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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Inflammation Pharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1705962

Regulation of inflammatory pathways by cannabigerol in the collagen induced arthritis model in rats

Provisionally accepted
Monika  ŠteigerováMonika Šteigerová1Michaela  SklenárováMichaela Sklenárová1Mykhaylo  BazyukMykhaylo Bazyuk1Luděk  ZáveskýLuděk Záveský1Petr  JelínekPetr Jelínek2Mahak  AroraMahak Arora1Daniel  StránskýDaniel Stránský1Tomáš  KučeraTomáš Kučera3Bruno  SepodesBruno Sepodes4Miroslav  ŠoóšMiroslav Šoóš2Martin  ŠímaMartin Šíma1*Ondrej  SlanarOndrej Slanar1*
  • 1Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czechia
  • 2Department of Chemical Engineering, Faculty of Chemical Engineering, University of Chemistry and Technology, Prague, Czech Republic, Prague, Czechia
  • 3Institute of Histology and Embryology, First Faculty of Medicine, Charles University, Prague, Czech Republic, Prague, Czechia
  • 4Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal, Lisbon, Portugal

The final, formatted version of the article will be published soon.

Abstract Objectives: This study aims to assess the anti-inflammatory properties of cannabigerol (CBG) in collagen-induced arthritis (CIA) model in rats, and to determine which inflammatory signaling pathways it affects. Study design: Rats were randomized into four groups: placebo (PCB) – p.o. treated with 1 mL of 0.9% saline once daily, CBG – p.o. treated with 30 mg of CBG/day, glucocorticoids (GC) – p.o. treated with methylprednisolone 0.5 mg/kg/day, and negative control (CO) – p.o. treated with 1 mL of 0.9% saline once daily. CIA was induced in the PCB, GC, and CBG groups. The effect of CBG was assessed by clinical scoring, paw width measurements, ELISA, and analysis of gene (qPCR) and protein (Western blot) expression of selected inflammatory markers in blood and synovial membrane. Results: Clinical scores showed significant improvement in the CBG vs. PCB on day 29 and in the GC vs. PCB on days 24, 27, and 29. MMP-3 levels in serum were significantly reduced in the GC vs. PCB. CBG demonstrated a selective anti-inflammatory and immunomodulatory profile, notably through the downregulation of key signaling molecules such as TLRs, systemic NF-κB p65, STAT-3, and inflammasome-related components including NLRP1A, NLRP3, AIM2, gasdermin D, and caspase-1. It also reduced IL-1β and TNF expression during the early phase of disease and increased expression of the anti-apoptotic gene BCL-2. Conclusions: Our findings indicate that CBG modulates distinct components of the inflammatory signaling pathways, and its effects translated into significant improvement in clinical scoring based on swelling, erythema, stiffness in rat CIA model.

Keywords: Cannabinoids, Cannabigerol, Rheumatoid arthritis, CIA model, Inflammasome

Received: 15 Sep 2025; Accepted: 20 Oct 2025.

Copyright: © 2025 Šteigerová, Sklenárová, Bazyuk, Záveský, Jelínek, Arora, Stránský, Kučera, Sepodes, Šoóš, Šíma and Slanar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Martin Šíma, martin.sima@lf1.cuni.cz
Ondrej Slanar, ondrej.slanar@lf1.cuni.cz

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.