{
  "abstract": "Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is driven by dysregulated lipid metabolism, oxidative stress, and chronic inflammation. Botanical bioactives capable of modulating multiple pathogenic pathways may offer therapeutic potential. Mulberry leaf (Morus alba L.), traditionally used for metabolic disorders, contains diverse phytochemicals with reported metabolic and anti-inflammatory effects. This study aimed to explore the systems-level mechanisms by which mulberry leaf bioactives may influence MASLD-related pathways.Methods Bioactive compounds of mulberry leaf were retrieved from the HERB database and filtered to retain water-soluble constituents. Potential protein targets were predicted using INPUT and NetInfer and standardized using UniProt identifiers. MASLD-related gene sets were obtained from GeneCards and integrated with gene sets linked to metabolic and inflammatory pathways. Overlapping targets between mulberry compounds and disease-associated genes were identified and analyzed using Gene Ontology (GO), KEGG, and Reactome enrichment analyses. Protein–protein interaction networks were constructed to identify functional clusters.Results The analysis identified 151 water-soluble compounds associated with 1,265 predicted protein targets. Intersection analysis revealed substantial overlap between mulberry targets and MASLD-related genes, including pathways involved in inflammation and lipid metabolism. Enrichment analyses highlighted key biological processes related to inflammatory response, lipid metabolic regulation, and cellular stress responses. Major enriched pathways included TNF signaling, PI3K–AKT signaling, AMPK signaling, apoptosis, and AGE–RAGE signaling in diabetic complications. Reactome analysis further indicated cytokine-mediated signaling and lipid metabolism pathways. Network analysis identified functional modules associated with lipid metabolism and immune regulation.Conclusions Mulberry leaf bioactives may influence MASLD through coordinated modulation of inflammatory signaling and lipid metabolic pathways. These findings provide systems-level mechanistic support for the potential role of Morus alba–derived bioactives in metabolic liver disease.",
  "authors": [
    {
      "affiliations": [
        "Center of Excellence in Immunology and Immune-mediated Diseases, Faculty of Medicine, Chulalongkorn University, Thailand"
      ],
      "name": "Mae 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-0233 Multi-target mechanisms of morus ALBA leaf bioactives in metabolic dysfunction-associated steatotic liver disease: a network pharmacology study",
  "uid": "63f9f4ca-a276-5b87-904d-42f645bfd3a2"
}