Perioperative sophocarpine protects against testicular ischemia/reperfusion injury by blocking JNK/p38 signaling

Testicular torsion is a common urological emergency; however, currently, there are no approved drugs to alleviate testicular ischemia/reperfusion (TI/R) injury. We investigated the protective effects and mechanisms of action of sophocarpine (SPC) as a potential preconditioning agent against TI/R injury. Bioinformatics analysis was used to predict SPC targets, followed by protein-protein interaction network construction and molecular docking. In vitro, oxygen-glucose deprivation/reperfusion (OGD/R)-treated GC-1 cells were used to assess apoptosis, reactive oxygen species (ROS), and c-Jun N-terminal kinase (JNK)/p38 phosphorylation. An in vivo rat TI/R model was established to evaluate histopathology, apoptosis, oxidative stress, and JNK/p38 signaling. Bioinformatics identified JNK and p38 as potential core targets with favorable binding affinities for SPC. SPC pretreatment significantly attenuated OGD/R- and TI/R-induced apoptosis and ROS accumulation, restored Bax/Bcl-2 balance and antioxidant enzyme activities, including that of superoxide dismutase, catalase, and glutathione peroxidase, and suppressed p38 phosphorylation. Cotreatment with anisomycin reversed these protective effects. SPC provides protection against TI/R injury through dual anti-apoptotic and antioxidant effects, with mechanistic evidence implicating inhibition of the JNK/p38 mitogen-activated protein kinase signaling pathway.