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The objective of this study was to explore the mechanism of Hedyotis diffusa (HD) in mediating the detoxification of aflatoxin B 1 (AFB 1 )-induced hepatic injury in chicks. A total of 144 one-day-old male broilers (Cobb 500) were randomly assigned to four treatment groups ( n = 6 cages/diet, 6 chicks/cage). After three days of acclimation, the broilers were fed either a control diet (Control), Control plus 0.5 mg/kg of AFB 1 , or Control plus 0.5 mg/kg AFB 1 with 500 or 1000 mg/kg HD for two weeks. Both serum and liver were collected at the end of the feeding trial for biochemistry, histology, and NF-E2-related nuclear factor 2 (NRF2)/antioxidant response element (ARE) signaling analysis. Compared with Control, the AFB 1 treatment caused liver injury and decreased ( p &lt; 0.05) body weight gain, feed intake, feed conversion ratio, and serum albumin and total protein by 6.2-20.7%. AFB 1 also induced swelling, necrosis, and severe vacuolar degeneration in chicks' livers. Notably, HD supplementation at 500 and 1000 mg/kg mitigated ( p &lt; 0.05) the alterations induced by AFB 1 . HD supplementation alleviated ( p &lt; 0.05) AFB 1 -induced impairment in hepatic glutathione peroxidase activity, protein carbonyl, and exo-AFB 1 -8,9-epoxide (AFBO)-DNA concentrations by 57.7-100% and increased ( p &lt; 0.05) the activities of superoxide dismutase and catalase by 23.1-40.9% more than those of AFB 1 treatment alone. Furthermore, HD supplementation at the two doses upregulated ( p &lt; 0.05) NRF2, NAD(P)H: quinone oxidoreductase-1, heme oxygenase-1, glutathione cysteine ligase catalytic subunit, and glutathione-S transferase A2 and A3 in livers relative to the AFB 1 group by 0.99-3.4-fold. Overall, dietary supplementation of HD at a high dose displayed better protection effects against aflatoxicosis. In conclusion, a dietary HD supplementation at 500 and 1000 mg/kg protected broilers from AFB 1 -induced hepatotoxicity, potentially due to the activation of NRF2/ARE signaling in the chicks.

Mitigation of Aflatoxin B1 Hepatoxicity by Dietary Hedyotis diffusa Is Associated with Activation of NRF2/ARE Signaling in Chicks