Shenling Baizhu San attenuates testicular spermatogenic dysfunction in hyperuricemic mice via dual modulation of MAPK/NF-κB and NLRP3 inflammasome pathways.

Context: Hyperuricemia (HUA) is a known factor contributing to testicular spermatogenic dysfunction. Shenling Baizhu San (SLBZS), a traditional Chinese medicine compound, has demonstrated efficacy in reducing uric acid levels. However, its specific impact on testicular spermatogenic function in mice with HUA remains unclear.

Objective: To investigate the impact and mechanism of SLBZS on testicular spermatogenic function in HUA mice.

Materials and methods: A hyperuricemia-induced spermatogenic dysfunction model was created by administering intraperitoneal injections of potassium oxonate (600 mg/kg/d) for seven days. Following model establishment, 48 Balb/c mice were randomly divided into six groups: control, model, low-dose SLBZS (5.04 g/kg/d), medium-dose SLBZS (10.07 g/kg/d), high-dose SLBZS (20.14 g/kg/d), and febuxostat (10 mg/kg/d). All groups, except the control, underwent model induction, followed by specific interventions. Subsequent analyses included serum uric acid levels, testicular and epididymal indices, histopathological assessments, sperm quality, oxidative stress and inflammation markers, and the expression of proteins related to apoptosis and inflammation signaling pathways.

Results: SLBZS markedly enhanced sperm quality, testicular and epididymal indices, and serum uric acid levels in mice, while ameliorating histopathological lesions in testicular tissue. Additionally, SLBZS significantly reduced oxidative stress, serum inflammation markers, and testicular cell apoptosis, with the high-dose group showing superior effects compared to the febuxostat group. Further investigation revealed that SLBZS inhibited the expression and phosphorylation of proteins in the MAPK/NF-κB pathway and suppressed the expression of proteins in the NLRP3 inflammasome pathway.

Discussion and conclusions: SLBZS potentially modulates the MAPK/NF-κB and NLRP3 inflammasome signaling pathways, thereby suppressing inflammatory responses and enhancing spermatogenesis in the testes of HUA mice.