Network Pharmacology-Based Prediction and In Vivo Validation of Fumonisin B1-Induced Liver Injury and Early Fibrosis.
5 affiliations
- 1Department of Clinical Laboratory, Wuxi Maternity and Child Health Care Hospital, Affiliated Women's Hospital of Jiangnan University, Wuxi, Jiangsu, China.
- 2Intensive Care Unit, Jurong Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu, China.
- 3Department of Laboratory Medicine, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng, Jiangsu, China.
- 4Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
- 5Molecular Medical Research Center, Yancheng Clinical Medical College of Jiangsu University, Yancheng, Jiangsu, China.
Abstract
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.
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BibTeX
@article{li2026network,
title = {{Network Pharmacology-Based Prediction and In Vivo Validation of Fumonisin B1-Induced Liver Injury and Early Fibrosis.}},
author = {Na Li and Wen Sun and Xuehui Liu and Xinyu Liu and Yunhan Xie and Hao Xu and Linlin Xu and Jia Zang and Leilei Zhang and Liang Wu and Keke Shao},
journal = {Journal of biochemical and molecular toxicology},
year = {2026},
month = oct,
doi = {10.1002/jbt.71129},
url = {https://europepmc.org/article/MED/42852606},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Network Pharmacology-Based Prediction and In Vivo Validation of Fumonisin B1-Induced Liver Injury and Early Fibrosis.
AU - Na Li
AU - Wen Sun
AU - Xuehui Liu
AU - Xinyu Liu
AU - Yunhan Xie
AU - Hao Xu
AU - Linlin Xu
AU - Jia Zang
AU - Leilei Zhang
AU - Liang Wu
AU - Keke Shao
PY - 2026
DA - 2026/10/01
JO - Journal of biochemical and molecular toxicology
DO - 10.1002/jbt.71129
UR - https://europepmc.org/article/MED/42852606
AB - 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.
SN - 1095-6670
SN - 1099-0461
ER -