Repair Impacts Of Acanthopanax Senticosus Against Radiation Induced Brain Injury In Mice Model

A large number of studies have shown that natural-based medicines,compared with chemical-based drugs,are gaining acceptance as countermeasures against radiation injury because of their superior characteristics,specifically low toxicity and multi-target effects.In this article,Traditional Chinese Medicine,Acanthopanax senticosus(AS)was the plant material.60Co-? ray was applied to the mice head to simulate the biological effects of radiation on the central nervous system(CNS).By using vivo experiments to study the recover effects of AS on brain damage which caused by radiation and its intrinsic mechanism.(1)The results of pharmacokinetics analysis showed that active compounds in AS had different pharmacokinetic characteristics in mice model.Cmax and AUC of Acanthopanax senticosus polysaccharide(ASPS)were significantly reduced in radiation-injured mice,suggesting that blood flow of mice was blocked or slowed due to the pathological state of ischemia and hypoxia which cause by radiation.On the contrast,the ability of various metabolizing enzymes inactivation,capacity of biofilm transport decrease and lessen of renal blood flow account for radiation,resulting in the accumulation of syringin and elentheroside E in the mice model.Therefore,there were higher pharmacokinetic parameters-AUC,MRT and t1/2 of the two compounds in radiation group compared with normal group.(2)The repair impacts of AS,on behavior and oxidation indexes of irradiated mice were explored by Morris Water Maze(MWM)Test,Sucrose Preference Test(SPT),pathological sections and antioxidant indexes.We testified that AS could protect the mice's immune organs from the invasion of adverse environment.Through increasing the ability of superoxide dismutase(SOD),glutathione(GSH)and catalase(CAT),decreasing the content of malondialdehyde(MDA)and the ability of lactic dehydrogenase(LDH)in mice serum,we testified that AS had the ability to protect mice from oxidative damage induced by 60Co-? ray and remove free radicals in their serum for maintaining normal physiological function of mice and repairing radiation damage.Behavioral experiments showed that AS had positive effects on the spatial memory,learning ability and central nervous system sensitivity of radiation-injured mice.At the same time,pathological sections of brain tissue also illustrated that the AS could effectively control irradiated mice's nerve cell swelling,protein loss,and necrotic tissue liquefaction dissolved in their brain tissue.(3)Then,in order to investigate the intrinsic mechanism of AS on radiation injury,AS extract's protection effects on brain which suffered from radiation were explored.Metabolomics data demonstrated that treatment with AS extract resulted in significantquantitative changes of 16 classes of cerebral metabolites in the prefrontal cortex(PFC)of irradiated mice.Using principal component analysis(PCA),three principal components-F1,F2 and F3 were identified as related to brain energy metabolism,brain tissue development,and brain glutamate cycle,respectively.And the F2 and F3 scores of the AS-treated group of mice were higher compared to mice that were treated with positive control-Venlafaxine.Especially the efficiency of balancing the glutamate cycle that the former achieved was double compared to that in latter.This experiment also found that AS could reduce the anaerobic respiration in the brain of mice,prevent the acidic cell environment caused by lactic(Lac),thereby inhibiting the invasion and metastasis of cancer cells.While providing the necessary energy for mice brain to maintain their normal physiological function.AS had the ability of promoting mice brain tissue development,preventing radiation induced abnormalities of mice brain tissue from interstitial fluid extravasation,maintaining their physiological function of brain neurons and biofilm by increasing the content of taurine(Tau),N-acetyl aspartate(NAA)and acetate(Ace)in mice's PFC.AS could also increase the contents of Glutamine/Glutamate(Glx),and down-regulate the content of ?-aminobutyric acid(GABA),therefore alleviating the phenomenon of lethargy after radiation and restoring their physiological activity.(4)At the same time,the total proteins expression in PFC of each mice group were analyzed by using two-dimensional electrophoresis(2-DE).The proteomic results showed that,the activities of AS in repressing expression changes of radiation response proteins in PFC of mice brain including 14-3-3 protein family(14-3-3?,?),tubulin protein family(tubulin-?,?),Heat shock protein 90-?(HSP 90?),dihydropyrimidinase related protein 2(CRMP2),?-actin,and Enolase 2.The results demonstrated the AS extract had a positive effects on nerve cells' structure,adhesion,locomotion,fission and phagocytosis.Through regulating various action pathways such as Hippo,Phagosome,P13K-AKt,Neurotrophin,Rap1,Gap junction,Glycolysis and HIF-1 signaling pathways to maintain mice's normal neurological activity and prevent their brain damage even cancer caused by radiation.Taken together,all the experimental results showed that AS could be multi-channel,multi-target on repairing brain radiation injury,which may be a promising alternative medicine for the treatment of radiation injury in the brain.