The Neuroprotective Effects And The Related Mechanism Of Moringa Oleifera Seeds Ethanol Extract On Ischemic Stroke

Background:Stroke is a kind of common cerebral vascular disease with neurological deficits.Patients with strok often suffer from cognitive impairment and other chronic ischemic brain damage.If cognitive impairment is not controled,the stroke patients can easily develop into dementia.At present,there are no effectivly therapeutic drugs for chronic cerebral ischemia injury.Therefore,it is of great significance to study and search for drugs that can improve cognitive impairment of cerebral ischemia.Moringa oleifera is a new type of medicinal and dual-purpose plant that has many pharmacological effects including neuroprotective effects.In the previous experimental studies in our laboratory,the results have confirmed that moringa oleifera seeds ethanol extract(MSE)can improve scopolamine-induced dysfunction of learning and memory in mice.However,the neuroprotective effect of moringa seeds ethanol extract on stroke is not clear,so this paper will conduct a study to solve this issue.Research purposes:To investigate the effect of MSE on neuroprotection and mitigating cognitive dysfunction after stroke.Research methods:The middle cerebral artery occlusion(MCAO)was used to construct the right temporal focal cerebral ischemia model.In the acute phase experiment,to investigate their preprotective effects,different doses of MSE(125 mg/kg,250 mg/kg,500 mg/kg)were pre-protected in mice after ischemia for 3 days.In order to determine the possible therapeutic window,then MSE(500 mg/kg)was administered as a single dose at Oh,2h or 4 h after reperfusion;In the chronic phase experiment:to determine the effect of MSE on cognitive dysfunction in ischemic stroke,rats after ischemia were given intraperitoneal injection of BrdU(50mg/kg)for 7 days,and simultaneous administration of MSE(400mg/kg).On the 21st day after stroke,a 7-day water maze test was performed to evaluate the learning and memory abilities.Double immunofluorescence staining was applied to test BrdU+/NeuN+ and BrdU+/GFAP+ at 28 day after ischemia.Western Blot and RT-PCR were proceeded to test the protein expression and gene expression of GAP-43/SYP,NGF/NT3/BDNF,SOD,IL-6/IL-10 and Bax/Bcl-2 at 28 days after ischemia.Meanwhile,the activity of ACh/AchE in the hippocampus was tested.Experimental results:1.MSE has a preprotective and therapeutic effect on acute stroke,the best effective dose is 5OOmg/kg,and the best treatment time is at 2h after reperfusion.2.The number of newborn neurons is increased in the ischemic hippocampus after the administration of MSE by promoting the expression of synaptic plasticity(GAP-43,SYP)and neurotrophic factors(BDNF,NGF,and NT3).Also MSE can mitigate cognitive dysfunction and exert prominent neurogenesis promoting effect.3.MSE may improve learning and memory ability by regulating cholinergic system.4.MSE may further produce neuroprotection by inhibiting oxidative stress,inflammatory response and apoptosis induced by ischemic stroke.Conclusion:MSE has a neuroprotective effect,including preprotective and therapeutic effect on acute stroke and alleviating chronic stroke cognitive impairment by promoting neurogenesis and regulating cholinergic system.