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

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.

YiQiFuMai Powder Injection Protects against Ischemic Stroke via Inhibiting Neuronal Apoptosis and PKCδ/Drp1‐Mediated Excessive Mitochondrial Fission

“…Aberrant mitochondrial dynamics play critical roles in the pathological processes of ischemic stroke [ 14 ]. Previous studies have shown that YQFM protects against myocardial ischemia/reperfusion injury via AMPK pathway mediated mitochondrial fission [ 39 ] and oxygen-glucose deprivation-induced PC12 cell apoptosis through ER stress [ 36 ]. However, the effects of YQFM against mitochondrial dysfunction and excessive fission induced by ischemic stroke have not been fully elucidated.…”

“…Rg1 prevents myocardial hypoxia/reoxygenation injury by regulating mitochondrial dynamics imbalance [ 35 ]. Recent studies have also indicated that YQFM protects against ischemic injury through regulating endoplasmic reticulum stress-mediated neuronal damage [ 36 ]. YQFM also ameliorates blood-brain barrier (BBB) dysfunction through NF- κ B and ROCK1/MLC signaling pathways [ 37 , 38 ].…”

Ruscogenin Attenuates Cerebral Ischemia-Induced Blood-Brain Barrier Dysfunction by Suppressing TXNIP/NLRP3 Inflammasome Activation and the MAPK Pathway

“…Western blotting analysis was performed as reported previously [ 54 ]. In brief, the brain tissues or cells were lysed and centrifuged at 12,000× g for 10 min at 4 °C.…”

Mitochondrial MPTP: A Novel Target of Ethnomedicine for Stroke Treatment by Apoptosis Inhibition

“…As a prescription commonly used in Tibetan medicine to treat ischemic sequelae, our research group proved that the anti-cerebral ischemia effect of ErShiWei ChenXiang pills may be related to its regulation of Bcl-2 family, inhibition of apoptosis, and increase of energy supply (Hou et al, 2020). While regulating Bcl-2 family members, AnNao tablets (Zhang et al, 2020) and YiQi FuMai powder injection (Cao et al, 2016; may also be involved in inflammation and mitochondrial autophagy to maintain mitochondrial MMP and energy production. In addition, both TongXinLuo's regulation of AKT/ERK signaling (Yu et al, 2016;Cheng et al, 2017) and XingNaoJing injection's regulation of the PI3K-AKT pathway ultimately contributed to the regulation of Bcl-2 and the inhibition of ischemic neuron apoptosis.…”