Neuroprotective effects of germacrone on rats with ischemic stroke
Objective To study the protective effects and possible mechanism of germacrone on rats with ischemic stroke and on neuron damage caused by oxygen-glucose deprivation.Methods SD rats were randomized into sham-operated group(an equal volume of saline),model group(an equal volume of saline),positive drug group(nimodipine,10 mg/kg),and low-(5 mg/kg),medium-(10 mg/kg),and high-dose(20 mg/kg)germacrone groups,with 20 rats in each group.The ischemic stroke rat model was prepared by the thread embolism method,and each drug group was injected intraperitoneally with the corresponding drug once at 1.5 h post-ischemia.Postoperative measurements at 24 hours for each group of rats included brain index,brain tissue water content,neurological function score,hippocampal tissue morphology,and cysteine aspartic acid specific protease-3(Caspase-3)activity and apoptosis levels in the brain tissue.The serum levels of oxidative stress factors,including superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px),as well as those of inflammatory factors,including tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)were all measured.Primary rat neurons were divided into control group,model group,positive drug group(nimodipine,1 μmol/L),and low-(50 μmol/L),medium-(100 μmol/L),and high-dose(200 μmol/L)germa-crone groups.After 24 h of cell pre-treatment,the cells in all groups were subjected to oxygen-glucose deprivation and reglucose-reoxygenation except the control group.After the experiment,the survival rate,Caspase-3 activity,and apoptosis of cells were measured in each group.Results Compared with the sham-operated group,the model group exhibited increased brain index,brain tissue water content,and neurological function score(P＜0.05 or P＜0.01);the serum levels of inflammatory factors TNF-α,IL-6,and IL-1 β were elevated(P＜0.01);the serum levels of oxidative stress factors SOD and GSH-Px were reduced(P＜0.01),while that of MDA increased(P＜0.01);Caspase-3 activity was higher(P＜0.01),and the neurons showed typical necrotic features with an increased apoptosis rate(P＜0.01).Compared with the model group,the positive drug group and the various germacrone dose groups exhibited decreased brain index,brain tissue water content,and neurological function scores(P＜0.05 or P＜0.01),decreased levels of inflammatory factors TNF-α,IL-6,and IL-1 β in the serum(P＜0.05 or P＜0.01),increased levels of oxidative stress factors SOD and GSH-Px(P＜0.05 or P＜0.01),decreased MDA level(P＜0.05 or P＜0.01),as well as reduced Caspase-3 activity and apoptosis rate(P＜0.05 or P＜0.01).The experiment of the primary rat neurons revealed that,compared with the control group,cells in the model group showed significantly reduced survival rate(P＜0.01),with increased Caspase-3 activity and apoptosis rates(P＜0.01);compared with the model group,cells in the positive drug group and various germacrone dose groups showed significantly higher survival rate(P＜0.01),and lower Caspase-3 activity and apoptosis rates(P＜0.05 or P＜0.01).Conclusion Germacrone has a significantly ameliorative effect on the injury of rats with ischemic stroke and neuron damage caused by oxygen-glucose deprivation,and its mechanism may be related to the inhibition of neuronal apoptosis.
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