Rosa roxburghii juice alleviates DEHP-induced reproductive system damage in male mice via the PI3K/AKT signaling pathway

Ethnopharmacological relevance Rosa roxburghii is an ethnic medicinal herb. Folk medicine collections have documented its nourishing and strengthen effects. It has been used to improve reproductive health, but scientific evidence supporting its efficacy and mechanisms remains limited. Aim of this study Endocrine-disrupting chemicals, such as di-(2-ethylhexyl) phthalate (DEHP), are known to impair male reproductive health. This study aims to investigate the protective effects of raw Rosa roxburghii juice (RRJ) on DEHP-induced reproductive toxicity in mice and elucidates its underlying mechanisms. Materials and methods Using a DEHP-induced murine model of reproductive damage, we evaluated the effects of RRJ on sperm quality, testicular histopathology, reproductive endocrine function, oxidative stress, inflammation, apoptosis, and DNA damage. Network pharmacology analysis was performed to identify the active components, targets, and mechanisms underlying the therapeutic effects of Rosa Roxburghii . Results Our data demonstrated that RRJ significantly improved sperm quality, alleviated testicular atrophy, restored endocrine disorders, and mitigated oxidative stress, inflammation, and apoptosis in testicular tissues. Additionally, RRJ reduced testicular and sperm DNA damage, as evidenced by decreased γ-H2AX expression and DNA fragmentation index. Network pharmacology analysis identified quercetin, apigenin, luteolin, kaempferol, eriodictyol, and ellagic acid as the key bioactive compounds in RRJ, with the PI3K/AKT signaling pathway playing a crucial role in its therapeutic effects. Western blotting confirmed that RRJ reversed DEHP-induced suppression of the PI3K/AKT pathway. Conclusions This study demonstrates that RRJ protects against DEHP-induced reproductive toxicity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, mediated in part by the PI3K/AKT signaling pathway. This work provides the first comprehensive evidence of the protective effects of Rosa roxburghii against male reproductive system damage and its underlying mechanisms.