Celastrol in Rheumatoid Arthritis: Immunomodulatory Mechanisms, Multicellular Convergence, and Translational Challenges
5 affiliations
- 1Universidad de Guadalajara, Centro Universitario de Tonalá, Departamento de Ciencias Biomédicas, Centro de Investigación Multidisciplinario en Salud, Tonalá C.P. 45425, Jalisco, Mexico
- 2Universidad 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
- 3Universidad 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
- 4Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Boulevard V. Carranza S/N, Saltillo C.P. 25280, Coahuila, Mexico
- 5Laboratorio de Análisis Clínicos, El Hospital Regional de Alta Especialidad de Tlajomulco de Zúñiga del ISSSTE, Tlajomulco C.P. 45640, Jalisco, Mexico
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.
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BibTeX
@article{coronameraz2026celastrol,
title = {{Celastrol in Rheumatoid Arthritis: Immunomodulatory Mechanisms, Multicellular Convergence, and Translational Challenges}},
author = {Fernanda-Isadora Corona-Meraz and Beatriz Teresita Martín-Márquez and Luis E. Cobos-Puc and Elisa Guzmán-Alemán and Hilda Aguayo-Morales and Luis Daniel Hernández-Ortega and Roberto Carlos Rosales-Gómez and Rolando Castañeda-Arellano and Flavio Sandoval-García and Alvaro Jovanny Tovar-Cuevas},
journal = {International journal of molecular sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198834},
url = {https://europepmc.org/article/PMC/PMC13665401},
note = {CC BY},
}
RIS
TY - JOUR
TI - Celastrol in Rheumatoid Arthritis: Immunomodulatory Mechanisms, Multicellular Convergence, and Translational Challenges
AU - Fernanda-Isadora Corona-Meraz
AU - Beatriz Teresita Martín-Márquez
AU - Luis E. Cobos-Puc
AU - Elisa Guzmán-Alemán
AU - Hilda Aguayo-Morales
AU - Luis Daniel Hernández-Ortega
AU - Roberto Carlos Rosales-Gómez
AU - Rolando Castañeda-Arellano
AU - Flavio Sandoval-García
AU - Alvaro Jovanny Tovar-Cuevas
PY - 2026
DA - 2026/10/01
JO - International journal of molecular sciences
DO - 10.3390/ijms27198834
UR - https://europepmc.org/article/PMC/PMC13665401
AB - 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.
SN - 1422-0067
ER -