Radix Bupleuri Chinensis Extract Ameliorates Doxorubicin-Induced Spermatogenic Dysfunction: Involvement of the GnRHR...

Background: Male infertility, largely driven by declining sperm quality, is a growing global concern. Radix Bupleuri Chinensis (Chaihu, CH)-a key component of traditional formulas such as Chaihu Shengjing Tang and Chaihu Shugan San-has been clinically used to enhance sperm quality. However, the specific role and mechanism of CH as a single entity in ameliorating spermatogenic dysfunction remain unclear. This study aimed to determine whether CH extract ameliorates spermatogenic dysfunction and whether GnRH/GnRHR signaling and taurine biosynthesis are involved. Methods: Male Kunming (KM) mice and GC-1 spermatogonial cells were used to establish experimental models. Histopathological and cellular changes were examined via hematoxylin and eosin (H&E) staining and immunofluorescence. Enzyme and hormone levels were quantified, while gene and protein expression were analyzed using quantitative real-time polymerase chain reaction, Western blotting, and high-content imaging. Results: CH extract mitigated DOX-induced spermatogenic dysfunction by activating the GnRHR signaling pathway, enhancing taurine biosynthesis, and reducing oxidative stress. In vitro, saikosaponin D alleviated DOX-induced injury in GC-1 cells and was associated with changes in GnRHR-related signaling and taurine-biosynthesis-related proteins, supporting its potential role as a candidate bioactive constituent of CH. Conclusions: CH extract alleviated DOX-induced spermatogenic impairment in mice. The in vivo cetrorelix experiments support the involvement of the GnRHR signaling pathway, whereas the concurrent changes in taurine, CDO1, and FMO1 are consistent with enhanced taurine biosynthesis. These findings provide experimental support for further investigation of CH as a potential intervention for chemotherapy-related reproductive injury.