Network Pharmacology and In Vivo Evaluation of Lycium barbarum Polysaccharide in Preventing Perfluorooctanoic Acid-Induced Damage in Broilers.

Abstract

To examine the guarding effects of Lycium barbarum polysaccharides (LBP) on liver and gut injury induced by perfluorooctanoic acid (PFOA) in broilers. Initially, a dose selection experiment for PFOA modeling was conducted. A total of 160 one-day-old broilers were randomly assigned to four groups. The drinking water was supplemented with 0 mg/L PFOA (CON group), 0.5 mg/L PFOA (L-PFOA group), 1 mg/L PFOA (M-PFOA group), and 1.5 mg/L PFOA (H-PFOA group). The results indicated that compared to the CON group, the H-PFOA group showed significant increases liver function indicators, while antioxidant enzyme levels were significantly downregulated. Additionally, the H-PFOA group exhibited significant damage to the liver and intestinal tissue morphology. Subsequently, network pharmacology methods were employed to identify target protein information for LBP in preventing PFOA-induced damage. Protein-protein interaction analysis, GO functional annotation, and KEGG pathway enrichment analysis were performed. The network pharmacology results revealed a total of 100 key protein targets, with core targets mainly enriched in the AGE-RAGE and FOXO signaling pathways. Finally, animal experiments were conducted to verify. A total of 240 one-day-old broilers were randomly divided into six groups: CON group as blank control, PFOA group supplemented with 1.5 mg/L PFOA, l-LBP, M-LBP, and H-LBP groups further supplemented with 0.4 %, 0.6 %, and 0.8 % LBP respectively on a base of 1.5 mg/L PFOA, with LBP group as a control supplemented only with 0.8 % LBP in water. The results demonstrated that versus the CON group, the H-LBP group dropped considerably in daily weight gain, liver index, and pro-inflammatory cytokine levels, while antioxidant enzyme levels and intestinal tight junction protein mRNA expression were significantly upregulated. Moreover, the H-LBP group showed significant improvement in liver and intestinal tissue morphology. qPCR results revealed that PFOA exposure activated the AKT/FOXO1 signaling pathway, which was inhibited by LBP. In conclusion, LBP prevent PFOA-induced damage via a multi-component, multi-target, and multi-pathway mechanism.