Bioactive Flavonoids Icaritin and Icariin Protect against Cerebral Ischemia-Reperfusion-Associated Apoptosis and Extracellular Matrix Accumulation in an Ischemic Stroke Mouse Model.

Cheng-Tien Wu,Ting-Hua Yang,Chang-Mu Chen,Man-Chih Chen,Lin-Hwa Long,Siao-Syun Guan,Shing-Hwa Liu

doi:10.3390/biomedicines9111719

Abstract

Stroke, which is the second leading cause of mortality in the world, is urgently needed to explore the medical strategies for ischemic stroke treatment. Both icariin (ICA) and icaritin (ICT) are the major active flavonoids extracted from Herba epimedii that have been regarded as the neuroprotective agents in disease models. In this study, we aimed to investigate and compare the neuroprotective effects of ICA and ICT in a middle cerebral artery occlusion (MCAO) mouse model. Male ICR mice were pretreated with both ICA and ICT, which ameliorated body weight loss, neurological injury, infarct volume, and pathological change in acute ischemic stroke mice. Furthermore, administration of both ICA and ICT could also protect against neuronal cell apoptotic death, oxidative and nitrosative stress, lipid peroxidation, and extracellular matrix (ECM) accumulation in the brains. The neuroprotective effects of ICT are slightly better than that of ICA in acute cerebral ischemic stroke mice. These results suggest that pretreatment with both ICA and ICT improves the neuronal cell apoptosis and responses of oxidative/nitrosative stress and counteracts the ECM accumulation in the brains of acute cerebral ischemic stroke mice. Both ICA and ICT treatment may serve as a useful therapeutic strategy for acute ischemic stroke.

Highlights

We first observed the effects of these drugs on the brain pathological changes and neuronal function loss in middle cerebral artery occlusion (MCAO) mice
We examined the effects of ICA and ICT on endothelial–mesenchymal transition in the brains of MCAO mice
Our results revealed that both ICA and ICT administered by intraperitoneal injection at a dose of 60 mg/kg effectively improved brain injury in acute cerebral ischemic stroke mice

Summary

Introduction

According to the statistic report of the World Health Organization (WHO), stroke is the second leading cause of mortality in the world [1]. The health care disbursements spent on stroke have been estimated to be approximately 3% to 4% of total expenditures in many countries [2]. The death rates and prevalence of stroke have reduced over time, the medical burden or substantially rehabilitative economic costs for post-stroke care remain likely to become a heavy load of many countries [3].

Objectives

Methods

Results

Discussion

Conclusion