Aging
Navigate
Submit an Article
Research Paper|Volume 15, Issue 20|pp 11639—11653

Neurovascular protection of alisol A on cerebral ischemia mice through activating the AKT/GSK3β pathway

Huihong Li1,3, Caiyun Zhang2, Yangjie Zhou3, Yunfei Deng3, Xiaoqing Zheng3, Xiehua Xue1,4
  • 1The Affiliated Rehabilitation Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, China
  • 2The Zhangpu Hospital of Traditional Chinese Medicine, Zhangzhou, Fujian, China
  • 3College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
  • 4Key Laboratory of Cognitive Rehabilitation of Fujian Province, Fuzhou, China
* Equal contribution and share first authorship
Received: March 27, 2023Accepted: October 2, 2023Published: October 26, 2023
https://doi.org/10.18632/aging.205151

Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Alisol A, a triterpene isolated from Alisma Orientale, has been shown to exhibit anti-inflammatory effects and vascular protection. This study was designed to observe the effect of alisol A on cerebral ischemia (CI)-induced neurovascular dysfunction in the hippocampus and to further explore the potential mechanisms. The results showed that alisol A treatment improved the neurological deficits and cognitive impairment of CI mice. Alisol A reduced gliosis and improved neuronal/glial metabolism. Accordingly, alisol A inhibited inflammatory factors IL-6 and IL-1β induced by overactivation of astrocytes and microglia, thus protecting the neurovasculature. Furthermore, alisol A promoted the survival of neurons by decreasing the ratio of Bax/Bcl-2, and protected brain microvascular endothelial cells (BMECs) by upregulating the expression of ZO-1, Occludin and CD31. The phosphorylation of protein kinase B (AKT) and glycogen synthase kinase 3β (GSK3β) increased after treatment with alisol A. To explore the underlying mechanism, AKT was inhibited. As expected, the neurovascular protection of alisol A above was eliminated by AKT inhibition. The present study primarily suggested that alisol A could exert neurovascular protection in the hippocampus of CI mice by activating the AKT/GSK3β pathway and may potentially be used for the treatment of CI.