Mechanism of tea saponin regulating the Nrf2/HO-1/NQO1 pathway to alleviate Salmonella Enteritidis-induced intestinal pathological injury in chicks.

Previous studies have demonstrated that Salmonella Enteritidis triggers intestinal pyroptosis and pathological damage in hosts. Tea saponin (Ts) exhibits favorable anti-inflammatory, antioxidant and intestinal barrier-protective activities, whereas its protective role and molecular mechanism against Salmonella Enteritidis-induced intestinal injury in chicks remain poorly elucidated. This study explored the protective effects of Ts on Salmonella Enteritidis-caused intestinal damage in chicks and whether the Nrf2/HO-1/NQO1 signaling pathway mediates its function. A total of 60 7-day-old specific pathogen-free (SPF) chicks were randomly assigned to six groups: control, Salmonella Enteritidis-infected model, low, medium and high-dose Ts intervention groups, and florfenicol positive control group. Except the control group, all chicks received intraperitoneal Salmonella Enteritidis injection for model establishment, followed by 7 consecutive days of corresponding treatments. Diarrhea score, histopathological changes in the ileum and liver, serum liver function parameters (ALT, AST, ALP, TBIL), oxidative stress markers (SOD, GSH‑PX, CAT, MDA), and inflammatory cytokines (TNF‑α, IL‑6, IL‑1β, IL‑10) were measured, and the expression levels of Nrf2/HO‑1/NQO1 pathway components were evaluated at both mRNA and protein levels. Network pharmacology combined with molecular docking further validated the binding relationship between Ts and pathway key proteins. The untreated infected group presented aggravated diarrhea, severe intestinal and hepatic lesions, disordered liver function, oxidative stress and inflammation, along with suppressed Nrf2/HO‑1/NQO1 pathway expression. Ts intervention reversed these damages dose‑dependently, with high‑dose Ts showing the optimal efficacy. In conclusion, Ts mitigates diarrhea, inflammation and visceral pathological injury in Salmonella Enteritidis‑infected chicks, and its effects are associated with activation of the Nrf2/HO‑1/NQO1 pathway, improved antioxidant defense and inhibited inflammatory responses.