{
  "abstract": "Rheumatoid arthritis (RA) arises from interactions among immune, stromal, and osteoimmune compartments, supporting interest in agents with multilevel activity, such as celastrol. This narrative review critically integrates evidence on its chemical–pharmacological basis, immunomodulatory mechanisms, cellular effects, and translational potential in RA. Preclinical data show inhibition of inflammatory programs in macrophages and neutrophils, modulation of T- and B-cell responses, suppression of pathogenic fibroblast-like synoviocyte (FLS) functions, and reduced osteoclastogenesis and structural damage. COMM domain-containing proteins 3 and 8 (COMMD3/8) provide the strongest causal validation, while insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) has biophysical and functional support; numerous inflammatory and metabolic nodes primarily represent downstream signaling. Multicellular models support functional convergence, but intercellular causation in RA remains limited; directional functional evidence for dendritic cell–T-cell modulation comes from non-rheumatoid models, and no persistent synovial reprogramming has been demonstrated. Low bioavailability, multitarget covalent pharmacology, a narrow therapeutic window, and contributions from delivery carriers constrain translational interpretation. Addressing these translational challenges explicitly can help guide future research to improve celastrol’s safety and efficacy, which is essential for clinical application.",
  "abstract_shown": true,
  "affiliations": [
    "Universidad de Guadalajara, Centro Universitario de Tonalá, Departamento de Ciencias Biomédicas, Centro de Investigación Multidisciplinario en Salud, Tonalá C.P. 45425, Jalisco, Mexico",
    "Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Departamento de Biología Molecular y Genómica, Instituto de Investigación en Reumatología y Sistema Músculo Esquelético, Guadalajara C.P. 44340, Jalisco, Mexico",
    "Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Departamento de Biología Molecular y Genómica, Cuerpo Académico UDG-CA-703 “Inmunología y Reumatología”, Guadalajara C.P. 44340, Jalisco, Mexico",
    "Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Boulevard V. Carranza S/N, Saltillo C.P. 25280, Coahuila, Mexico",
    "Laboratorio de Análisis Clínicos, El Hospital Regional de Alta Especialidad de Tlajomulco de Zúñiga del ISSSTE, Tlajomulco C.P. 45640, Jalisco, Mexico"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Fernanda-Isadora Corona-Meraz",
      "orcid": "0000-0002-7267-1482"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Beatriz Teresita Martín-Márquez",
      "orcid": "0000-0002-6756-4316"
    },
    {
      "affs": [
        3
      ],
      "name": "Luis E. Cobos-Puc",
      "orcid": "0000-0002-9593-7562"
    },
    {
      "affs": [
        4
      ],
      "name": "Elisa Guzmán-Alemán",
      "orcid": "0009-0004-9404-1643"
    },
    {
      "affs": [
        3
      ],
      "name": "Hilda Aguayo-Morales",
      "orcid": "0000-0001-9597-9714"
    },
    {
      "affs": [
        0
      ],
      "name": "Luis Daniel Hernández-Ortega",
      "orcid": "0000-0003-2285-4376"
    },
    {
      "affs": [
        0
      ],
      "name": "Roberto Carlos Rosales-Gómez",
      "orcid": "0000-0003-4478-1729"
    },
    {
      "affs": [
        0
      ],
      "name": "Rolando Castañeda-Arellano",
      "orcid": "0000-0001-6940-5899"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Flavio Sandoval-García",
      "orcid": "0000-0001-9251-4209"
    },
    {
      "affs": [
        0
      ],
      "name": "Alvaro Jovanny Tovar-Cuevas",
      "orcid": "0000-0002-0394-6737"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/37vp5k072bkdm.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198834",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665401/?tool=EBI",
  "id": "37vp5k072bkdm",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13665401",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2707|Natural Compounds in Disease Treatment"
    ]
  ],
  "openalex": "W7220406430",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665401/pdf/?tool=EBI",
  "pmcid": "PMC13665401",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/37vp5k072bkdm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:31Z",
      "native_id": "PMC:PMC13665401",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13665401"
    },
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27198834",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/19/8834"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2707|Natural Compounds in Disease Treatment",
      "subfield": "general"
    }
  ],
  "title": "Celastrol in Rheumatoid Arthritis: Immunomodulatory Mechanisms, Multicellular Convergence, and Translational Challenges",
  "title_text": "Celastrol in Rheumatoid Arthritis: Immunomodulatory Mechanisms, Multicellular Convergence, and Translational Challenges",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:55Z",
  "url": "https://research.draconitic.com/paper/37vp5k072bkdm",
  "venue": "International journal of molecular sciences",
  "versions": []
}