The Anti-depression Effect And Possible Mechanisms Of Orcinol Glucoside On The Perimenopausal Depressive Mice Model

Context: Orcinol Glucoside(OG),a Phenol glucoside isolated from Curculigo orchioides,showed the antidepressant-like effect on chronic unpredictable mild stress(CUMS)-induced rats previously.Objectives:This study was designed to determine whether OG could improve the depressive-like symptoms of perimenopausal depression(PMD)and the possible mechanisms involved.Methods: This research was performed on a perimenopausal depression(PMD)mice model established by a two-steps method of ovariectomy(OVX)followed CUMS.In order to detect the effect of OG on perimenopausal depressive mice model,we observed the body weight changes weekly and tested the changes of depressive behaviors on mice in SPT,OFT,FST and TST.The business Elisa kit were used to measuring the hormone levels related to the HPA/HPO axis.The m RNA expression levels of CRH,CRH-R1,FSH,FSH-R were tested by q RT-PCR.The related protein expressions of BDNF-Trk B signaling pathway were quantified by Western Blot.Results: OG treatment effectively improved the depressive-like behaviors of OVX-CUMS mice,as indicated by increased sucrose intake in sucrose preference test(SPT),reduced immobility time in forced swimming test(FST)and tail suspending test(TST),lower frequency of grooming and defecation,increased actions of rearing and prolonged duration in the center in open field test(OFT).OG treatment alleviated the OVX-CUMS induced dysfunction of hypothalamic-pituitray-ovarian(HPO)axis by increased serum estradiol(E2)and decreased ovarian hormones FSH,LH and Gn RH in serum.Meanwhile,OG reversed the hyperactivity of hypothalamic-pituitary-adrenal(HPA)axis as evidenced by decreased CORT and ACTH in serum,reduced as well as the m RNA and protein expression of CRH in hypothalamus and hippocampus.Moreover,OG up-regulated the protein expression of BDNF,Trk B and phosphorylation level of CREB and ERK1/2 in hippocampus.Conclusions: These findings demonstrated that OG improves depressive behaviors of OVX-CUMS mice by modulating of HPO/HPA axis dysfunction,and activating BDNF-Trk B-CREB signaling pathway.