Astragalus polysaccharides alleviate oxidative damage by activating the Keap1-Nrf2 antioxidant pathway through...

Astragalus polysaccharides (APS), one of the star antioxidants among traditional Chinese medicine, have widespread applications in healthcare, veterinary, and fishery fields. However, the mechanisms underlying their antioxidative action remain largely unknown. In this study, the protective role of APS in H₂O₂-induced oxidative damage and associated mechanism were investigated in large yellow croaker head kidney (LYCK) cells. We found that the APS significantly inhibited H₂O₂-induced cytotoxicity, ROS accumulation, and mitochondrial damage, thereby alleviating subsequent apoptosis and pyroptosis. Further studies showed that APS activated the Keap1-Nrf2 antioxidant signaling pathway, thus up-regulating the downstream antioxidant genes (SOD-1, CAT, HO-1, and GR), enhancing SOD-1 and CAT activities and T-AOC level, and decreasing MDA content. Mechanistically, APS activate this antioxidant signaling pathway by inducing the expression of microRNA-183 (miR-183-5p). The produced miR-183-5p binds to the 3'UTR of Keap1 mRNA and promotes its degradation, leading to consequent Nrf2 activation. Our results therefore unveil the mechanism by which APS alleviate oxidative damage in a fish cell model, and provide the theoretical basis for their application in aquaculture.