Abstract

The present study was designed to investigate the protective effect of eriodictyol on MCAO-induced brain injury and its regulation of neural function and to explore the mechanism of its regulation of autophagy in rats. Brain injury was induced by middle cerebral artery occlusion (MCAO) in adult rats and pretreated with eriodictyol (low dose: 20 mg/kg; medium dose: 40 mg/kg; high dose: 80 mg/kg) or saline. Rats in the treatment group had a smaller volume of infarction and improved neurological outcome and reduced the latency to the platform, increased the time spent in the correct quadrant compared to MCAO rats pretreated with saline. ELISA kits results confirmed that eriodictyol reduced the inflammatory response induced by MCAO. The results of apoptosis and proliferation by Nissl staining and immunofluorescence detection indicated that eriodictyol could inhibit apoptosis and promote the proliferation in MCAO rats. The expressions of LC3, ATG5, p62, and Beclin1 were used to evaluate the autophagy, as well as the reversal of the autophagy activator (rapamycin) on the neuroprotective effect of eriodictyol, which suggested that the protective effect of eriodictyol on brain injury may be related to the inhibition of autophagy. In summary, we, therefore, suggested that eriodictyol could reduce the inflammation response of brain injury and inhibit neuroapoptosis, directly affecting autophagy to alleviate brain injury. It will provide theoretical support for eriodictyol in the treatment of ischemic stroke.

Highlights

  • Ischemic brain injury is associated with extremely high rates of disability and mortality around the world

  • To observe the effect of eriodictyol against middle cerebral artery occlusion (MCAO)-induced brain injury, rats were treated with different doses of eriodictyol for 14 days before MCAO (Supplementary Figure 1)

  • Brain infarct volume was measured at 24 h after MCAO (Figures 1B,C) by tetrazolium chloride (TTC) staining

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Summary

Introduction

Ischemic brain injury is associated with extremely high rates of disability and mortality around the world. Stroke is a fatal medical condition in which broken or blocked blood vessels that suddenly prevent blood to flow to the brain, starving the tissue of oxygen and glucose. Ischemic stroke is considered to be one of the major fatal diseases with high morbidity, mortality, and disability rate in the world (Mavroudakis et al, 2020). Stroke is the leading cause of death among residents worldwide and is expected to increase by 24.9% by 2030 (from 2010; Chavda et al, 2021). There are few therapeutic strategies for ischemic stroke, and the commonly used and effective treatment. Prevention of stroke and post-ischemia-reperfusion injury repair remains an urgent and unmet need

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