside F1 promotes angiogenesis by activating the IGF-1/IGF1R pathway

Ginsenoside F1 promotes angiogenesis by activating the IGF-1/IGF1R pathway

  • Pharmacol Res. 2019 Jun;144:292-305. doi: 10.1016/j.phrs.2019.04.021.
Jiayan Zhang 1,  Mingqun Liu 1,  Maohua Huang 1,  Minfeng Chen 1,  Dong Zhang 2,  Liangping Luo 2,  Geni Ye 1,  Lijuan Deng 3,  Yinghui Peng 1,  Xin Wu 4,  Guanping Liu 4,  Wencai Ye 5,  Dongmei Zhang 6
Affiliations

Affiliations

  • 1 College of Pharmacy, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou 510632, China.
  • 2 Department of Medical Imaging Centre, The First Affiliated Hospital, Jinan University, Guangzhou, China.
  • 3 Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
  • 4 Guangxi Engineering Research Center of Innovative Preparations for Natural Medicine, Guangxi Wuzhou Pharmaceutical (Group) Co., Ltd, Wuzhou 543000, China.
  • 5 College of Pharmacy, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou 510632, China. Electronic address: chywc@aliyun.com.
  • 6 College of Pharmacy, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou 510632, China. Electronic address: dmzhang701@jnu.edu.cn.
PMID: 31048033 DOI: 10.1016/j.phrs.2019.04.021
Abstract

Ischemic stroke is one of the most lethal and highly disabling diseases that seriously affects the human health and quality of life. A therapeutic angiogenic strategy has been proposed to alleviate ischemia-induced injury by promoting angiogenesis and improving cerebrovascular function in the ischemic regions. The insulin-like growth factor 1 (IGF-1)/insulin-like growth factor 1 receptor (IGF1R) axis is crucial for cerebral angiogenesis and neurogenesis. However, effective drugs that prevent cerebral ischemic injury by inducing cerebral angiogenesis via activation of the IGF1R pathway are lacking. Here, we screened a pro-angiogenic agent ginsenoside F1 (GF1), a ginseng saponin isolated from a traditional Chinese medicine that was widely used in ischemic stroke treatment. It promoted the proliferation, mobility and tube formation of human umbilical vein endothelial cells and human brain microvascular endothelial cells, as well as pericytes recruitment to the endothelial tubes. GF1 stimulated vessel sprouting in the rat arterial ring and facilitated neovascularization in chicken embryo chorioallantoic membrane (CAM). In the in vivo experiments, GF1 rescued the axitinib-induced vascular defect in zebrafish. It also increased the microvessel density (MVD) and improved focal cerebral blood perfusion in the rat middle cerebral artery occlusion (MCAO) model. Mechanism studies revealed that GF1-induced angiogenesis depended on IGF1R activation mediated by the autocrine IGF-1 loop in endothelial cells. Based on our findings, GF1-induced activation of the IGF-1/IGF1R pathway to promote angiogenesis is an effective approach to alleviate cerebral ischemia, and GF1 is a potential agent that improves cerebrovascular function and promotes recovery from ischemic stroke.

Keywords

Angiogenesis; Axitinib (PubChem CID: 131871370); Cerebral ischemia; Ginsenoside F1; Ginsenoside F1 (PubChem CID: 53447401); Insulin-like growth factor 1; Insulin-like growth factor 1 receptor; OSI-906 (PubChem CID:11640390).

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