Protective Effects Of Ocotillol On Focal Cerebral Ischemic Injury In Rats

Objective Ischemic cerebrovascular disease(ICVD)is an usually pathologic process and influence human health and life badly.At present cerebrovascular disease has become one of these diseases that can cause the serious complications,lingering effects and so much as cause death all over the world.It is very important to research the mechanism of cerebrovascular disease and look for the efficacious drugs actively. As we know,today the therapy of thrombolysis and brain protection is still two major treatments for ischemic cerebrovascular disease.Up to now,traditional Chinese medicines have been paid more and more attention because of the good curative effects in the treatment of the ischemic cerebrovascular diseases.The ginseng root has been used for over 2000 years,in the belief that it is a panacea and promotes longevity.There are extensive literatures on the beneficial effects of ginseng and its constituents.As described in Chinese traditional medicine textbooks,its effectiveness reaches mythical proportions.It is an herb with many active components,and there is evidence from numerous studies that ginseng does have beneficial effects.Contituents in most ginseng species include ginsenosides, polysaccharides,peptides,polyacetylenic alcohols,and fatty acids.Most pharmacological actions of ginseng are attributed to ginsenosides,a diverse group of steroidal saponins,which demonstrate the ability to target a myriad of tissues, producing an array of pharmacological responses.At present,pharmacological effects of ginseng have been demonstrated in the CNS and in cardiovascular,endocrine,and immune systems.In addition,ginseng and its constituents have been ascribed antineoplastic,antistress,and antioxidant activity.Results of several studies show that 20(S)-Ginsenoside Rg₃ has neuroprotective effects in animal models of focal cerebral ischemia,and plays a major role in the protection of mitochondria in cerebral ischemia rat brain.Studies in vitro also show that ginsenosides may modulate nerve transmission by decreasing the availability of neurotransmitters.Kim et al demonstrated that a single ginsenoside can protect cultured rat cortical cells from glutamate-induced neurodegeneration,and inhibit NMDA receptor-mediated signals in rat hippocampal neurons.Ocotillol is a ginsenoside-derivate in gastrointestinal tract in vivo or alkaline degradation product from ginsenoside F₁₁in vitro.The present study aimed to investigate whether ocotillol,a derivate of pseudoginsenoside E₁₁,has protective effects on brain injury after focal cerebral ischemia and to approach the possible mechanism.In the experiment,we estimate the behavioral tests,the infarction area of brain,histopathologic changes of ischemic brain tissue,and activities of superoxide dismutase(SOD),total antioxidative capability(T-AOC),glutathione peroxidase (GSH-Px),and malonaldehyde(MDA)level in brain homogenate and serum.Methods Two hundred and fourty adult male Wistar rats were used in the experiment. After fed for a week,animals were randomly divided into eight groups:sham group, ischemia group,nimodipine group,as well as five ocotillol groups,to which ocotillol was administered at the dose of 1.25,2.5,5,10,20 mg·kg^-1,respectively.Nimodipine was given at a dose of 6 mg·kg^-1as reference control.The solution was administered orally at 5 mL·kg^-1in each animal,while the sham or ischemia animals received the same volume of 0.5%CMC-Na once a day.The treatments were carried out just 7 days prior to the occlusion.At the seventh day,one hour after administration,middle cerebral artery occlusion(MCAO)was used to induce focal cerebral ischemia.12 hours later,behavioral tests were used to evaluate the damage to central nervous system which were determined with a 0-4 grade scale.The infarction area of brain was assessed in brain slices stained with 2%solution of 2,3,5-triphenyl tetrazolium chloride(TTC)and quantitated by image analysis system.Histopathologic changes of ischemic brain tissue were obseved with hematoxylin and eosin stain.Activities of superoxide dismutase(SOD),total antioxidative capability(T-AOC),glutathione peroxidase(GSH-Px),and malonaldehyde(MDA)levels of brain homogenate and serum were measured by biochemical methods to evaluate the antioxidant effects.Results Compared with the sham group,neurological deficit scores and infarction area in ischemia animals significantly increased.Cerebral histopathological slides showed degenerative changes.And MDA level in ischemia rats significantly increased while SOD,T-AOC,GSH-Px activities decreased markedly in comparsion with the sham group.Compared with the ischemia group,ocotillol pretreatment,especially at the dose of 5 mg·kg^-1could significantly decrease neurological deficit scores,reduce the percentage of infarction area,and alleviate the histopathological changes in the ischemic cerebral hemisphere.Furthermore,ocotillol treatment could significantly ameliorate lipid peroxidation by attenuating both the elevation of MDA content and the decreases in SOD,T-AOC,GSH-Px activities in the ipsilateral hemisphere and serum.Conclusion The findings suggests that pretreatment with ocotillol might provide neuroprotective effects on rats which encountered cerebral ischemia through its antioxidant action.