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June 27, 2026International Journal of Molecular Sciences0 citationsOpen Access

Exploring the Therapeutic Potential of Ganoderic Acid A Against Inflammatory Bowel Disease Based on Network Pharmacology, Molecular Docking, and Intestinal Organoid Validation

MCMin CaiThe People's Hospital of Guangxi Zhuang Autonomous Region MSManhui SunZhejiang University of Science and Technology KLKecheng LiZhejiang University of Science and Technology

Key Points

The study aims to explore the therapeutic mechanisms of ganoderic acid A against inflammatory bowel disease using network pharmacology and molecular docking.
Utilized a network pharmacology approach to identify potential targets and genes associated with inflammatory bowel disease.
Conducted molecular docking to analyze the binding affinity of ganoderic acid A to targeted proteins.
Validated key findings through experimental evaluation using intestinal organoid models.
Confirmed high-affinity binding of ganoderic acid A to five key targets with binding energies between −7.3 and −10 kcal/mol.
Observed significant suppression in levels of TNF-α and p-MAPK14 in organoids after ganoderic acid A treatment.
Identified 14 IBD-GAA-ferroptosis-related genes, providing insights into the multi-target effects of ganoderic acid A.

Abstract

Inflammatory bowel disease (IBD) poses a significant global health burden with rising incidence, particularly in Asia. This study employed an integrative network pharmacology approach combined with molecular docking to elucidate the therapeutic mechanism of ganoderic acid A (GAA) against IBD. Potential GAA targets were retrieved from pharmacogenomic databases, while IBD-related genes were curated from OMIM and GeneCards databases. Weighted gene co-expression network analysis of IBD transcriptomic datasets (GSE38713, GSE126124) identified disease-associated modules, with the yellow module exhibiting the strongest positive correlation. Functional enrichment analyses demonstrated significant involvement of overlapping targets in lipid metabolism, the inflammatory response, and the mitogen-activated protein kinase (MAPK) signaling cascade pathway. We identified 14 IBD-GAA-ferroptosis-related genes and 54 key module genes. Intersection analysis revealed 5 overlapping targets, including tumor necrosis factor-α(TNF-α), peroxisome proliferators-activated receptor γ (PPARγ), MAPK14, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic α (PIK3CA), and Caspase 3 (CASP3). Molecular docking confirmed high-affinity binding of GAA to these targets, with binding energies ranging from −7.3 to −10 kcal/mol. Crucially, experimental evaluation demonstrated the pivotal role of GAA in alleviating disease pathology. GAA treatment suppressed the significantly elevated levels of TNF-α and p-MAPK14 in the organoids using a cytokine/LPS-induced IBD model. These findings collectively suggest a potential involvement of GAA in pathways associated with ferroptosis regulation, although direct experimental evidence for ferroptosis markers remains to be established. The observed multi-target effects on immune regulation and cellular proliferation/differentiation provide a foundation for further mechanistic investigation.

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