Wnt/β-catenin coupled with HIF-1α/VEGF signaling pathways involved in galangin neurovascular unit protection from focal cerebral ischemia.

Abstract

Microenvironmental regulation has become a promising strategy for complex disease treatment. The neurovascular unit (NVU), as the key structural basis to maintain an optimal brain microenvironment, has emerged as a new paradigm to understand the pathology of stroke. In this study, we investigated the effects of galangin, a natural flavonoid isolated from the rhizome of Alpina officinarum Hance, on NVU microenvironment improvement and associated signal pathways in rats impaired by middle cerebral artery occlusion (MCAO). Galangin ameliorated neurological scores, cerebral infarct volume and cerebral edema and reduced the concentration of Evans blue (EB) in brain tissue. NVU ultrastructural changes were also improved by galangin. RT-PCR and western blot revealed that galangin protected NVUs through the Wnt/β-catenin pathway coupled with HIF-1α and vascular endothelial growth factor (VEGF). VEGF and β-catenin could be the key nodes of these two coupled pathways. In conclusion, Galangin might function as an anti-ischemic stroke drug by improving the microenvironment of NVUs.

• Authors: Chuanhong Wu, Jianxin Chen, Chang Chen, Wei Wang, Limei Wen, Kuo Gao, Xiuping Chen, Sihuai Xiong, Huihui Zhao, Shaojing Li
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 16151 (Nov 05 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26537366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Flavonoids
• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit
• Neuroprotective Agents
• Plant Extracts
• Vascular Endothelial Growth Factor A
• beta Catenin
• vascular endothelial growth factor A, rat
• galangin

Topics

• Animals
• Brain (drug effects, metabolism)
• Brain Ischemia (drug therapy, metabolism)
• Flavonoids (pharmacology)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Infarction, Middle Cerebral Artery (drug therapy, metabolism)
• Male
• Neuroprotective Agents (pharmacology)
• Plant Extracts (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Vascular Endothelial Growth Factor A (metabolism)
• Wnt Signaling Pathway (drug effects)
• beta Catenin (metabolism)