Ginsenoside CK cooperates with bone mesenchymal stem cells to enhance angiogenesis post‐stroke via GLUT1 and HIF‐1α/VEGF pathway

• Published in: Phytotherapy research 2024-08, Vol.38 (8), p.4321-4335
• Main Authors: Chen, Xijun, Qian, Wenqi, Zhang, Ying, Zhao, Peiqi, Lin, Xiangxiang, Yang, Su, Zhuge, Qichuan, Ni, Haoqi
• Format: Article
• Language: English
• Subjects: Angiogenesis; Bone marrow; bone mesenchymal stem cell; brain; Cell differentiation; Cerebral blood flow; Differentiation; Energy metabolism; ginsenoside compound K; Ginsenosides; glucose; GLUT1; In vivo methods and tests; infarction; Ischemia; Mesenchymal stem cells; Microvasculature; neurons; Neuroprotection; neuroprotective effect; Occlusion; oxygen; phytotherapy; Signal transduction; Stem cell transplantation; Stem cells; Stroke; Survival; Synergistic effect; Vascular endothelial growth factor
• ISSN: 0951-418X; 1099-1573; 1099-1573
• DOI: 10.1002/ptr.8235

The transplantation of bone marrow mesenchymal stem cells (MSCs) in stroke is hindered by the restricted rates of survival and differentiation. Ginsenoside compound K (CK), is reported to have a neuroprotective effect and regulate energy metabolism. We applied CK to investigate if CK could promote the survival of MSCs and differentiation into brain microvascular endothelial‐like cells (BMECs), thereby alleviating stroke symptoms. Therefore, transwell and middle cerebral artery occlusion (MCAO) models were used to mimic oxygen and glucose deprivation (OGD) in vitro and in vivo, respectively. Our results demonstrated that CK had a good affinity for GLUT1, which increased the expression of GLUT1 and the production of ATP, facilitated the proliferation and migration of MSCs, and activated the HIF‐1α/VEGF signaling pathway to promote MSC differentiation. Moreover, CK cooperated with MSCs to protect BMECs, promote angiogenesis and vascular density, enhance neuronal and astrocytic proliferation, thereby reducing infarct volume and consequently improving neurobehavioral outcomes. These results suggest that the synergistic effects of CK and MSCs could potentially be a promising strategy for stroke. Ginsenoside CK promotes glucose uptake, ATP generation, tube formation, and migration by targeting GLUT1 protein on MSC through HIF‐1α/VEGF signaling pathway, thus promoting MSC differentiation into microvascular endothelial‐like cells.