Chinese medicine Sheng Jing Decoction alleviates oligoasthenospermia by modulating PI3K/Akt and MAPK signaling pathways.

BACKGROUND: Oligoasthenospermia (OAT), a major cause of male infertility, is characterized by reduced sperm count and motility, yet effective treatments remain limited. Sheng Jing Decoction (SJD), a clinically used traditional Chinese multi-herbal formulation developed by our team, has shown potential in improving sperm quality in animal models, but its molecular mechanisms have not been systematically elucidated.

METHODS: An OAT mouse model was established via intraperitoneal injection of triptolide (TP). SJD was administered by oral gavage for one month, beginning two days after TP treatment initiation. The chemical composition of SJD was characterized by ultra-high-performance liquid chromatography. Sperm concentration, motility, and testicular spermatogenic progression were evaluated with computer-assisted semen analysis (CASA) and hematoxylin and eosin (HE). Transcriptomic analysis was performed on testicular tissue, and apoptosis, oxidative stress, and inflammation were assessed. Key molecules in the PI3K/Akt and MAPK pathways were quantified using Western blot and RT-qPCR.

RESULTS: SJD significantly improved sperm concentration, motility, and overall quality, including the restoration of spermatogenic progression compared to the TP-treated group. Transcriptomic analysis revealed differentially expressed genes and enriched pathways related to spermatogenesis and sperm motility, consistent with phenotypic improvements. Mechanistically, SJD alleviated TP-induced testicular apoptosis, oxidative stress, and inflammation. Furthermore, SJD acts through the MAPK and PI3K/Akt signaling pathways, both of which are regulated by Ras as a common upstream regulator.

CONCLUSION: SJD effectively alleviates TP-induced OAT in mice by reducing testicular apoptosis, inflammation, and oxidative stress, as well as by restoring spermatogenesis, likely through modulation of the PI3K/Akt and MAPK signaling pathways. These findings provide mechanistic support for the potential application of SJD as a complementary therapeutic strategy for male infertility, especially that caused by environmental factors.