Plasma components of Danzhi Xiaoyao Formula and its mechanism of action in treating perimenopausal depression based on UPLC-Q-TOF-MS~E integrated with network pharmacology / 中国中药杂志

In this study, ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS~E) was used to analyze the plasma components of Danzhi Xiaoyao Formula after oral administration. Forty-nine plasma components were found in the serum of rats by comparing the compound extract, drug-containing serum, and blank serum. Components, such as 6-hydroxycoumarin, poricoic acid F, deoxoglabrolide, 30-norhederagenin, kanzonol R, 3',6'-di-O-galloylpaeoniflorin, 16α-hydroxytrametenolic acid, 16-deoxyporicoic acid B, 3-O-acetyl-16α-hydroxytrametenolic acid, and 16α,25-dihydroxydehydroeburiconic acid, were first found in rat serum. Behavioral tests, including the tail suspension test, novel object recognition test, and novelty-suppressed feeding test, were conducted for behavioral analysis. It was confirmed that this formula had therapeutic effects on perimenopausal depression. Furthermore, in combination with the network pharmacology method, 53 core targets including MAPK1, HRAS, AKT1, EGFR, and ESR1 were screened, and these targets participated in 165 signaling pathways, including PI3K-AKT, AMPK, VEGFA, MAPK, and HIF-1. In summary, the potential effects of Danzhi Xiaoyao Formula in treating perimenopausal depression are associated with mechanisms in accelerating inflammation repair, improving neuroplasticity, affecting neurotransmitters, regulating estrogen levels, and promoting new blood vessel formation.

Effect and Mechanism of Modified Banxia Xiexintang on Depression During Perimenopause / 中国实验方剂学杂志

Objective::To observe the effect of modified Banxia Xiexintang on depression during perimenopause, in order to study itseffecton 5-hydroxytryptamine (5-HT) and proinflammatory factors. Method::One hundred and thirty-nine patients were randomly divided into control group (69 cases) and observation group (70 cases) by random number table.Patients in control group got tibolone tablets, 2.5 mg/time, 1 time/day, and paroxetine hydrochloride tablets, 20 mg/time, 1 time/day.In addition to the therapy in control group, patients in observation group were added with modified Banxia Xiexintang, 1 dose/day.The course of treatment was 8 weeks.And before and after treatment, Hamilton depression scale for-17 items (HAMD-17), Zung's self-rating depression scale (SDS), hamilton anxiety scale (HAMA), improvement Kupperman(KI), liver depression and spleen deficiency syndrome, menopause-specific quality of life questionnaire (MENQOL) and treatment emergent symptom scale (TESS) were scored, and levels of 5-HT, rain-derived neurotrophic factor (BDNF), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected. Result::After treatment, scores of HAMD-17 and SDS in observation group were lower than those in control group (P<0.01). And the effect on trea depression in observation group was better than that in control group (Z=2.074, P<0.05). The degree of depression in observation group was ligher than that in control group (Z=2.157, P<0.05). And scores of HAMA, KI and liver depression and spleen deficiency syndrome were lower than those in control group (P<0.01). The severity of perimenopausal syndrome was ligher than that in control group (Z=2.046, P<0.05). And scores of vasomotor symptoms and psychological symptoms of MENQOL scale and the total scores were lower than those in control group (P<0.05). Levels of 5-HT and BDNF were higher than those in control group (P<0.01), while levels of IL-1β, TNF-α and TESS were lower than those in control group (P<0.01). Conclusion::In addition to theroutine western medicine, modified Banxia Xiexintang can alleviate the severity of depression, release the symptoms of depression, anxiety and perimenopausal syudrome(PMS), improve the quality of life, inhibit pro-inflammatory factors, and enhance the expressions of 5-HT and BDNF, with no adverse event.

Neuroprotective effects of estrogen on rat model of perimenopausal depression and possible mechanism / 国际药学研究杂志

Objective: To investigate the antidepressant roles of estrogen in the perimenopausal depression rat model and po- tential mechnisms. Methods: The perimenopausal depression rat model was performed by ovariectomized(OVX)rat following unpre- dictable chronic mild stress(UCMS). The rats were divided into 6 groups:the control group(CON),OVX group,model (OVX+UC- MS)group,estrogen(estradiol,E2)treatment group,escitalopram group(ESC),and OVX+E2 group. Open filed and sucrose prefer- ence tests were used to investigate depression-like behavior. Nissl staining was used to analyze neuron numbers in the dentate gyrus (DG)region of rat hippocampus,Levels of 5-HT,5-H1AA, norepinephrine(NE)and dopamine(DA)in the hippocampus were deter- mined by the HPLC method,while the levels of several markers associated with HPA axis were determined by ELISA. Results: OVX+ UCMS decreased the number of crosses and rearings in open field test and decreased sucrose preference in sucrose preference test in the perimenopausal depression rat model. E2 treatment could reverse the depression behavior. E2 treatment also reversed the de- creased neuron numbers of DG region in the rat hippocampus and decreased monamine transmitter and high hypothalamic-pituitary-ad- renal axis(HPA)activation. Conclusion: E2 plays antidepressant roles in perimenopausal depression rat model through protecting neuron,increasing monamine transmitter level and decreasing HPA axis activation.

Changes of spacial learning and memory abilities and ultrastructure of hippocampus in perimenopausal depression model rats / 中华行为医学与脑科学杂志

Objective To observe changes of spacial learning and memory and the ultrastructure of hippocampus in perimenopausal depression model rats. Methods Thirty-six female SD rats were randomly divided into four groups(9 in each). Normal group wasn't given any stress, and stressed group was given isolation-housing in combination with chronic unexpected mild stress (CUMS) for 21 days. Ovariectomized group was given ovary resecting, and model group was made by resecting the ovaries of female rats, then giving isolation-housing in combination with 21 days of CUMS. Morris water maze test were used to test rats' behaviors. Light microscope and transmission electron microscope were used to observe the tissular structure of hippocampus. Results After ovaries resecting and 21 days of CUMS,the escape periods of rats in model group during the first three days ( (44.08 ± 18.29)s; ( 38.80 ± 19.07 ) s; ( 22.74 ± 14.13 ) s) were longer than ovariectomizd group ( (43.68 ± 10. 37 ) s; ( 20.28 ±17.75)s;(21.22 ± 11.91 )s] and normal group( (34.50 ± 11.08)s;(21.42 ± 14.32) s;( 13.94 ±9.76) s). HE staining showed that hippocampal pyramidal cell layer became thinner in rat model of depression,the gap between cells increased,and the cells arrayed in disorder,or loosely,even a large number of cells were lost. Transmission electron microscope showed that in rats of model group, hippocampal neurons were less, nuclear collapsed, the whole nuclear membrane was fuzzy and there were some local fractures in the nuclear membrane. Mitochondria within the cytoplasm were swelling and their ridges disappeared. Conclusion The decline of spacial learning and memory abilities in perimenopausal depression model rats might result from pathological changes in hippocampus.