Fraxetin protects rat brains from the cerebral stroke via promoting angiogenesis and activating PI3K/Akt pathway

Abstract

Objective

Fraxetin has antioxidant, anti-inflammation and neuroprotective functions, however, its role in ischemic stroke is still vague. Herein, this study delves into the underlying mechanism.

Methods

Ischemia and reperfusion operation were performed to establish the cerebral stroke rat models. The brain functions were evaluated with neurological score. The brain infarcted volume in fraxetin group was measured by 2,3,5-triphenyltetrazolium chloride staining. The blood-brain barrier permeability, CD34 enrichment, and the brain water content were measured by Evans blue staining, immunofluorescence staining, and wet-dry method, respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) were applied to examine the levels of angiogenesis- and PI3K/Akt pathway-related factors. MTT and tube formation assays were used to measure the viability and tube formation of HUVECs.

Results

Fraxetin decreased the brain injury-related neurological score, brain infarction, and cerebral edema and maintained blood-brain barrier permeability, whereas it promoted the angiogenesis in ischemia-damaged brain via enhancing CD34 enrichment, the expressions of VEGF, Ang-1, Tie-2, and CD-31, viability of HUVECs, as well as activating the phosphorylation of PI3K and Akt. Importantly, wortmannin (a specific PI3K inhibitor) impeded the fraxetin-induced cell viability, angiogenesis, and phosphorylation of Akt and PI3K in HUVECs.

Conclusions

Fraxetin has protective effects on the brain ischemia-reperfusion injury and promotes angiogenesis for cerebral repair via phosphorylation of PI3K and Akt.

Keywords:

• Fraxetin
• cerebral stroke
• angiogenesis
• PI3K
• Akt

Ethics statement

The procedures were approved by the Animal Ethics Committee of Nanfang Hospital (IR201811045).

Disclosure statement

The authors declare no conflicts of interest.

Substantial contributions to conception and design: Y Cui.

Data acquisition, data analysis, and interpretation: M Liu, L Zuo, H Wang, J Liu.

Drafting the article or critically revising it for important intellectual content: Y Cui.

Final approval of the version to be published: All authors.

Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: All authors.

Data availability statement

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the 2020 Medical Science Research Project Plan of Hebei Provincial Health Commission [20200560]; the 2018 Zhangjiakou Science and Technology Bureau Project [1821042D].