Tianjihuang compound alleviates aflatoxin B1-induced hepatic steatosis and fibrosis by targeting PPARα-TGF-β pathway in ducklings

Aflatoxin B₁ (AFB₁), a potent mycotoxin, poses a significant threat to the poultry industry, particularly affecting the health and growth of ducklings. The present study aimed to investigate the therapeutic effects and mechanisms of the Tianjihuang compound (HRS), a traditional Chinese medicine formulation, on AFB₁-induced chronic toxicity in ducklings. Firstly, 30 ingredients, including neochlorogenic acid, kaempferol 3-alpha-D-galactoside, quercetin, hispidulin, caffeic acid, and myricetin, were identified from HRS with UPLC-MS/MS method. Then, over a 25-day experimental period, a total of 100 one-day-old Sichuan Sheldrakes were randomly divided into five groups: control, AFB₁ model, and HRS high (4 g/kg), medium (2 g/kg), and low dosage (1 g/kg) groups. Results indicated that HRS effectively mitigated the negative impact on the productivity, reduced the levels of liver index, AST, ALT, and AST/ALT in serum, increased the levels of serum TP content, and obviously alleviated inflammatory cell infiltration, liver fibrosis, and liver steatosis induced by AFB₁. Additionally, HRS enhanced the levels of GST, CAT, and T-AOC, and decreased the levels of MDA and AFB₁-DNA, thereby alleviating oxidative stress and AFB₁-DNA generation caused by AFB₁. Transcriptome analysis revealed that HRS may improve liver injury in AFB₁-chronically poisoned ducklings by regulating the ECM receptor interaction, fatty acid metabolism, cell adhesion molecules, TGF-β signaling pathway, and PPAR signaling pathway. Further RT-qPCR analysis revealed that HRS might downregulate the expression of ASCL4 gene by promoting the activation of PPARα, thereby inhibiting the activation of the TGF-β signaling pathway and improving liver steatosis and fibrosis caused by AFB₁ in ducklings. In conclusion, the HRS exhibits hepatoprotective effects against AFB₁-induced chronic toxicity in ducklings by restoring liver function, enhancing antioxidant capacity, and its mechanism of damage resistance may be related to the improvement of liver steatosis and fibrosis in ducklings by inhibiting the PPARα-TGF-β signaling pathway.