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Studies have shown that women's menopause caused by permanent cessation of ovarian function is closely related to lipid metabolism disorders. Er-xian Decoction has been used in the clinical treatment for gynecological diseases and has a good effect on diseases related to reduced sex hormone function. In this study, metabolomics was performed on bilateral ovariectomized model rats within 12 weeks after modeling to mimic the physiological state of menopausal women in different menopausal stages and Er-xian Decoction dosed model rats. The results of liver oil red O staining sections showed lipid metabolic disorder of bilateral ovariectomized model rats and the regulating effects of Er-xian Decoction. 46 potential biomarkers (6 steroid hormones, 3 sphingolipids, 11 phospholipids and 26 glycerides) in plasma and 32 potential biomarkers (1 steroid hormones, 20 phospholipids and 11 glycerides) in liver were obtained based on lipidomics analysis. Then, we analyzed the differential metabolic pathways and construct the lipid metabolism network significantly regulated by Er-xian Decoction. The results provided valuable information for in-depth understanding of the gradual changes on lipid metabolism disorders under menopausal conditions and the characteristics and mechanisms of compound Er-xian Decoction's regulatory effects. The study complied with the procedures established by the Animal Experiment Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and passed the animal experiment ethics examine (No. 00000918).
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Objective To explore the effect of antiosteoporotic active fraction from Er-Xian Decoction (EXD) on retinoic acid-induced osteoporosis in rats. Methods Sixty female SD rats were randomly divided into normal control group, model group, estradiol valerate (0.2 mg/kg) group and antiosteoporotic active fraction from EXD low-, middle- and high-dose groups (50, 100, 200 mg/kg). Except for the rats of normal group, the others were intragastrically treated with 70 mg/(kg • d) of retinoic acid for 14 days to induce osteoporosis. Then the rats were treated with estradiol valeratse or antiosteoporotic active fraction from EXD (10 mL/kg) for 28 days. The biochemical parameters in serum and urine of rats were detected by ELISA. The bone mineral density and trabecular bone microstructure of distal femur were analyzed with micro-CT. Results The antiosteoporotic active fraction from EXD significantly decreased calcium content in urine and activities of alkaline phosphatase and tartratse-resistant acid phosphatase in the sera of retinoic acid-induced osteoporotic rats (P0.05, P0.01). High-dose of antiosteoporotic active fraction from EXD significantly increased bone mineral density of distal femur (P0.05). And the antiosteoporotic active fraction from EXD improved the trabecular bone microstructure of distal femur in retinoic acid-induced osteoporotic rats. Conclusion Antiosteoporotic active fraction from EXD can reduce bone loss and deterioration of bone microstructure in retinoic acid-induced osteoporotic rats.
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To investigate the effect of Er-xian decoction on ovariectomy induced-learning and memory disability in rats based on the differences in hippocampus proteomic expression, the female rats were ovariectomized for perimenopausal status and then randomly divided into 3 groups, namely sham group, control group and Er-xian decoction group. The rats in sham group and control group were given normal saline by gavage everyday, the rats in Er-xian decoction group were given 12 g·kg⁻¹ of Er-xian decoction by gavage once a day. After treatment for 90 day, all of the animals were tested by Morris water maze, and all of the samples were collected for testing. The hippocampus proteins were detected by Nano-LC-LTQ-Orbitrap system, and identified by Protein Discovery software. The intensity of differential proteins were quantitated by SIEVE software，and the biological functions of protein were analyzed by DIVAD database. The results showed that Er-xian decoction could significantly improve the abilities of learning and memory. Compared with control group， 216 differential proteins with a consistent variation trend with the sham group were found in the Er-xian decoction group. And they mainly concentrated in calcium signaling pathway, Rab3A and Rab14 were key genes with the highest functional classification enrichment score in the gene group. Er-xian decoction could significantly improve the abilities of learning and memory in perimenopausal model rats. The invention effect of Er-xian decoction may be correlated with the calcium signaling pathway and Ras-related protein Rab-3A, and Ras-related protein Rab-14.
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This experiment was mainly aimed to investigate the effect of Er-xian decoction on osteoporosis and the femur proteomics in ovariectomized rats with osteoporosis. The female SD rats were randomly divided into sham operation group, model group, Alendronate group (1 mg•kg⁻¹), Er-xian decoction group (in dose of 8 g•kg⁻¹) according to their weight. The rats in sham operation group and model group were gavaged with normal saline; the rats in Alendronate group were gavaged with the Alendronate at the dose of 1 mg•kg⁻¹ and the rats in Er-xian decoction group were gavaged with Er-xian decoction at the dose of 8 g•kg⁻¹, once a day for continuous 90 days. Then the femoral bone mineral density (BMD) was detected. The femoral bone proteins were detected by NanoLC-LTQ-Orbitrap system, identified by Protein Discovery software, and the intensity of differentially expressed proteins were quantitated by SIEVE software. The results showed that Er-xian decoction could significantly improve femoral BMD in ovariectomized rats. As compared with model group, 41 differentially expressed proteins whose variation trend was consistent with the sham operation group, were found in Er-xian decoction group, mainly including biological oxidation related protein, signal transduction pathway related protein, proteins involved in aliphatic acid metabolism, cytoskeleton related protein, proteins involved in energy metabolism, and proteins involved in glucose metabolism etc. The osteoporosis could be prevented and cured by Er-xian decoction. The differentially expressed proteins such as carbonic anhydrase 2 and integrin β1 may be the action targets for Er-xian decoction.
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Objective To observe the effect of cupping plus medication on the quality of life and estrogen level in perimenopausal syndrome patients. Method A total of 40 eligible perimenopausal syndrome patients were randomized into a cupping-medication group and a Chinese medication group, 20 cases in each group. The Chinese medication group was intervened by Er Xian decoction, the cupping-medication group was intervened by moving cupping on the back in addition to the treatment given to the Chinese medication group, once a week. Each item of the Menopause-specific Quality of Life (MENQOL), the levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteotropic hormone (LH) in serum were observed before and after the treatment, and the results were analyzed. Result After two treatment courses, the vasomotor symptoms, mental state, physiological state, and sexual life scores in the two groups were significantly improved compared to the scores before the treatment (P0.05). Conclusion Moving cupping on the back plus Er Xian decoction can effectively improve the quality of life of perimenopausal syndrome patients and significantly increase the serum E2 level, superior to using Er Xian decoction alone.
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This study was aimed to investigate effects of Er-Xian (EX) decoction in follicular granulosa cell apoptosis in chemotherapy-induced premature ovarian failure (POF) of rats. SD rats were randomly divided into the normal group, model group, positive group and EX decoction group. Intraperitoneal injection of cisplatin was used in the establishment of chemotherapy-induced POF rat model. Intragastric administration of corresponding medication was give to each group for four weeks. The general conditions of rats were observed. The serum contents of E2, FSH, LH and Pro were determined. The ovarian tissue morphology was observed. Granulosa cell apoptosis was analyzed by TUNEL. The expressions of BAX, Bcl-2 and VEGF protein were detected by immunohistochemistry. The results showed that in the model group, the body weight decreased with disordered estrous cycle. After treatment, the weight gained, and the estrous cycle recovered. Compared with the normal group, in the model group, E2 decreased, FSH and LH levels increased. There was no significant difference in the content of progesterone among different groups. Detection of TUNEL showed that the positive expression in the model group was increased compared with the normal group (P < 0.05). The positive expression of EX decoction group was reduced compared to the positive group (P < 0.05). Compared with the normal group, the expression of BAX was obviously increased and Bcl-2 was decreased in the model group. After EX decoction treatment, the expression of BAX was decreased and the Bcl-2 was increased compared to the model group. The expression of VEGF protein in the model group was obviously less than that in the normal group. It was concluded that cisplatin can induce follicular granulosa cell apoptosis, and cause premature ovarian function recession. EX decoction can adjust the content of different hormones in serum, alter expression of apoptosis related protein to reduce the damage of cisplatin on ovarian follicular development, in order to promote follicular development, improve and enhance the ovarian function.
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Objective: To investigate the protective effects of Er-xian decoction on ovariectomy-induced osteoporosis in rats. Methods: The osteoporosis model was induced by ovariectomy in rats. Twelve weeks later, the undecalcified longitudinal proximal tibial metaphysical sections were made and stained for the bone histomorphometric analysis. Bone density of femur metaphysis was determined by dual-energy X-ray absorptiometry. Results: Er-xian decoction significantly increased trabecular area and trabecular thickness (P<0.01) and decreased trabecular separation (P<0.05). The parameters of bone formation of rats, such as MAR, BFR /BS, BFR/BV, and BFR/TV, were increased significantly after Er-xian decoction treatment (P< 0.05, P<0.01). Moreover, Er-xian decoction obviously reduced osteoclast number (P<0.01) and enhanced bone density of femur metaphysis in ovariectomized rats (P < 0.05). Conclusion: Er-xian decoction has antiosteoporotic effects on ovariectomized rats by promoting bone formation, increasing bone density, and inhibiting bone resorption.
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Objective To explore the possible functional mechanism of Er-xian Decoction and its component herbs on the expression of extrogen receptor(ER) in adrenal development rats.Methods Fifty-four development female SD rats were randomly divided into nine groups:normal control group(A),positive control group(B),Er-xian Decoction group(C),Herba Epimedii group(D),Rhizoma Curculiginis group(E),Radix Morindae Officinalis group(F),Radix Angelicae Sinensis group(G),Cortex Phellodendri group(H),Rhizoma Anemarrhenae group(I).After the rats were administrated for six days,serum were got to measure testosterone(T).Bilateral adrenal gland was weighed and embedded by paraffin.Mean optical density(MOD) were studied by the immunohistochemical method and image analyzing system.Results The adrenal coefficient was increased in group B and C,and the level of T was decreased in group C,D,E and I.ER? was mainly observed in the cytoplasm of zona glomerulosa and zona fasciculate.MOD in group C was increased while declined in group B.ER? was mainly observed in nucleus of zona glomerulosa and zona fasciculate.MOD in group C,D,E and I was less than group B.Conclusion Er-xian Decoction and its component herbs of warming Shen(Herba Epimedii,Rhizoma Curculiginis) and nourishing Yin(Rhizoma Anemarrhenae) play a phytoestrogen role by influencing the expression of ER? and ER ? in the adrenal cortex.