XQ-1H promotes cerebral angiogenesis via activating PI3K/Akt/GSK3β/β-catenin/VEGF signal in mice exposed to cerebral ischemic injury.

Abstract

Stroke still ranks as a most lethal disease worldwide. Angiogenesis during the chronic phase of ischemic stroke can alleviate ischemic injury and attenuate neurological deficit. XQ-1H is a new compound derived from the structure modification of ginkgolide B, which exerts anti-inflammation and neuroprotection against cerebral ischemic injury during the acute or subacute phase. However, whether XQ-1H facilitates angiogenesis and neural functional recovery during the chronic phase remains unclear. This research was designed to explore whether XQ-1H promotes angiogenesis after ischemic stroke and to preliminarily elucidate the mechanism. In vitro, XQ-1H was found to facilitate proliferation, migration and tube formation in bEnd.3 cells. In vivo, XQ-1H raised the CD31 positive microvessel number and increased focal cerebral blood flow in mice exposed to cerebral ischemic injury, and improved the neurological function. Mechanism studies revealed that XQ-1H exerted angiogenesis promoting effect via the PI3K/Akt/GSK3β/β-catenin/VEGF signal pathway, which was reversed by LY294002 (the specific inhibitor of PI3K/Akt). In conclusion, XQ-1H exerts angiogenetic effect both in vivo and in vitro, which is a potential agent against ischemic stroke during chronic phase.

• Authors: Yuxiang Fei, Bo Zhao, Jianping Zhu, Weirong Fang, Yunman Li
• Journal: Life sciences (Life Sci) Vol. 272 Pg. 119234 (May 01 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33607158 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Ginkgolides
• Lactones
• Vascular Endothelial Growth Factor A
• XQ-1H compound
• beta Catenin
• ginkgolide B
• Glycogen Synthase Kinase 3 beta
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Brain (metabolism)
• Brain Ischemia (drug therapy, metabolism, physiopathology)
• Cerebrovascular Circulation (drug effects)
• China
• Ginkgolides (metabolism, pharmacology)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Infarction, Middle Cerebral Artery (metabolism)
• Lactones (metabolism, pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Microvessels (metabolism)
• Neovascularization, Physiologic (drug effects, physiology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Recovery of Function (drug effects)
• Signal Transduction (drug effects)
• Stroke (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)
• beta Catenin (metabolism)