Shengmai injection attenuates the cerebral ischemia/reperfusion induced autophagy via modulation of the AMPK, mTOR and JNK pathways

Abstract

Context Shengmai injection (SMI) is a patented Chinese medicine originated from the ancient Chinese herbal compound Shengmai san, which is used extensively for the treatment of cardiovascular and cerebrovascular disease in the clinic.Objective To determine the neuroprotective effect of SMI, we investigated the effect of SMI on cerebral ischemia/reperfusion (I/R) injury in mice as well as the mechanisms underlying this effect.Materials and methods Right middle cerebral artery was occluded by inserting a thread through internal carotid artery for 1 h, and then reperfused for 24 h in mice. The neuroprotective effects were determined using transmission electron microscopic examination, the evaluation of infarct volume, neurological deficits and water brain content. Related mechanisms were evaluated by immunofluorescence staining and western blotting. SMI was injected intraperitoneally after 1 h of ischemia at doses of 1.42, 2.84 and 5.68 g/kg. The control group received saline as the SMI vehicle.Results Results showed that SMI (1.42, 2.84 and 5.68 g/kg) could significantly reduce the infarct volume, SMI (5.68 g/kg) could also significantly improve the neurological deficits, decreased brain water content, as well as the neuronal morphological changes. SMI (5.68g/kg) could significantly inhibit the expression of autophagy-related proteins: Beclin1 and LC3. It also reduced the increase in LC3-positive cells. SMI (5.68 g/kg) remarkably inhibited the phosphorylation of adenosine monophosphate activated protein kinase (AMPK), and down-regulated the phosphorylation of mammalian target of rapamycin (mTOR) and Jun N-terminal kinase (JNK) after 24 h of reperfusion.Discussion and conclusion The results indicate that SMI provides remarkable protection against cerebral ischemia/reperfusion injury, which may be partly due to the inhibition of autophagy and related signalling pathways.