Astragaloside IV mitigated cadmium-induced glandular gastric injury in ducks by inhibiting PANoptosis.

Background: Cadmium (Cd), a nonessential heavy metal, threatens poultry health through environmental bioaccumulation; however, its adverse effects on the glandular stomach (GS), a critical digestive and immune organ in waterfowl, remain understood. The present study was designed to assess the gastroprotective potential of astragaloside IV (AS-IV), a naturally occurring triterpenoid saponin from Methods: Ducks received long-term dietary AS-IV pretreatment prior to Cd challenge, and GS pathological, biochemical, and molecular analyses were subsequently performed. Results: AS-IV pretreatment significantly ameliorated Cd-induced pathological lesions, including glandular tubular architecture disruption, epithelial cell swelling, vacuolar degeneration, basement membrane sloughing, and mucosal necrosis, while reducing the GS index. Biochemically, AS-IV restored antioxidant enzyme activities, reduced lipid peroxidation, and downregulated pro-inflammatory cytokine production. At the molecular level, AS-IV downregulated the expression of pivotal biomarkers associated with apoptosis, pyroptosis, and necroptosis in GS cells. Bioinformatic analysis of protein-protein interactions additionally indicated plausible links between Sirt3 signaling cascades and PANoptosis-related mechanisms. Conclusion: Collectively, these results reveal that prophylactic dietary supplementation with AS-IV confers protective efficacy against cadmium-triggered glandular gastric damage in ducks, conceivably via the regulation of PANoptosis-associated pathways mediated by Sirt3. Such evidence underscores the potential of botanical extracts as a viable strategy for safeguarding gastrointestinal integrity in waterfowl exposed to heavy metal-induced toxicity.