Hyperoside, a natural flavonoid compound, attenuates Triptolide-induced testicular damage by activating the Keap1-Nrf2 and SIRT1-PGC1α signalling pathway

OBJECTIVES: Hyperoside (Hyp), as the main ingredient from Semen Cuscutae, Abelmoschus moschatus, Acanthopanax senticosus, its protective effect in testicular dysfunction and mechanisms have not been studied. Here, we explored the action of Hyp in preventing oxidative stress-induced testicular damage and underlying mechanisms. METHODS: The testicular injury model caused by oxidative stress was successfully built via Triptolide (TP) intraperitoneal injection in male mice. After Hyp (12.5, 25 and 50 mg/kg/day) treatment, testes weights, sperm count and morphology, histological changes, oxidative stress biomarkers from testicular tissue were detected. Also, the molecular mechanism was investigated by western blotting and immunohistochemistry assay. KEY FINDINGS: These data suggested that Hyp significantly ameliorated TP-induced testicular atrophy, microstructural injury and spermatogenic dysfunction. Besides, it was shown that apoptosis-related proteins (cleaved caspase-3 and cleaved PARP) were prominently suppressed. The mechanical results indicated that Hyp significantly promoted Nrf2 translocation and elevated antioxidant enzymes expression in the testicular tissue. Meanwhile, this study also found that Hyp could improve TP-induced mitochondrial dysfunction via the SIRT1-PGC-1α signalling pathway. CONCLUSIONS: The present study indicated that Hyp exerted a potent ameliorative effect against testicular injury caused by oxidative stress via stimulating Keap1-Nrf2 and SIRT1-PGC1a signalling pathway.