Amelioration of H2O2-induced post-weaning intestinal damage in piglets by terpinen-4-ol through enhanced epithelial renewal

Abstract Background This study evaluated the protective effects of terpinen-4-ol against H 2 O 2 ‑induced intestinal injury in weaned piglets and investigated the potential involvement of Wnt/β-catenin signaling. Thirty-two 28-day-old piglets were randomly divided into CON, TER, H 2 O 2 , and H + T groups. During a 21-day trial, H 2 O 2 and H + T groups received intraperitoneal injections of 10% H 2 O 2 on days 15 and 18, while CON and TER groups received saline injections. Intestinal morphology, proliferation and apoptosis of intestinal epithelial cells, and intestinal stem cell number and differentiation were assessed, and these changes were associated with modulation of Wnt/β-catenin signaling.​ Results Results indicated that H 2 O 2 challenge induced severe intestinal injury, manifested by reduced intestinal length, villus height, and villus height/crypt depth (V/C) ratio ( P < 0.01), alongside increased crypt depth. Specifically, terpinen-4-ol reversed the H 2 O 2 ‑induced downregulation of Ki67 expression​ ( P < 0.05) and inhibited the upregulation of Caspase‑3​ ( P < 0.01) in the small intestine. Furthermore, terpinen-4-ol restored H 2 O 2 ‑suppressed expression of stemness markers ( Lgr5 and Bmi1 ) and Lgr5 protein levels ( P < 0.05). Concurrently, terpinen-4-ol rescued goblet cell counts and the expression of secretory markers ( Muc2 , ChgA , Lyz ) and the enterocyte marker Villin ( P < 0.05), while enhancing Lyz protein levels ( P < 0.01). Notably, terpinen-4-ol was associated with upregulated Wnt/β‑catenin signaling ( P < 0.05), potentially accounting for mitigation of H 2 O 2 ‑induced inhibitory effects. Conclusions In conclusion, H 2 O 2 ‑induced intestinal injury was alleviated by terpinen-4-ol, as evidenced by​ enhanced epithelial renewal and restored stem cell homeostasis, with potential involvement of​ Wnt/β‑catenin signaling. These findings highlight the potential of terpinen-4-ol as a promising​ feed additive for mitigating oxidative stress‑associated intestinal dysfunction in swine production.