Catalpol attenuates ischemic stroke by promoting neurogenesis and angiogenesis via the SDF-1α/CXCR4 pathway
作者全名：Zhang, Mei-feng; Wang, Jing-hui; Sun, Si; Xu, Yi-tong; Wan, Dong; Feng, Shan; Tian, Zhen; Zhu, Hui-feng
作者地址：[Zhang, Mei-feng; Wang, Jing-hui; Sun, Si; Xu, Yi-tong; Feng, Shan; Tian, Zhen; Zhu, Hui-feng] Southwest Univ, Coll Pharmaceut Sci, 2 Tiansheng Rd, Chongqing 400715, Peoples R China; [Wan, Dong] Chongqing Med Univ, Affiliated Hosp 1, Dept Emergency & Crit Care Med, Chongqing 400016, Peoples R China
通信作者：Tian, Z; Zhu, HF (通讯作者)，Southwest Univ, Coll Pharmaceut Sci, 2 Tiansheng Rd, Chongqing 400715, Peoples R China.
来源：PHYTOMEDICINE
ESI学科分类：PHARMACOLOGY & TOXICOLOGY
WOS号：WOS:001222079300001
JCR分区：Q1
影响因子：6.7
年份：2024
卷号：128
期号：
开始页：
结束页：
文献类型：Article
关键词：Catalpol; Brain ischemia; Neural stem cell; Migration; Brain microvascular endothelial cells
摘要：Background: Stroke is a leading cause of disability and death worldwide. Currently, there is a lack of clinically effective treatments for the brain damage following ischemic stroke. Catalpol is a bioactive compound derived from the traditional Chinese medicine Rehmannia glutinosa and shown to be protective in various neurological diseases. However, the potential roles of catalpol against ischemic stroke are still not completely clear. Purpose: This study aimed to further elucidate the protective effects of catalpol against ischemic stroke. Methods: A rat permanent middle cerebral artery occlusion (pMCAO) and oxygen-glucose deprivation (OGD) model was established to assess the effect of catalpol in vivo and in vitro, respectively. Behavioral tests were used to examine the effects of catalpol on neurological function of ischemic rats. Immunostaining was performed to evaluate the proliferation, migration and differentiation of neural stem cells (NSCs) as well as the angiogenesis in each group. The protein level of related molecules was detected by western-blot. The effects of catalpol on cultured NSCs as well as brain microvascular endothelial cells (BMECs) subjected to OGD in vitro were also examined by similar methods. Results: Catalpol attenuated the neurological deficits and improved neurological function of ischemic rats. It stimulated the proliferation of NSCs in the subventricular zone (SVZ), promoted their migration to the ischemic cortex and differentiation into neurons or glial cells. At the same time, catalpol increased the cerebral vessels density and the number of proliferating cerebrovascular endothelial cells in the infracted cortex of ischemic rats. The level of SDF-1 alpha and CXCR4 in the ischemic cortex was found to be enhanced by catalpol treatment. Catalpol was also shown to promote the proliferation and migration of cultured NSCs as well as the proliferation of BMECs subjected to OGD insult in vitro . Interestingly, the impact of catalpol on cultured cells was inhibited by CXCR4 inhibitor AMD3100. Moreover, the culture medium of BMECs containing catalpol promoted the proliferation of NSCs, which was also suppressed by AMD3100. Conclusion: Our data demonstrate that catalpol exerts neuroprotective effects by promoting neurogenesis and angiogenesis via the SDF-1 alpha/CXCR4 pathway, suggesting the therapeutic potential of catalpol in treating cerebral ischemia.
基金机构：National Natural Science Foundation of China [81873034, 81801329]; Chongqing Natural Science Foundation [CSTB2022NSCQ-MSX1578, cstc2021jcyj-msxmX0610]; Rehabilitation Medicine of Southwest University; Key Disciplines of Traditional Chinese Medicine of Chongqing City [2021-4322190044]
基金资助正文：This study is supported by National Natural Science Foundation of China (No. 81873034, 81801329) , Chongqing Natural Science Foundation (No. CSTB2022NSCQ-MSX1578, cstc2021jcyj-msxmX0610) , Grant from Rehabilitation Medicine of Southwest University, Key Disciplines of Traditional Chinese Medicine of Chongqing City (2021-4322190044) .
