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Objective @#To investigate the effects of cynomorium songaricum extract on cognitive dysfunction of Alzheimer disease (AD) model mice based on network pharmacology and animal experiments.@*Methods @#Network pharmacology was used to predict the related targets and signal pathways of the extract of cynomorium songaricum to improve AD. Senescence accelerated mice P8 (SAMP8) were selected as the model of AD. Based on the results of the preliminary experiment , 0. 17 g/(kg ·d) was selected as the optimal dosage for the extract of cynomorium songaricum. The extract of cynomorium songaricum [0. 17 g/(kg ·d) , Donepezil hydrochloride [2. 0 mg/(kg ·d)] and normal saline were given orally for 28 days according to the groups. Morris water maze evaluated the learning and cognitive function of animals. The number of neurons in cornu ammonis 1 (CA1) of hippocampus was ob served by Nissl staining. The expression of recombinant Beclin 1(Beclin ⁃1) , Sequestosome 1 (p62) , light chain 3 (LC⁃ nase (PI3K) , protein kinase B (AKT) and glycogen synthase kinase3β (GSK⁃3β) in the hippocampus of mice in each group were detected by Western blot.@*Results @#Based on the network pharmacology study , it was predicted that the biological mechanism of cynomorium songaricum to improve AD might be the regulation of autophagy , and the possible signaling pathway was PI3K/AKT/GSK⁃3β . The results of animal experiments showed that the extract age of hippocampal neurons , significantly increase the number of neurons , and increase the expression levels of PI3K , p ⁃AKT/AKT , p ⁃GSK⁃3β/GSK⁃3β , B eclin ⁃1 and LC3 in the hippocampus of mice. The expression level of p62 decreased. There was no significant difference between male and female mice during the experiment. @*Conclusion@#The extract may improve the cognitive dysfunction of male and female AD models by activating autophagymediated by PI3K⁃AKT⁃GSK⁃3β signaling pathway , and there is no significant gender difference in the effect.
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@#Objective To observe the effects of metformin on learning and memory ability in Alzheimer’s disease (AD) rats,and to further explore the potential mechanism.Methods Fifty male SD rats were randomly divided into normal group,sham group,model group and treatment group.AD model was established by injecting 5 μl Aβ25-35 (2 g/L) into the hippocampus,and the same amount of normal saline was injected into the sham group rats.The rats in the treatment group were given 100 mg/(kg·d) metformin by gavage for 2 weeks.The next day,the learning and memory ability of rats,the basic conditions of hippocampal cells,and the relative expression levels of PI3K,AKT,P-AKT,GSK3β,P-GSK3β,tau ［PS202］ and tau5 in hippocampal tissues of rats in each group were detected.Results Metformin significantly improved the cognitive ability of AD model rats (P<0.05).No significant difference in the basic morphological structure of hippocampal cells among all groups was observed.Compared with the normal and sham group,the expression levels of PI3K,P-AKT/AKT,P-GSK3β/GSK3β in the hippocampus of the model rats were significantly down-regulated (P<0.05),which were improved after metformin intervention (P<0.05).The expression of tau［pS202］/tau5 in the model group was significantly higher than that in the normal group and the sham group,and the phosphorylation of tau protein decreased after treatment (P<0.05).Conclusion Metformin can effectively improve the learning and memory ability of AD model rats.Interestingly,the mechanism may be closely related to the “PI3K-AKT-GSK3β-tau phosphorylation” signaling pathway.
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OBJECTIVE: To investigate the anti-hepatocellular carcinoma effect and underlying mechanisms. METHODS: In PLC/PRF/5 and HepG2, after treatment with Grifola frondosa extract, MTT method, chemical method, JC-1 staining and Western Blot were applied to determine cell viability, caspase 3 activity, mitochondrial membrane potential, the expression of Bcl-2 and Bax, and the phosphorylation of Akt/GSK3β. The anti-tumor activity of Grifola frondosa extract was further confirmed in PLC/PRL/5-xengrafted mice model. RESULTS: Grifola frondosa extract significantly reduced cell viability, mitochondrial membrane potential, the expression of Bcl-2 and the phosphorylation of Akt/GSK3β, and enhanced LDH release, caspase 3 activity and the expression of Bax in both PLC/PRF/5 and HepG2 cells. 12-day Grifola frondosa extract treatment significantly inhibited the PLC/PRF/5-xenografted tumor growth without influence the body weight of mouse. CONCLUSION: All these data indicate that Grifola frondosa extract-mediated anti-hepatocellular carcinoma effects are related to its modulation of the activations of Akt/GSK3β and mitochondrial pathway.