Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Zhejiang-US Joint Laboratory for Aging and Neurological Disease Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Phytother Res. 2024 Aug;38(8):4321-4335. doi: 10.1002/ptr.8235. Epub 2024 Jul 11.
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.
骨髓间充质干细胞（MSCs）移植治疗脑卒中受到其存活和分化能力有限的限制。研究表明，人参皂苷化合物 K（CK）具有神经保护作用，并能调节能量代谢。本研究应用 CK 来探讨 CK 是否能促进 MSCs 的存活和向脑微血管内皮样细胞（BMECs）的分化，从而缓解脑卒中症状。因此，我们采用 Transwell 实验和大脑中动脉闭塞（MCAO）模型分别模拟体外和体内的氧糖剥夺（OGD）。结果表明，CK 与人 GLUT1 有很好的亲和力，增加了 GLUT1 的表达和 ATP 的产生，促进了 MSCs 的增殖和迁移，并激活了 HIF-1α/VEGF 信号通路，促进 MSC 的分化。此外，CK 与 MSCs 协同作用保护 BMECs，促进血管生成和血管密度增加，增强神经元和星形胶质细胞的增殖，从而减少梗死体积，改善神经行为学结局。这些结果表明，CK 和 MSCs 的协同作用可能是治疗脑卒中的一种有前途的策略。
