Network Pharmacology-Based Prediction and In Vivo Validation of Fumonisin B1-Induced Liver Injury and Early Fibrosis.

Fumonisin B1 (FB1) is a widespread mycotoxin contaminating food and feed, exhibiting severe hepatotoxicity. This study aimed to systematically investigate the underlying molecular mechanisms of FB1-induced liver injury and early liver fibrosis by combining network pharmacology with an in vivo animal model. First, network pharmacology and molecular docking were utilized to screen the core targets and key signaling pathways of FB1-induced hepatotoxicity. Subsequently, an in vivo C57BL/6 mouse model was established via intragastric administration of FB1 (5 mg/kg/day for 28 days). Serum levels of liver function and fibrosis markers (ALT, AST, HA, LN, PCIII, CIV) were measured. Histopathological changes and collagen deposition in liver tissues were evaluated using HE and Masson's trichrome staining. The relative mRNA expression of inflammation- (TNF-α, IL-1β, IL-6) and fibrosis-related core genes (TGF-β1, α-SMA, COL1A1) was quantified by qPCR. Network pharmacology predicted that inflammatory responses and fibrosis-related pathways are central to FB1 hepatotoxicity. In vivo experiments confirmed that FB1 exposure significantly elevated serum ALT and AST levels, as well as the four indices of liver fibrosis (p < 0.001). Histopathology revealed severe hepatocyte necrosis, inflammatory cell infiltration, and massive deposition of blue-stained collagen fibers. Furthermore, qPCR results demonstrated that FB1 significantly upregulated the expression of pro-inflammatory cytokines, strongly activated the TGF-β1 signaling pathway, and promoted the high expression of the hepatic stellate cell (HSC) activation marker (α-SMA) and extracellular matrix (COL1A1). In conclusion, FB1 drives the pathogenesis of early liver fibrosis by inducing sustained hepatic inflammation and activating the TGF-β1 signaling pathway, which promotes HSC activation and excessive extracellular matrix deposition. This study provides a vital theoretical basis for elucidating the target-organ toxicity mechanisms of mycotoxins and identifying potential interventions.