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<p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing mucosal inflammation. Medicine-food homologous (MFH) substances represent a promising source of therapeutic compounds. This study aimed to identify promising key MFH-derived bioactives for UC intervention. Transcriptomic datasets from GEO were analyzed to overlap differentially expressed genes (DEGs) between UC and controls with UC-related target genes from public disease databases, generating candidate genes for functional enrichment analysis. Bioactive compounds from 110 MFH substances were compiled via dual-database integration. Compound–protein interactions were predicted using GraphBAN, followed by drug-likeness and toxicity evaluations to identify candidate key compounds and their corresponding potential key genes. An MFH substance–compound–gene tripartite network was constructed. Molecular docking and molecular dynamics (MD) simulations were performed, and the expression of candidate key genes was assessed in an independent UC/control tissue dataset. We identified 266 candidate genes enriched in immune response, inflammation, and cell adhesion pathways. MOL008417 was prioritized as the candidate key compound, with CHRM3, CYP17A1, CYP3A5, MPO, and NOS1 prioritized as potential key genes. Network analysis highlighted Dangshen (<i>Codonopsis</i> root) as a key MFH substance. Docking suggested a feasible binding between MOL008417 and CHRM3 (− 5.3 kcal/mol), and MD simulations indicated complex stability. Gene expression analysis demonstrated significant CHRM3 upregulation and CYP3A5 downregulation in inflamed UC tissues compared with non-inflamed UC tissues and control samples. Our integrated computational workflow suggests that the MFH-derived compound MOL008417 may have multi-target potential for UC treatment through interactions with potential key genes. These predictive findings offer a mechanistic hypothesis for the development of MFH-based interventions and could inform the design of novel, UC therapeutics, pending future experimental validation.</p> Graphical Abstract <p></p>

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Identification of key bioactive compounds of medicine-food homologous substances and their multi-target intervention effects in ulcerative colitis treatment

  • 期刊论文

  • 发表日期：

    2026年2月6日

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  • Wenhan Wu,
  • Jinjin Li,
  • Jun Zhang,
  • Zhen Huang

摘要

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing mucosal inflammation. Medicine-food homologous (MFH) substances represent a promising source of therapeutic compounds. This study aimed to identify promising key MFH-derived bioactives for UC intervention. Transcriptomic datasets from GEO were analyzed to overlap differentially expressed genes (DEGs) between UC and controls with UC-related target genes from public disease databases, generating candidate genes for functional enrichment analysis. Bioactive compounds from 110 MFH substances were compiled via dual-database integration. Compound–protein interactions were predicted using GraphBAN, followed by drug-likeness and toxicity evaluations to identify candidate key compounds and their corresponding potential key genes. An MFH substance–compound–gene tripartite network was constructed. Molecular docking and molecular dynamics (MD) simulations were performed, and the expression of candidate key genes was assessed in an independent UC/control tissue dataset. We identified 266 candidate genes enriched in immune response, inflammation, and cell adhesion pathways. MOL008417 was prioritized as the candidate key compound, with CHRM3, CYP17A1, CYP3A5, MPO, and NOS1 prioritized as potential key genes. Network analysis highlighted Dangshen (Codonopsis root) as a key MFH substance. Docking suggested a feasible binding between MOL008417 and CHRM3 (− 5.3 kcal/mol), and MD simulations indicated complex stability. Gene expression analysis demonstrated significant CHRM3 upregulation and CYP3A5 downregulation in inflamed UC tissues compared with non-inflamed UC tissues and control samples. Our integrated computational workflow suggests that the MFH-derived compound MOL008417 may have multi-target potential for UC treatment through interactions with potential key genes. These predictive findings offer a mechanistic hypothesis for the development of MFH-based interventions and could inform the design of novel, UC therapeutics, pending future experimental validation.

Graphical Abstract