ABSTRACT
OBJECTIVE To study the influence of glycogen synthase kinase3β (GSK3β) over expres?sion in the hippocampus on the antidepressant and anxiolytic effects of total flavoids from Xiaobuxin Tang (XBXT-2). METHODS Adeno-associated virus containing GSK3β(S9A) mutation was microinjected into the hippocampus. After three weeks of recovery, GSK3βand p-GSK3βwere detected by Western blotting, and open field test (OFT) was used to evaluate the locomotor activity. Then, AAV group and GSK3β over expression group were divided into administration group and solvent group, respectively. XBXT-2 (100 mg · kg-1) and solvent were ig administered chronically. After 14 d and 16 d of administra?tion, the tail suspension test (TST) and forced swimming test (FST) were used to investigate the influence of GSK3βover expression on the antidepressant effect of XBXT-2, respectively. After 18 d and 20 d of administration, the elevated plus maze test (EPMT) and staircase test (ST) were used to investigate the influence of GSK3β over expression on the anxiolytic effects of XBXT-2, respectively. RESULTS Western blotting analysis showed that the protein level of GSK3βincreased significantly in GSK3βover expression group (P<0.01) compared with AAV group, but there was no significant difference in p-GSK3β. In OFT, the number of crossings and rearings showed no difference between AAV group and GSK3β over expression group. The results of TST and FST showed that compared with AAV group, the immobility time was significantly reduced in AAV+XBXT-2 group (P<0.05, P<0.01), but compared with GSK3β over expression group, the immobility time showed no difference in GSK3β over expression+XBXT-2 group. In EPMT, compared with AAV group, the percentage of entrances and time into open arms in AAV+XBXT-2 group was significantly increased (P<0.01, P<0.05), but compared with GSK3βover expression group, these indexes showed no difference in GSK3βover expression+XBXT-2 group. In ST, compared with AAV group, the number of rearings was significantly reduced in AAV+XBXT-2 group (P<0.05), but there was no difference between GSK3β over expression+XBXT-2 group and GSK3βover expression group. CONCLUSION GSK3βover expression in the hippocampus can reverse the antidepressant effects of XBXT-2 in the TST and FST, and the anxiolytic effects in the EPM and ST.
ABSTRACT
AIM Xiaobuxin-Tang (XBXT) is a traditional Chinese herbal decoction which is composed of Haematitum, Flos Inulae, Folium Phyllostachydis Henonis and Semen Sojae Preparatum. The present study was to investigate if the total flavonoids extracted from XBXT (XBXT-2) had antidepressant effect. METHODS Forced swimming tests in mice and rats, and learned helplessness (LH) model of rats were adopted to affirm the antidepressant effect of XBXT-2 with the test on spontaneous motor activity. Plasma corticosterone level in the LH rats was measured with ELISA. RESULTS Single administraton of XBXT-2 at the doses of 50 and 100 mg·kg-1 (ig) significantly decreased the duration of immobility time in the forced swimming tests in mice and rats. Researches on LH model of rats indicated that XBXT-2 at doses of 50 and 25 mg·kg-1 markedly reduced the number of escape failure in shuttle box. Meanwhile, the plasma corticosterone level of the LH rats was significantly decreased. XBXT-2 50-200 mg·kg-1 had no effects on spontaneous motor activity in mice. CONCLUSION XBXT-2 possesses significant antidepressant-like effect. The mechanism may involve the inhibition of the hyperaction of the hypothalamic-pituitary-adrenal axis.