Effect of Si Jun Zi tang on premature ovarian failure through regulation of ROCK1/PTEN/PI3K/Akt pathway

The main cause of decreased or absent female fertility is a complex, heterogeneous condition known as premature ovarian failure (POF). Surprisingly, POF can be effectively treated using traditional Chinese medicine. Si Jun Zi Tang (SJZT) has unique approaches for treating POF, although they have not been thoroughly investigated. This study aims to explore the impact of SJZT on ovarian function.

The POF mouse model was induced using the Cyclophosphamide (CTX) method. Throughout the therapy, the mice's body weight was monitored, and ovarian tissue pathology was observed using HE staining. Serum levels of FSH, E2, and LH were quantified using the ELISA method. qRT-PCR was employed to measure ROCK1 and PTEN mRNA levels in the ovaries. Protein expressions of PTEN, PI3K, p-PI3K, Akt, p-Akt, and apoptosis-related proteins Cleaved Caspase3, Caspase3, Bax, and Bcl-2 were assessed via Western blot analysis. Additionally, the TUNEL assay was utilized to quantify apoptotic cells in the ovaries.

In a dose-dependent manner, SJZT therapy reversed the CTX-induced decrease in developing follicles and the increase in atretic follicles, maintaining relatively normal blood levels of LH, FSH, and E2. By modulating the mRNA expression of ROCK1 and PTEN, SJZT treatment was associated with reduced activation of PI3K/Akt signaling and mitigated ovarian dysfunction. Additionally, SJZT effectively decreased apoptosis in the ovarian tissues of mice serving as models for POF.

These findings suggest that SJZT may protect ovaries from CTX-induced damage, potentially through modulation of the ROCK1/PTEN/PI3K/Akt pathway, providing insights into possible mechanisms of damage and CTX-induced cellular apoptosis. The study indicates a potential role of SJZT in the treatment of POF.