YiQiFuMai Powder Injection Ameliorates Cerebral Ischemia by Inhibiting Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis.

Guosheng Cao,Yang Hu,Yuwei Han,Jin Qi,Nan Jiang,Yuanyuan Zhang,Boyang Yu,Huana Zhou,Junping Kou

doi:10.1155/2016/5493279

Guosheng Cao, Yang Hu + Show 7 more

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https://doi.org/10.1155/2016/5493279

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Abstract

YiQiFuMai (YQFM) powder injection as a modern preparation derived from Sheng Mai San, a traditional Chinese medicine, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. However, its neuroprotective effect and underlying mechanism in cerebral ischemia remain to be explored. The present study was designed to investigate the neuroprotective effect of YQFM on endoplasmic reticulum (ER) stress-mediated neuronal apoptosis in the permanent middle cerebral artery occlusion- (MCAO-) injured mice and the oxygen-glucose deprivation- (OGD-) induced pheochromocytoma (PC12) cells. The results showed that single administration of YQFM (1.342 g/kg, i.p.) could reduce the brain infarction and improve the neurological deficits and the cerebral blood flow (CBF) after MCAO for 24 h in mice. Moreover, incubation with YQFM (100, 200, and 400 μg/mL) could increase the cell viability, decrease the caspase-3 activity, and inhibit the cell apoptosis in OGD-induced PC12 cells for 12 h. In addition, YQFM treatment could significantly modulate cleaved caspase-3 and Bcl-2 expressions and inhibit the expressions of ER stress-related marker proteins and signaling pathways in vivo and in vitro. In conclusion, our findings provide the first evidence that YQFM ameliorates cerebral ischemic injury linked with modulating ER stress-related signaling pathways, which provided some new insights for its prevention and treatment of cerebral ischemia diseases.

Highlights

Ischemic stroke is a devastating disease that ranks secondly after cardiac ischemia as a cause of death and permanent disability worldwide, estimated by the World Health Organization [1]
cerebral blood flow (CBF) was measured by a laser Doppler flowmetry; the result demonstrated that administration of YQFM at the dosage of 1.342 g/kg resulted in a significant increase on CBF 24 h after MCAO (Figure 1(d)), which indicated that the smaller infarct volume in YQFM-treated groups was correlated with improved CBF during MCAO
We confirmed the neuroprotective effect of YQFM and explored the role of endoplasmic reticulum (ER) stress-mediated neuronal apoptosis in middle cerebral artery occlusion- (MCAO-)injured mice and oxygen-glucose deprivation- (OGD-)injured PC12 cells

Summary

Introduction

Ischemic stroke is a devastating disease that ranks secondly after cardiac ischemia as a cause of death and permanent disability worldwide, estimated by the World Health Organization [1]. Glucose-regulated protein 78 (GRP78) is a main ER molecular chaperone, regulating protein folding and facilitating protein translocation and protein secretion in ER It is widely used as a sentinel marker for ER stress under pathologic conditions [10]. The expressions of ER stress-target genes, such as CHOP and X-box-binding protein-1 (XBP-1), are modulated by an ER-membrane-bound transcription factor, activating transcription factor-6 (ATF-6) [13, 14]. Abundant evidence has shown that the inhibition of all three ER stressrelated pathways and the cell apoptosis exerts a remarkable protective effect on cerebral ischemia and might be a novel and effective treatment after ischemic stroke [8, 15, 16]

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