Study on mechanism of Bushen Culuan Formula in treatment of polycystic ovary syndrome based on network pharmacology and molecular docking / 中国中药杂志

This study used network pharmacology and molecular docking to study the mechanism of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS). The active ingredients and potential drug targets of Bushen Cu-luan Decoction were obtained by searching the Traditional Chinese Medicine System Pharmacology(TCMSP) database, and the targets of PCOS by searching GeneCards. After the drug targets and disease targets were corrected by Uniprot, the intersection genes were obtained. STRING database and Cytoscape 3.7.2 were used for protein-protein interaction(PPI) analysis of the intersection genes. The ClueGO plug-in of Cytoscape 3.7.2 was employed to perform gene ontology(GO) enrichment and KEGG pathway enrichment for the intersection genes. Finally, molecular docking of the key active ingredients with the targets of Bushen Culuan Formula was performed using AutoDockVina and MGLtools. A total of 136 active ingredients and 314 drug targets of the decoction were obtained from TCMSP, and 136 disease targets from GeneCards. Finally, 49 drug-disease intersection genes were obtained. GO enrichment found that the genes were mainly involved in the regulation of muscle cell apoptosis, positive regulation of small molecule metabolism, core promoter binding, RNA polymerase Ⅱ regulation of pri-miRNA transcription, negative regulation of transmembrane transport and other biological functions. The enriched KEGG pathways mainly included MAPK, PI3 K-Akt, p53, and HIF-1 signaling pathways. The results of molecular docking showed that quercetin and PTGS2 can bind stably and interact through amino acid residues THR206, TRP387, ASN382, etc. This study preliminarily reveals the multi-component, multi-target, and multi-pathway mechanism of Bushen Culuan Formula in the treatment of PCOS-related infertility, which provides a basis for further research.

Effect of therapies for kidney-tonifying and blood-activating in treatment of anovulatory infertility in eugenics / 中国中药杂志

In the context of the new era, paying attention to maternal and child health and advocating prenatal and postnatal care can effectively improve the quality of the birth population. Traditional Chinese medicine has a long history of prenatal and postnatal healthcare with rich content, which is the theoretical basis of modern related services. With the social development and the improvement of people's awareness of prenatal and postnatal healthcare, people have gradually shifted the focus of prenatal and postnatal healthcare to the peri-pregnancy stage at present, namely that couples of childbearing age are guided to prepare for pregnancy under the premise of solving their basic diseases. Infertility is a common and refractory disease for women of childbearing age. Ovulation disorder is one of its common pathological mechanisms. Traditional Chinese medicine believes that kidney deficiency is the main cause and pa-thogenesis of anovulation infertility and blood stasis is an important factor throughout the disease course. In clinical practice, therapies for invigorating kidney and activating blood are safe and reliable to treat anovulatory infertility mainly by adjusting the hypothalamus-pituitary-ovarian axis, improving ovarian function, uterine environment and gamete quality and increasing endometrial volume. Under the guidance of the thought of prenatal and postnatal healthcare, the authors tried to explore the effect of therapies for kidney-tonifying and blood-activating in the treatment of anovulatory infertility in eugenics, with the purpose of providing ideas and basis for subsequent relevant clinical studies and contributing to prenatal and postnatal healthcare services.

Effect of Dingkundan on Sex Hormone and Follicle Count in Mice of Tripterygium Wilfordii Polyglycosides Induced Diminished Ovarian Reserve / 中国实验方剂学杂志

Objective:To establish a mouse model of diminished ovarian reserve （DOR） induced by tripterygium wilfordii polyglycosides （TWP）， and to explore the therapeutic effect of Dingkundan （DKD） on DOR， so as to provide scientific basis for its clinical application. Method:The 60 female Blab/c mice with regular estrous cycle were randomly divided into blank group， model group， low，medium and high-dose DKD group， DKD group and estradiol valerate group， with 10 mice in each group. Except the blank group， the other groups were given 40 mg·kg-1 TWP suspension. Meantime，low，medium and high-dose DKD group were given 1.64，3.28，6.56 g·kg-1 DKD suspension respectively， and estradiol valerate group was given 0.15 mg·kg-1 estradiol valerate suspension by gastric lavage once a day for 30 days. The general condition， body weight， estrous cycle and gonad index of mice were observed， serum follicle-stimulating hormone （FSH）， luteinizing hormone （LH） and estradiol （E2） were determined by radioimmunoassay， ovarian morphology and follicle count were observed by hematoxylin-eosin staining （HE） staining. Result:Compared with the blank group， most of the mice in model group had disordered estrous cycle， uterine and ovarian indexes decreased （P<0.05）， serum FSH increased （P<0.05）， LH was on an upward trajectory， E2 was on a downward trend， and the number of growth follicles and corpus luteum decreased and the number of atresia follicles increased（P<0.05）. Compared with the model group， half of the mice in DKD group resumed regular estrous cycle， however， the estrous cycles of mice in estradiol valerate group were stagnated during estrous period. In medium-dose， high-dose DKD group and estradiol valerate group， the uterine and ovarian indexes of the mice were increased， the serum FSH value decreased （P<0.05） and serum LH was on a downward trend， high-dose DKD group and estradiol valerate group increased the levels of serum E2 （P<0.05）. In DKD group， the number of growth follicles and corpus luteum were increased and the number of atresia follicles were reduced （P<0.05）， with the best effect at medium dosage. And in estradiol valerate group， the number of primitive follicles， sinusoidal follicles and corpus luteum were increased （P<0.05）， but the number of atresia follicles had no difference to the model group. Conclusion:DKD can improve serum sex hormones， promote follicular development and reduce follicular atresia， which can play a therapeutic role in the treatment of DOR.

Establishment of premature ovarian insufficiency kidney deficiency and blood stasis pattern mouse model with Tripterygium wilfordii polyglycoside for Bushen Culuan Decoction therapy / 中国中药杂志

To establish a mouse model of premature ovarian insufficiency( POI) with kidney deficiency and blood stasis pattern by Tripterygium wilfordii polyglycoside( TWP) gavage,and to evaluate the ovarian function and fertility of the model,in order to find Bushen Culuan Decoction therapeutic mechanism. 60 SPF level Blab/c female mice with normal estrous cycle were randomly divided into 6 groups of 10 each: blank group 1( BG1),blank group 2( BG2),blank fertility group( BFG),model group( MG),model recovery group( MRG) and model fertility group( MFG). The mice in three model groups were treated by gastric gavage with TWP suspension 40 mg·kg-1 twice a day for 14 days,while the mice in three blank groups were treated by gastric gavage with same volume normal saline for 14 days. The mice in BG1 and MG were sacrificed and dissected on day 15. The mice in BG2,BFG,MRG and MFG were returned normal feeding from day 15 and were sacrificed and dissected on day 29. The mice in BFG and MFG were cohabited with male mice with a ratio of 2 ∶1( female ∶male) from day 15. The general situation and estrous cycles of all mice were observed every day. Serum sex hormone levels,ovarian index,uterine index,ovarian morphology,follicle count,ovarian VEGF and ES index were observed within the mice in BG1,BG2,MG and MRG. Pregnancy rate,litter size,survival number of newborn mice and male-female proportion were reported within the mice in BFG and MFG. In model establishing stage,the body weight of mice significantly decreased( P <0. 05) in MG and MFG. Compared with BG1,the mice in model group had irregular estrous cycle,decreased ovarian and uterine indexes,less primordial and developing follicles,more atretic follicles,increased VEGF expression and decreased ES expression( P <0. 05). Compared with blank group 2,the mice in model recovery group had irregular estrous cycle,increased FSH level,decreased ovarian indexes,less primordial and developing follicles,more atretic follicles,increased VEGF expression( P<0. 05). Compared with blank fertility group,the mice in model fertility group had smaller litter size and newborn mice survival count( P<0. 05). Gastric gavage with TWP 40 mg·kg-1 twice a day for 14 days is a feasible way to establish a POI kidney deficiency and blood stasis pattern mouse model. The mice ovarian functions didn't recovery on day 14 after stopping TWP intervening,which could suggest the effectiveness of subsequent therapeutic intervention.