The Guangsi Yulin Decoction Inhibits Oxidative Stress and Inflammation-Induced Spermatogenesis Dysfunction via the PTEN/ PI3K/ AKT/ FoxO1 Pathway

Guangsi Yulin Decoction (GSYLD) is a traditional Chinese medicine (TCM) formula with therapeutic efficacy against spermatogenesis dysfunction. However, the underlying mechanism of the alleviation remains unclear. To investigate the effects of GSYLD on Tripterygium wilfordii polyglycolide (GTW)-induced spermatogenesis dysfunction in mice and to explore associated mechanisms, particularly its role in oxidative stress and inflammation. A total of 60 (7-8-week-old) BALB/c mice were grouped into control (NC), model (GTW), low-dose GSYLD (GSYLD-L, 0.27 g/kg/d), high-dose GSYLD (GSYLD-H, 1.08 g/kg/d), and PTEN inhibitor (1.08 g/kg/d GSYLD-H + 0.3 mg/kg PTEN inhibitor). After eight weeks, the model was validated, and semen quality was evaluated by assessing sperm vitality and concentration. Testicular tissues were analyzed by H&E staining, while Western blotting and RT-qPCR (Reverse Transcription Quantitative PCR) were used to assess the therapeutic efficacy of the GSYLD. In comparison to the GTW group, the GSYLD-H group showed a significant improvement in sperm vitality and concentration (p < .01). GSYLD upregulated PI3K, Akt, and FOXO1, while downregulating PTEN mRNA expression (p < .001). A parallel recovery was observed at the protein level. Specifically, the GSYLD-H group exhibited a significant amelioration of oxidative stress and inflammation, marked by reduced MDA, TNF-α, and IL-6 levels (p < .01) and enhanced SOD activity (p < .001) relative to the GTW group. GSYLD alleviated GTW-induced spermatogenesis dysfunction, potentially through PTEN/PI3K/Akt/FOXO1-mediated regulation of oxidative stress and inflammation.

PTEN/PI3K/AKT/FoxO1 signaling pathway; Tripterygium wilfordii polyglycolide; spermatogenesis dysfunction; traditional Chinese medicine.