Dietary Stevia-Derived Isochlorogenic Acid Attenuates LPS-Induced Ileal Injury and Is Associated with Altered TLR4/MyD88/NF-κB and Nrf2/HO-1 Gene Expression in Weaned Lambs

Weaning stress-induced oxidative damage impairs lamb growth and health. This study explored the protective effects of stevia-derived isochlorogenic acid (ICGA) against lipopolysaccharide (LPS)-induced injury in 48 weaned lambs (50 ± 2 d old, 15 ± 2.30 kg), randomly allocated to four groups. CON and LPS groups received a basal diet; ICGA1 and ICGA2 received a basal diet with 1.5 and 2.0 g/kg ICGA for 14 d. On day 15, LPS (200 μg/kg BW) or saline was injected intraperitoneally. ICGA showed a trend to increase ADG (p > 0.05). ICGA reduced serum IL-6, TNF-α, IL-1β, DAO, D-LA, ET, and COR; elevated immunoglobulins; improved ileal morphology; upregulated tight junction genes and Nrf2/HO-1 pathway genes; and suppressed the TLR4/MyD88/NF-κB pathway. ICGA also modulated gut microbiota. In conclusion, ICGA alleviates inflammation and oxidative stress and improves intestinal barrier function in weaned lambs.