Effect of Ningxin-Yishen Formula on D-galactose-induced Premature Ovarian Insufficiency Mice by Inhibiting p53

Abstract

: The prevalence of premature ovarian insufficiency (POI) is gradually increasing, safer and more effective treatments are urgently needed. The aim of this study was to evaluate the effects of Ningxin-Yishen formula (NXYSF) on D -galactose-induced POI mice as well as to shed a light on its potential mechanisms. : Six to eight weeks old C57BL/6 female mice were used in this study and randomly divided into six groups: control group; model group; estradiol valerate (EV) treatment group and NXYSF treatment group with graded doses (9.5, 19, and 38 g∙kg −1 /day). Both EV and NXYSF treatments were initiated at the 15th day of modeling and lasted for 28 days. Afterwards, the ovarian function was evaluated in each group by analyzing the proportion of primordial follicles as well as the serum sex hormone levels. Furthermore, network pharmacology approach was performed to elucidate the potential targets of NXYSF, which were verified through western blotting experiments finally. : NXYSF could significantly reverse the inefficiency of weight gain caused by POI, and promote the development of primordial follicles. In addition, it could restore the abnormal serum anti-Müllerian hormone (AMH), estradiol (E 2 ), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Moreover, some crucial key gene targets including TP53 were proposed to be related with the effect of NXYSF through network pharmacology analysis. Last but importantly, western blotting experiments confirmed that NXYSF could inhibit the expression of p53 protein in mouse ovary. : Our findings proposed that NXYSF might be an effective alternative treatment for POI.