ABSTRACT
Objective:To explore the effective components， targets， and possible mechanisms of Wenshen Yangxue prescription in improving endometrial receptivity of aged female mice based on network pharmacology and experimental verification. Method:Based on Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine， the components and targets of Wenshen Yangxue prescription were retrieved， and the targets of ovulatory dysfunctional infertility were collected from the Online Mendelian Inheritance in Man （OMIM） and GeneCards with "anovulatory sterility" and "anovulatory infertility" as keywords. The protein-protein interaction （PPI） network was constructed based on STRING and the core targets of Wenshen Yangxue prescription against ovulatory dysfunctional infertility were screened by Cytoscape， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of the core targets in DAVID database. Then， the "medicinal-component-target-pathway" network was established and the core targets were verified by animal experiment. Result:A total of 253 components and 326 targets of Wenshen Yangxue prescription， 819 disease targets， and 74 common targets were screened out. The common targets were mainly involved in the biological processes such as positive regulation of nitric oxide biosynthetic process， positive regulation of cell proliferation， response to estradiol， aging， response to oxidative stress， and angiogenesis. The GO term of response to oxidative stress and five of the top 20 KEGG pathways were analyzed. According to the "medicinal-component-target-biological process/pathway" network， 41 chemical components in 20 medicinals participated in hypoxia inducible factor-1 （HIF-1） signaling pathway， tumor necrosis factor （TNF） signaling pathway， forkhead box O （FOXO） signaling pathway， Toll-like receptor （TLR） signal pathway， and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway by affecting 35 targets. The results of animal experiment showed that the prescription could increase the expression of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， forkhead box O3A （FoxO3A）， and phosphorylated FoxO3A （p-FoxO3A） in uterus of aged female ICR mice. Conclusion:Wenshen Yangxue prescription interferes with oxidative stress and PI3K/Akt/FoxO3A signaling pathway by influencing Akt1， dual oxidase 2 （DUOX2）， epidermal growth factor receptor （EGFR）， heme oxygenase-1 （HMOX1）， myeloperoxidase （MPO）， and other targets， thereby improving endometrial receptivity of aged female mice.
ABSTRACT
Objective:To observe the effect of Zikun decoction (ZKD) in treatment of Yin deficiency and blood dryness in delayed menorrhea due to decreasing ovarian reservation．Method:A total of 60 cases were randomly divided into two groups．The observation group was given ZKD orally，and the control group was treated with complex packing estradiol tablets/estradiol and dydrogestero for three months．The control group began to take medicine on the first day of menstruation for 28 days, while the observation group began to take medicine on the fifth day of menstruation, and stopped taking medicine on the first day of the next menstruation. Three menstrual cycles were followed up. The clinical syndrome scores, follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B (INHB), FSH/LH, Estradiol (E2), anti-müllerian hormone (AMH), and antral follicle count (AFC) scores of the patients before and after treatment were compared.Result:After treatment, there was no significant difference in clinical efficiency between observation group and control group, but the traditional Chinese medicine syndrome score of observation group was significantly reduced (P<0.05), observation group and control group had the same curative effect in improvement of FSH, FSH/LH, AMH and AFC (P<0.05), but ZKD was better than complex packing estradiol tablets/estradiol and dydrogestero in improvement of INHB.Conclusion:ZKD has a good treatment effect in the treatment of DOR. It can effectively improve patients' sex hormone levels, increase antral follicle count, improve the ovarian reserve function and promote menstruation.