| Depression(depressive disorders)is a common mental disorder,with essential features are depressed mood,retardation of thinking,enthusiasm decline,cognitive dysfunction and so on.Depression also cause such as sleep disorders,fatigue,loss of appetite,weight loss and other physical symptoms.Its incidence rate exhibited a gradually rising tendency,to improve the treatment of depression has gained considerable interest of psychiatry and many other disciplines.Drug therapy is the main therapy of depression.But considering that depression is a complex disease involving multiple mechanisms,there is still no ideal drug.Even lower toxicity and few side effects,the low response rate and the long-term use may still cause potential adverse reactions with the novel antidepressants.Thus it remains urgent to do further investigate the pathogenesis of depressive disorder,and develop novel antidepressants.Xylariasp is the fungus sclerotia which grown in termite nests,and its medicinal properties includes diuresis,filling the mind,to treat insomnia,vomiting blood and postpartum bleeding treatment.Wuling powder is light brown to brown powder,which is made by cultivating Xylariasp mycelium using submerged fermentation technology.The capsule preparation of Wuling powder is mainly used to soothe nerves and anti-insomnia in clinical.The antidepressant and anti-anxiety effect of Wuling powder has been confirmed in clinical,which indicated the unique advantage of Chinese medicine.In order to prove this advantage,further researches on the mechanism are still needed.In this study,we established social defeat stress animal model of depression in mice,observed the antidepressant effect of Wuling powder by social avoidance test.The results showed that the ratio of time of model mice spent in the interaction zone with the presence of a target CD-1 compared with the absence of a target CD-1 was obviously decreased(P<0.01).After treatment with Wuling powder,the ratio was ameliorated observably(P<0.05).In addition,the ratio of time of model mice spent in the corner zone in the presence of a target CD-1 compared with the absence of a target CD-1 was significantly increased(P<0.01),and treatment with Wuling powder dramatically decreased this ratio(P<0.05).Further we explored the mechanism of antidepressant effect of Wuling powder.The expression level of endoplasmic reticulum stress-related genes and proteins was detected by Western-blotting and real-time quantitative PCR.Results showed that Wuling powder treatment significantly attenuated the up-regulation of GRP78,PDI protein expressions which induced by social defeat stress(P<0.05).The up-regulation of IREla and sXBPl were observed in model mice(P<0.05),while Wuling powder decreased their expression level significantly(P<0.05).Meanwhile,results showed that model mice experienced increased the level of P-eIF2a and ATF4 expression(P<0.05),and Wuling powder was capable of alleviating the impact(P<0.05).We also found that Wuling treatment significantly decreased the apoptosis-related protein or mRNA expression level of CHOP and increased Bcl-2/Bax ratio compared with model group(P<0.05).In conclusion,our results suggested that Wuling powder exhibited a obvious antidepressant effect by effectively maintaining the endoplasmic reticulum homeostasis and protecting the neurons to restore normal cell function.Cerebral ischemia is the second global cerebrovascular disease.Ischemia-reperfusion injury is one of the important pathophysiological mechanisms of cerebral ischemia.Studies have confirmed that cerebral ischemia and reperfusion injury caused extensive mitochondrial progressive injury.Autophagy is a common mechanism for removing damaged mitochondria.The normal physiological activity of the neurons depends on the ATP produced by the mitochondria.Therefore,the normal function of mitochondria plays an important role in injury and repair stage of cerebral ischemia.Currently,one of the clinical treatments for the ischemic stroke is the use of thrombolysis drugs in combination with the neuroprotective drugs.How to reduce reperfusion injury after thrombolytic therapy has become an important issue.So far,there is no effective and safe drug for the treatment of cerebral ischemia rcperfusion injury.Guhong injection is a combination of acetylglutamine and safflower extract.The active ingredient contained in the safflower extract has been confirmed to protect against cerebral ischemia,such as hydroxy safflower yellow A.Acetylglutamate is an acetylated derivative of glutamine.Studies showed that glutamine antagonize neuronal damage caused by cerebral ischemia.Clinical trials have demonstrated that its great clinical value in ameliorateing the neurological function in patients with cerebral infarction.The previous studies of our laboratory also showed that Guhong injection can significantly improve the experimental cerebral ischemia and reperfusion injury in rats.In order to explore its pharmacological mechanism,we established middle cerebral artery occlusion(MCAO)model to evaluate the pharmacodynamics of Guhong injection by neurological deficit score and sticker removal experiment.The results showed that neurological deficit scores were significantly increased(P<0.05)with the total time of bilateral forelimb completely removed the sticker significantly longer(P<0.05)in model rats.Treatment with Guhong injection signicantly reduced neurological deficit score and shortened the time of removal-test(P<0.05).The western-blotting results demonstrated that the expression of Beclinl,Parkin,KIFC2 and UCP3 protein was up-regulated by Guhong injection significantly(P<0.05).Overall,we observed that Guhong injection has a significant protective effect on cerebral ischemia-reperfusion injury in rats,and this effect may be achieved through the protection of mitochondrial function.This provides a new theoretical basis for the clinical application of Guhong injection,also provides new ideas for the development of new drugs against cerebral ischemia. |
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