A novel traditional Chinese medicine compound alleviates broiler ascites syndrome by modulating the IL-6/STAT3/FOXO3a signaling pathway

Broiler ascites syndrome (BAS), a non-infectious group disease caused by relative hypoxia in broilers, is one of the three most serious nutritional metabolic diseases that jeopardize the chicken industry. At present, traditional Chinese medicine (TCM) is widely used to treat BAS, however, its mechanism of action remains unclear. Therefore, this study aimed to screen a new traditional Chinese medicine compound (NCMC) for the treatment of BAS and to elucidate its therapeutic mechanism through an integrated strategy of data mining, network pharmacology, molecular docking, and animal experiments. To this end, a novel NCMC comprising Poria, Pericarpium Citri Reticulatae, Radix Scutellariae, Radix Astragali, Semen Plantaginis, and Rhizoma Zingiberis Recens was successfully formulated based on data mining analysis. Utilizing network pharmacology, STAT3, SRC, and EGFR were identified as core therapeutic targets for BAS. Gene pathway analysis further suggested that the NCMC might exert its effects by modulating hypoxia response, oxidative stress, and the FOXO signaling pathway. These in silico predictions were subsequently validated by in vivo experiments, which demonstrated that NCMC treatment significantly alleviated systemic inflammation, reduced the ascites heart index, and mitigated lung tissue damage in broilers. Concurrently, it markedly enhanced the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) while decreasing the content of malondialdehyde (MDA) in lung tissue. Ultimately, our integrated research approach revealed that the therapeutic effect of NCMC against BAS is primarily achieved through inhibition of the IL-6/STAT3/FOXO3a signaling pathway activation. This study not only provides a promising candidate drug for the treatment of BAS, but also offers a feasible systems pharmacology paradigm for modern research on traditional Chinese medicine compounds.