Objective To explore the efficacy and potential mechanism of Jiawei Baihe Dihuang Decoction(JWBHDHD)in treating perimenopausal depression based on the hypothalamic-pituitary-ovarian axis(HPO axis)and estrogen receptor(ER).Methods The rats were randomized into normal control group,model group,positive drug group(1.89 mg/kg of flupentixol-melitracen solution),and high-,medium-,and low-JWBHDHD doses(16.2,8.1,4.05 g/kg)groups,with 10 rats in each group.Except the normal control group,all the other groups were established a perimenopausal depression rat model by bilateral ovariectomization combined with chronic unpredictable stress.After 21 days of administration in each group,a sugar preference test and a forced swimming test were used to evaluate the depression-like behavior of rats;enzyme-linked immunosorbent assay was used to check serum gonadotropin-releasing hormone(GnRH),follicle-stimulating hormone(FSH),luteinizing hormone(LH),and estradiol(E2)levels;HE staining was used to observe the histopathological damage of the hypothalamus,pituitary gland,and hippocampus;the expressions of estrogen receptor genes and proteins in the hypothalamus and hippocampus tissues were detected by RT-PCR and Western blot.Results Compared with the normal group,the preference for sugar water of rats in the model group significantly decreased(P<0.01),the immobility time of forced swimming significantly increased(P<0.01),and the rats in the model group showed obvious depression-like behaviors,the content of serum GnRH,FSH,and LH was significantly higher(P<0.01 or P<0.05),and E2 was lower(P<0.01).The hypothalamus,pituitary,and hippocampal tissues were damaged,and the expression of estrogen receptors was significantly lower(P<0.01).After the intervention of JWBHDHD,the depression-like behavior of model rats was significantly improved(P<0.01 or P<0.05),the hyperactivity of HPO axis and hippocampal injury were relieved,and the expression of estrogen receptor in hypothalamus and hippocampal significantly increased(P<0.01 or P<0.05).Compared with the positive drug group,the expression of estrogen receptor genes in the hypothalamus of the high-dose JWBHDHD group significantly increased(P<0.05).Conclusion JWBHDHD exerts an anti-perimenopausal depression role by inhibiting HPO axis hyperactivity and increasing estrogen receptor levels in the brain.
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