{
  "abstract": "Background: Dysregulated buildup of extracellular matrix constitutes a hallmark of hepatic fibrosis, loss of liver architectural integrity, and impaired hepatic functional capacity. Pro-fibrogenic M2-polarized macrophages promote the transdifferentiation of hepatic stellate cells and facilitate fibrotic progression. Cannabidiol (CBD) exhibits immunomodulatory and anti-fibrotic properties. However, whether CBD regulates M2-like macrophage polarization to mitigate hepatic fibrogenesis remains unclear.\n\nObjective: Cannabidiol-driven mitigation of pathological hepatic remodeling was evaluated, with its molecular regulatory mechanisms systematically clarified.\n\nMethods: The modulation of liver fibrosis by cannabidiol was investigated in vitro and in vivo . A model was created using bile duct ligation (BDL). Anti-fibrotic effects were tested with liver function tests, histopathology, immunohistochemistry, and immunofluorescence. Co-culture systems comprising THP-1-derived macrophages and LX-2 stellate cells were constructed to delineate cannabidiol-mediated regulation of M2-like macrophage polarization and hepatic stellate cell transactivation. Transcriptomic, single-cell transcriptomic, network pharmacology, molecular docking simulation, and dynamic conformational approaches explored cannabidiol’s binding to TRPV4. Western blot, qRT-PCR, flow cytometry, CETSA, Co-IP, and mass spectrometry detected macrophage polarization and under-healing pathway markers. Transwell and colony-formation assays assessed the effects of conditioned medium from CBD-treated M2-like macrophages on LX-2 cell migration, proliferation, and activation.\n\nResults: Cannabidiol mitigated hepatic damage, fibrogenic progression, and inflammatory responses in BDL-operated mice, supported by ameliorated hepatic functional indices and reduced fibrotic biomarkers. CBD inhibited IL-4-induced M2-like polarization in THP-1 cells, resulting in decreased expression of M2-associated markers and pro-fibrotic factors. Mechanistically, CBD may engage TRPV4 and suppress RhoA/ROCK signaling, while concurrently modulating STAT6 phosphorylation. These molecular actions inhibited LX-2 cell activation, as indicated by reduced Col-I and α-SMA expression, along with diminished migration and proliferation. CBD further reduced collagen deposition and M2-associated macrophage infiltration in hepatic tissue. Notably, co-administration of CBD with a TRPV4 inhibitor potentiated anti-fibrotic effects both in vivo and in vitro .",
  "abstract_shown": true,
  "affiliations": [
    "Clinical Laboratory Center, The Affiliated Hospital of Guizhou Medical University",
    "Department of Medical Examination, Guizhou Medical University",
    "Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital Bijie Hospital"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Peiling Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yongmei Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Lian Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Manqin Yuan"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaosu Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ping He"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuping Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2wf1c4ymtdg6x.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1951332",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727404/?tool=EBI",
  "id": "2wf1c4ymtdg6x",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1951332/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2721|Liver physiology and pathology"
    ]
  ],
  "openalex": "W7223003026",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727404/pdf/?tool=EBI",
  "pmcid": "PMC13727404",
  "pmid": "42978588",
  "published": "2026-10-20",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/2wf1c4ymtdg6x.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1951332",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1951332/full"
    },
    {
      "first_seen": "2026-11-04T15:20:46Z",
      "native_id": "PMC:PMC13727404",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13727404"
    },
    {
      "first_seen": "2026-11-06T12:23:17Z",
      "native_id": "PMC13727404",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1951332"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Cannabidiol suppresses M2-like macrophage polarization via TRPV4/RhoA/ROCK signaling to alleviate hepatic fibrosis",
  "title_text": "Cannabidiol suppresses M2-like macrophage polarization via TRPV4/RhoA/ROCK signaling to alleviate hepatic fibrosis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:20:36Z",
  "url": "https://research.draconitic.com/paper/2wf1c4ymtdg6x",
  "venue": "Frontiers in Immunology",
  "versions": []
}