Naringenin alleviates heat stress-induced thymic injury through a triple mechanism of immune modulation, antioxidant defense, and inflammation suppression.

The thymus is an important immune organ, and heat stress can significantly impact the immune function of chickens. Naringenin, as a novel immunomodulator, can restore the imbalanced immune state (pathological state) to a near-normal immune equilibrium (physiological state). This research aims to investigate the effects of naringin on heat stress-induced damage in the thymus of Ningdu Yellow chickens. Two hundred eighty-eight 28-day-old Ningdu yellow chickens were randomly assigned to four groups: control (Con), naringenin-supplemented (Con+Nar), heat stress (HS), and heat stress + naringenin (HS+Nar). HS and HS+Nar groups were subjected to cyclic temperatures daily (37 ± 2 °C, 07:00-19:00; 24 ± 2 °C, 19:00-07:00). Con+Nar and HS+Nar groups received diets supplemented with 200 mg/kg naringenin for 35 consecutive days. Results showed that naringenin significantly ameliorated heat stress-induced thymic pathological damage in Ningdu yellow chickens and reversed heat stress-reduced immune indices (IgA, IgG, IgM). Molecularly, heat stress markedly suppressed the Nrf2/Keap1 signaling axis, downregulated Nrf2, HO-1, and NQO1 expression, while activating NF-κB pathway key molecules (TLR4, MYD88), thereby upregulating pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17) and downregulating anti-inflammatory cytokine IL-10. In contrast, naringenin enhanced antioxidant capacity via modulating the Nrf2/Keap1 pathway and inhibited excessive pro-inflammatory factor elevation, consequently alleviating thymic injury. Overall, naringenin exerts multi-targeted regulation of oxidative stress-inflammation crosstalk, maintaining thymic immune microenvironment homeostasis under heat stress. These findings lay a theoretical basis for developing naringenin-based feed additives to prevent and control poultry heat stress syndrome.