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

Clinical complementary medicine and pharmacology Pub Date : 2022-08-27 DOI:10.1016/j.ccmp.2022.100068

Jiawen Ma , Zaiyang Zhang , Xin Yan , Cenglin Xu , Yizhou Zhang

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引用次数: 0

Abstract

Background

The prevalence of premature ovarian insufficiency (POI) is gradually increasing, safer and more effective treatments are urgently needed.

Objective

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.

Methods

Six to eight weeks old female C57BL/6 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/d). 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 was verified through western blotting experiments finally.

Results

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 (E₂), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Moreover, some crucial key gene targets including TP53 were as propose to be relate 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 ovaries.

Conclusion

Our findings proposed that NXYSF might be an effective alternative treatment for POI.

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宁心益肾方通过抑制p53对d -半乳糖诱导的小鼠卵巢早衰的影响

背景卵巢功能不全(POI)的发病率正在逐渐上升，迫切需要更安全、更有效的治疗方法。目的观察宁心益肾方对d -半乳糖诱导的POI小鼠的影响，并探讨其作用机制。方法选用6 ~ 8周龄雌性C57BL/6小鼠，随机分为6组:对照组;模型组;戊酸雌二醇(EV)治疗组和NXYSF治疗组按剂量分级(9.5、19和38 g·kg−1/d)。EV和NXYSF均于造模第15天开始处理，持续28 d。然后，通过分析各组原始卵泡比例和血清性激素水平来评估卵巢功能。此外，采用网络药理学方法阐明NXYSF的潜在靶点，最后通过western blotting实验进行验证。结果snxysf能明显扭转POI引起的增重效率低下，促进原始卵泡发育。此外，它还能恢复异常的血清抗勒氏激素(AMH)、雌二醇(E2)、促黄体生成素(LH)和促卵泡激素(FSH)。此外，通过网络药理学分析，提出了包括TP53在内的一些关键基因靶点与NXYSF的作用有关。最后，western blotting实验证实NXYSF可以抑制小鼠卵巢中p53蛋白的表达。结论NXYSF可能是治疗POI的有效替代方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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