Yam-Active Protein Protects Against Cyclophosphamide-Induced Testicular Injury by Suppressing Inflammatory Responses

Chemotherapy-induced gonadotoxicity severely compromises male fertility, yet effective interventions remain limited. Building on our previous finding that yam protein (YP) modulates the gut-microbiota axis, this study investigated its direct protective role against cyclophosphamide (CTX)-induced testicular injury. Spectral analysis revealed a protein fraction (L-YP) with strong intrinsic fluorescence and optimal cytoprotection against oxidative stress. Proteomic characterization revealed six dominant proteins (YP1–YP6). In vivo experiments demonstrated that L-YP upregulates the expression of tight junction proteins Occludin and ZO-1, restores hormone levels, and modulates inflammatory factors, thereby enhancing the integrity of the blood–testis barrier. Network pharmacology analysis and molecular docking predicted a potential binding affinity between key components such as YP2 and NF-κB p65, which may provide a structural basis for their regulatory role. Further validation at the gene level indicated that YP can improve the local testicular immune microenvironment by modulating the classical TLR4/MyD88/NF-κB inflammatory signaling pathway. These findings suggest that yam protein alleviates chemotherapy-induced testicular damage, potentially through barrier protection and anti-inflammatory mechanisms, indicating its promise as a dietary protective agent.