Total flavonoids extracted from xiaobuxin-tang on hyperactivity of hypothalamic-pituitary-adrenal axis in mouse learned helplessness model / 中国药理学通报

ABSTRACT

Aim To investigate the effect of the total flaconoids extracted from Xiaobuxin-Tan g ( XBXT-2 ) on the hyperactivity of hypothalamic-pituitary-adrenal axis in mouse learned helplessness model. Methods Learned helplessness was induced by inescapable foot shock stress over 1h session for 5 days. After screen-ing, we divided learned helplessness mice into five groupsIS, inescapable shock;Dlx, dulxetine(20 mg ·kg-1);XBXT-2(25,50 mg·kg-1). Latency to es-cape shocks and escape failure had been recorded. During the test, Dlx(20 mg·kg-1 ) and XBXT-2(25, 50 mg·kg-1 ) were administered intragastrically once daily for four days. Serum corticosterone level and ad-renocorticotropic hormone ( ACTH ) level were meas-ured by ELISA, and expression of glucocorticoids re-ceptor ( GR) α/β and brain-derived neurotrophic fac-tor ( BDNF ) in hippocampus was determined using Western blot method. Results XBXT-2 (25,50 mg· kg-1 ) or duloxetine treatment showed antidepressant effect in mouse learned helplessness model, as demon-strated by the decreased escape failure and escape la-tency. Our ELISA results showed that XBXT-2 or du-loxetine significantly decreased serum corticosterone level and its upstream stress hormone ACTH level in learned helplessness mice. Furthermore, Western blot result demonstrated XBXT-2 treatment increased GRs and BDNF expression in hippocampus. Conclusions XBXT-2 produces significant antidepressant effect on learned helplessness mice. In addition, the modulation of HPA axis produced by XBXT-2 may be important mechanism underlying its antidepressant-like effect in mouse learned helplessness model.