Agaricus bisporus polysaccharide ABP alleviates X-ray-induced spermatogonial injury via the PI3K/AKT/mTOR pathway: toward a novel dietary radioprotectant

Polysaccharides from edible mushrooms are promising dietary ingredients for functional foods due to their potent antioxidant and cytoprotective activities. Given the scarcity of safe and effective dietary strategies against X-ray-induced male reproductive system damage, this study investigated the potential of a polysaccharide from Agaricus bisporus (ABP) to protect mouse spermatogonial GC-1 cells, focusing on the PI3K/AKT/mTOR pathway, a key signaling axis known to be modulated by various bioactive food components. In an in vitro irradiation model, ABP pretreatment significantly improved the cell viability, reduced ROS accumulation, suppressed the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and pro-apoptotic genes (Caspase-3, Caspase-8, Bax), and upregulated the anti-apoptotic gene Bcl-2. Western blotting and qPCR further confirmed alterations in pathway-related molecules, and validation with the inhibitors LY294002 and rapamycin demonstrated that ABP restored the phosphorylation of PI3K, AKT, and mTOR, whereas pathway inhibition abolished its protective effects. Collectively, these findings indicate that ABP alleviates radiation-induced reproductive toxicity primarily through activation of the PI3K/AKT/mTOR pathway and attenuation of oxidative stress and apoptosis. This work provides mechanistic evidence supporting the development of ABP as a safe, natural dietary ingredient for functional foods aimed at mitigating radiation-associated reproductive health risks.