Molecular Mechanisms of Quercetin in Regulating Antioxidant Defense and Pyroptosis Pathways in the Redclaw Crayfish (Cherax quadricarinatus)

As a principal species in freshwater aquaculture, the redclaw crayfish (Cherax quadricarinatus) depends on a competent immune system to mitigate environmental and pathogenic challenges. Quercetin, a ubiquitous plant-derived flavonoid, has garnered scientific attention due to its pleiotropic bioactivities, including antioxidant, anti-inflammatory, and immunomodulatory properties. This study investigated the effects of waterborne quercetin exposure on transcriptional regulation and antioxidant capacity in C. quadricarinatus. Over a 28-day period, crayfish were subjected to five quercetin concentrations (0, 1.0, 2.5, 5.0, and 10.0 mg/L), with outcomes evaluated against an untreated control. At the concentration of 5.0 mg/L, which showed the most pronounced effects among the tested concentrations, quercetin exposure was associated with significant downregulation of key transcripts in the NLRP3 inflammasome pathway (NLRP3, GSDMD, Caspase-1), as evidenced by the downregulation of NLRP3, GSDMD, and Caspase-1. Simultaneously, the transcriptional changes were consistent with the modulation/activation of the Nrf2 signaling axis, upregulating the expression of Nrf2, NQO1, and Keap1. These transcriptional changes indicate that quercetin attenuates pyroptosis and augments cellular antioxidant defenses via the Nrf2-Keap1 cascade. Correspondingly, the hepatopancreas displayed markedly elevated activities of SOD, CAT, and GSH-Px, accompanied by a significant reduction in MDA levels, indicating enhanced antioxidative capacity and diminished lipid peroxidation. This study provides valuable toxicological insights and elucidates part of the molecular basis for quercetin's immunomodulatory and antioxidant roles in freshwater crustaceans.