Mitigation of Aflatoxin B(1) Hepatoxicity by Dietary Hedyotis diffusa Is Associated with Activation of NRF2/ARE Signaling in Chicks

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 < 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 < 0.05) the alterations induced by AFB(1). HD supplementation alleviated (p < 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 < 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 < 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.