Effect of Tianwang Buxin Pills on Behavior, HPA Axis, BDNF Expression and Phosphorylation of GSK3β in Mice with Chronic Unpredictable Stress / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effect of Tianwang Buxin pills on behavior， hypothalamus pituitary adrenal axis （HPA axis）， hippocampal glycogen synthase kinase 3β （GSK3β） phosphorylation and brain-derived neurotrophic factor （BDNF） expression in mice with chronic unpredictable stress， and explore its mechanisms for antidepressant-like action. Method:Totally 60 male ICR mice were randomly divided into normal group， chronic stress model group， fluoxetine hydrochloride group （10 mg·kg-1） and Tianwang Buxin pills high， middle and low dose groups （3.6， 1.8， 0.9 g·kg-1）. The mice were subjected to the chronic unpredictable stress （CUS） protocol for a period of 28 d to induce depressive-like behavior. Then， a sucrose preference test， open-field test and novelty-suppressed feeding test were performed to detect the behavior changes. The blood， adrenal gland and hippocampus of mice were collected. The contents of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The changes of GSK3β phosphorylation and BDNF expression in hippocampus were detected by Western blot， and the adrenal index was then calculated. Result:As compared with the normal group， the sucrose water preference was significantly decreased （P<0.01）， the number of opening activities was significantly reduced （P<0.05）， the feeding latency of novelty inhibition was prolonged （P<0.01）， the serum ACTH and CORT contents were significantly increased （P<0.05，P<0.01）， GSK3β phosphorylation and BDNF expression levels in hippocampus were significantly decreased （P<0.01）， and adrenal index was significantly increased in model group （P<0.01）. As compared with the model group， Tianwang Buxin pills treatment significantly reversed the CUS-induced behavioral abnormalities in depression model mice （P<0.05， P<0.01）， significantly decreased the levels of plasma ACTH and CORT （P<0.01） and adrenal and adrenal gland index （P<0.01）， while increased GSK3β phosphorylation and BDNF expression in hippocampus （P<0.05， P<0.01）， with its effect similar to that of fluoxetine hydrochloride. Conclusion:Tianwang Buxin pills produced antidepressant-like effects in chronic unpredictable stress mice， and its mechanism may be associated with inhibiting HPA axis activity and up-regulating GSK3β phosphorylation and BDNF protein expression in hippocampus.