Geraniin Protects against Cerebral Ischemia/Reperfusion Injury by Suppressing Oxidative Stress and Neuronal Apoptosis via Regulation of the Nrf2/HO-1 Pathway.

Yuan Yang,Bo He,Rui Li,Xin Xia,Zhiqiang Shen,Peng Chen,Xiaochao Zhang,Lu Chen,Renhua Yang,Vladimir Jakovljevic

doi:10.1155/2022/2152746

Abstract

Geraniin, a polyphenol isolated from Phyllanthus amarus, possesses extensive biological and pharmaceutical activities. In this study, we investigated the protective effect against cerebral ischemia/reperfusion (I/R) injury of geraniin and explored its potential mechanism. Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to simulate cerebral I/R injury in vivo, and oxygen-glucose deprivation/reoxygenation (OGD/R) was applied to establish an in vitro model of cerebral I/R injury. In this study, we performed TTC and HE staining and adopted a neurological score method to evaluate the neuroprotective effect of geraniin in vivo and used the CCK-8 assay to assess this effect in vitro. Indices of reactive oxidation capacity were measured in vivo and in vitro to verify the antioxidant capacity of geraniin. TUNEL staining and flow cytometry were applied to measure the apoptosis rate, and Western blotting was performed to assess the expression of apoptosis-related proteins. Finally, the expression of Nrf2 and HO-1 was evaluated in vivo and in vitro by Western blotting. Geraniin significantly reduced the infarct volume, decreased neurological deficit scores, alleviated pathological changes in neurons, and increased the cell survival rate. Geraniin increased the activity of superoxide dismutase (SOD) and decreased the activity of lactate dehydrogenase (LDH) and the contents of malondialdehyde (MDA), nitric oxide (NO), and neuronal nitric oxide synthase (nNOS) in vivo and in vitro. In addition, geraniin significantly reduced the apoptosis. Furthermore, geraniin also evidently increased Nrf2 (total and nuclear) and HO-1 protein expression in vivo and in vitro. Collectively, these results imply that geraniin may exert a protective effect against cerebral I/R injury by suppressing oxidative stress and neuronal apoptosis. The mechanism underlying the protective effect of geraniin is associated with activation of the Nrf2/HO-1 pathway. Our results indicate that geraniin may be a potential drug candidate for the treatment of ischemic stroke.

Highlights

Stroke, a common cerebrovascular disease in the clinic, can be divided into ischemic and hemorrhagic stroke and remains the predominant cause of death and disability in both developed and developing countries [1]
The number of surviving neurons was significantly increased in the geraniin- (20 mg/kg) and nimodipine- (1 mg/kg) treated groups compared with the Middle cerebral artery occlusion/reperfusion (MCAO/R) group
These results indicated that geraniin protects against I/R injury in rats in vivo

Summary

Introduction

A common cerebrovascular disease in the clinic, can be divided into ischemic and hemorrhagic stroke and remains the predominant cause of death and disability in both developed and developing countries [1]. Ischemic stroke, which is caused by sudden interruption of blood flow to the brain, resulting in brain cell death and neurological impairment, is the most prevalent type of stroke and accounts for approximately 75% of all stroke cases [2]. Early restoration of blood supply after ischemic stroke is considered the main treatment strategy for improving clinical outcomes. Much progress has been made in the study of the mechanism underlying cerebral I/ R injury in recent years, the pathogenesis of the disease is still not fully elucidated, and there is a lack of effective treatments [4].

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