{
  "abstract": "Background Metabolic liver disease is closely linked to chronic inflammation and dysregulation of the gut–liver axis. Plant-derived flavonoids may influence these interconnected pathways through multi-target molecular interactions. Caesalpinia sappan, a traditional medicinal plant rich in polyphenolic flavonoids, has demonstrated anti-inflammatory and metabolic regulatory effects. However, the systems-level mechanisms underlying its potential impact on gut–liver signaling remain unclear.Methods Sixteen flavonoids representative of the phytochemical profile of C. sappan were identified from phytochemical databases and literature sources. Potential protein targets were predicted using BATMAN-TCM, HERB, SwissTargetPrediction, and NetInfer. Disease-associated genes related to fatty liver disease, metabolic disorders, inflammation, and skin diseases were retrieved from GeneCards and intersected with predicted compound targets. Functional enrichment analyses were conducted using Gene Ontology, KEGG, and Reactome databases. Protein–protein interaction networks and functional clusters were identified using STRING and Metascape.Results A total of 703 potential protein targets were identified for the 16 flavonoids. Intersection analysis revealed overlap between compound targets and genes associated with metabolic liver disease and inflammatory pathways. Enrichment analyses highlighted pathways related to PI3K–Akt, MAPK, AMPK, TNF, and AGE–RAGE signaling, which regulate lipid metabolism, inflammatory responses, and oxidative stress. Protein–protein interaction networks identified clusters involved in cytokine signaling and lipid metabolic processes. Cross-system analysis identified 18 shared genes across gut, liver, brain, and skin networks, suggesting coordinated multi-organ regulatory mechanisms relevant to the gut–liver axis.Conclusions Sappan flavonoids may modulate key signaling pathways linking inflammation, lipid metabolism, and gut–liver communication. These findings provide mechanistic insights supporting further investigation of C. sappan flavonoids as potential nutraceutical agents for metabolic liver disease.",
  "authors": [
    {
      "affiliations": [
        "Center of Excellence in Immunology and Immune-mediated Diseases, Faculty of Medicine, Chulalongkorn University, Thailand"
      ],
      "name": "May Soe Thu"
    },
    {
      "affiliations": [
        "Center of Excellence in Preventive and Integrative Medicine (CE-PIM), Faculty of Medicine, Chulalongkorn University, Thailand"
      ],
      "name": "Krit Pongpirul"
    },
    {
      "affiliations": [
        "Shanghai University of Traditional Chinese Medicine, China"
      ],
      "name": "Jian Chen"
    },
    {
      "affiliations": [
        "Center of Excellence in Preventive and Integrative Medicine (CE-PIM), Faculty of Medicine, Chulalongkorn University, Thailand"
      ],
      "name": "Thunnicha Ondee"
    },
    {
      "affiliations": [
        "Department of Thai Traditional and Alternative Medicine, Ministry of Public Health, Thailand"
      ],
      "name": "Kamonwan Banchuen"
    },
    {
      "affiliations": [
        "Institute of Nutrition, Mahidol University, Thailand"
      ],
      "name": "Kanchaporn Chaisungnern"
    },
    {
      "affiliations": [
        "Institute of Nutrition, Mahidol University, Thailand"
      ],
      "name": "Sayamon Senaprom"
    },
    {
      "affiliations": [
        "Research Affairs, Faculty of Medicine, Chulalongkorn University, Thailand"
      ],
      "name": "Phanupong Phutrakool"
    },
    {
      "affiliations": [
        "Center of Excellence in Preventive and Integrative Medicine (CE-PIM), Faculty of Medicine, Chulalongkorn University, Thailand"
      ],
      "name": "Oranut Chatsirisakul"
    },
    {
      "affiliations": [
        "Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Faculty of Medicine, Chulalongkorn University, Thailand"
      ],
      "name": "Asada Leelahavanichkul"
    },
    {
      "affiliations": [
        "Center of Excellence in Applied Thai Traditional Medicine Research (CEATMR), Thammasat University, Thailand"
      ],
      "name": "Arunporn Itharat"
    }
  ],
  "title": "IDDF2026-ABS-0231 Network pharmacology analysis of caesalpinia sappan flavonoids identifies gut-liver axis signaling pathways relevant to metabolic liver disease",
  "uid": "9da22c5b-45c0-56a6-9828-100b65d30e85"
}