Si-Wu-Tang Improves Ovarian Function by Regulating Follicular Development Via PI3K/AKT Signaling Pathway in a Mouse Model of Premature Ovarian Failure Induced by Cyclophosphamide

Abstract

Ethnopharmacological relevance: Si-Wu-Tang (SWT) has become a common basic prescription for supplementing blood and regulating menstruation, and enjoys the reputation of “the first prescription in gynecology”. It is often reported in the treatment of premature ovarian failure(POF), menstrual disorders, and dysmenorrhea. However, knowledge of its specific mechanism is still limited.

Aim of the study: This study aimed to investigate the underlying molecular mechanism of pharmacological activity of SWT, via the PI3K/AKT signaling pathway, in the treatment of POF.

Materials and methods: In the current study, we intraperitoneally injected C57/BL6 mice with cyclophosphamide (CTX) to replicate the POF model, and evaluated the effects of SWT on the number of primordial follicles, sex hormone levels, follicular development, angiogenesis of ovarian microenvironment, and the PI3K/AKT signaling pathway.

Results: We found that SWT can inhibit the activity of the PI3K/AKT signaling pathway, alleviate the decrease in the number of primordial follicles induced by CTX, regulate the level of sex hormones, stabilize the estrous cycle, promote the expression of follicular development-related factors BMP-15, GDF-9, BMP-7, AMH, and ovarian microangiogenesis of the environment, and inhibit granular cell apoptosis.

Conclusions: SWT can promote the normal development of follicles and protect ovarian function. These results can provide new ideas for the clinical use of SWT as a primer for the treatment of POF, and provide a theoretical basis for clinicians to use this formula.

Note:
Funding: This work was supported by the National Natural Science Foundation of China (No. 81774090).

Declaration of Interests: The authors declare that there are no conflicts of interest.

Ethics Approval Statement: The animal study was reviewed and approved by the Laboratory Animal Center of Tongji Hospital affiliated with Huazhong University of Science and Technology (ethics approval number: TJH-201901003).

Keywords: Si-wu-Tang，premature ovarian failure，Pi3k/akt signaling pathway，follicular development，angiogenesis