Effect of Chaihu Jia Longgu Mulitang on Signaling Pathway of PI3K/Akt/GSK3β/β-catenin in Hippocampus Tissue of Rats with Depression / 中国实验方剂学杂志
Chinese Journal of Experimental Traditional Medical Formulae
; (24): 12-19, 2020.
Article
in Zh
| WPRIM
| ID: wpr-872693
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WPRO
ABSTRACT
Objective:To study the effect of Chaihu Jia Longgu Mulitang on phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway of hippocampus in rats with depression. Method:A total of 120 SD rats were randomly divided into normal group,model group, and low, middle and high-dose Chaihu Jia Longgu Mulitang groups(3.25,6.5,13 g·kg-1), and fluoxetine group, with 20 rats in each group. Except normal group, the depression model was prepared through chronic unpredictable mild stimulation(CUMS). The normal group and the model group were given normal saline with 6.5 g·kg-1 by gavage. Chaihu Jia Longgu Mulitang groups were intragastrically given corresponding herbal drugs 3.75,6.5,13 g·kg-1, while fluoxetine group was intragastrically given fluoxetine 10 mg·kg-1 for 21 days, once a day. Then the depressive behaviors of rats were observed by sucrose preference test (SPT) and forced swimming test (FST). Western blot was used to detect the protein expressions of PI3K,Akt,GSK3β and phosphorylation level. Result:Compared with normal group,the sucrose preference index was decreased significantly,while the immobility time in FST was increased significantly(P<0.01), the protein expressions of PI3K, p-PI3K p110, p-PI3K p85 were decreased significantly (P<0.01), and expressions of Akt, p-Akt Thr308,p-Akt Ser473, p-GSK3β Ser9 and β-catenin were decreased significantly(P<0.01), while the level of GSK3β, p-GSK3β Tyr216 were increased significantly in model group(P<0.05,P<0.01). Compared with model group,Chaihu Jia Longgu Mulitang could increase sucrose preference index and decrease the immobility time in FST(P<0.01), the protein expressions of PI3K p110 and PI3K p85 was increased significantly (P<0.01), levels of Akt Thr308,Akt Ser473, p-GSK3β Ser9, β-catenin were increased significantly (P<0.01), whereas levels of GSK3β, and GSK3β Tyr216 were decreased significantly. Conclusion:Chaihu Jia Longgu Mulitang could increase protein expression and activity of PI3K in rat hippocampus, activate Akt, inhibit GSK3β kinase activity and prevent β-catenin from degradation, so as to increase PI3K/Akt pathway activity in rat hippocampus, and protect hippocampal neurons.
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WPRIM
Language:
Zh
Journal:
Chinese Journal of Experimental Traditional Medical Formulae
Year:
2020
Type:
Article