Catalpol Alleviates Ischemic Stroke Through Promoting Angiogenesis and Facilitating Proliferation and Differentiation of Neural Stem Cells via the VEGF-A/KDR Pathway.

Abstract

Stroke is one of the leading causes of disability and death globally with a lack of effective therapeutic strategies. Catalpol is a bioactive compound derived from the traditional Chinese medicine Rehmannia glutinosa and it has been shown to be protective against various neurological diseases. The potential roles of catalpol against ischemic stroke are still not completely clear. In this study, we examined the effect and mechanism of catalpol against ischemic stroke using in vivo rat distal middle cerebral artery occlusion (dMCAO) and in vitro oxygen-glucose deprivation (OGD) models. We demonstrated that catalpol indeed attenuated the neurological deficits caused by dMCAO and improved neurological function. Catalpol remarkably promoted angiogenesis, promoted proliferation and differentiation of neural stem cells (NSCs) in the subventricular zone (SVZ), and prevented neuronal loss and astrocyte activation in the ischemic cortex or hippocampal dentate gyrus (DG) in vivo. The vascular endothelial growth factor receptor 2 (KDR, VEGFR-2) inhibitor SU5416 and VEGF-A shRNA were used to investigate the underlying mechanisms. The results showed that SU5416 administration or VEGF-A-shRNA transfection both attenuated the effects of catalpol. We also found that catalpol promoted the proliferation of cultured brain microvascular endothelial cells (BMECs) and the proliferation and differentiation of NSCs subjected to OGD insult in vitro. Interestingly, the impact of catalpol on cultured cells was also inhibited by SU5416. Moreover, catalpol was shown to protect NSCs against OGD indirectly by promoting BMEC proliferation in the co-cultured system. Taken together, catalpol showed therapeutic potential in cerebral ischemia by promoting angiogenesis and NSC proliferation and differentiation. The protective effects of catalpol were mediated through VEGF-A/KDR pathway activation.

• Authors: Si Sun, Yitong Xu, Ningxi Yu, Meifeng Zhang, Jinghui Wang, Dong Wan, Zhen Tian, Huifeng Zhu
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 60 Issue 11 Pg. 6227-6247 (Nov 2023) ISSN: 1559-1182 [Electronic] United States
• PMID: 37439957 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Vascular Endothelial Growth Factor A
• catalpol
• Vascular Endothelial Growth Factor Receptor-2
• Oxygen
• RNA, Small Interfering

Topics

• Rats
• Animals
• Ischemic Stroke (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (metabolism)
• Endothelial Cells (metabolism)
• Cell Differentiation
• Neural Stem Cells (metabolism)
• Oxygen (metabolism)
• Cell Proliferation
• RNA, Small Interfering (metabolism)
• Stroke (complications, drug therapy, metabolism)