Background: Rheumatoid arthritis (RA) belongs to the chronic autoimmune diseases. Despite undeniable progress, current therapeutic options for this disease are not entirely satisfactory. Therefore, searching for new drugs represents the therapeutic challenge. Non-psychoactive derivatives of Cannabis sativa , which previously show some in-vitro anti-inflammatory properties, but have not yet been tested in vivo , seem to be a promising option.

Objectives: Therefore, the aim of this work was to evaluate the anti-inflammatory effects of cannabigerol (CBG) in a rat model of RA.

Methods: A total of 32 female Wistar rats were randomized into 4 groups: placebo (PCB), CBG, glucocorticosteroids (GC), and negative control. In the PCB, GC, and CBG groups, the collagen-induced arthritis (CIA) was induced. CBG group was treated orally with 2 ml of a substance containing 30 mg CBG once daily. GC group were treated with 1ml of a substance containing 0.15mg methylprednisolone once daily. The PCB was treated with the same volume of saline. Rats in the negative control group were treated with saline. Treatment lasted 29 days in all groups. The effect of tested substances was assessed by clinical scoring and the gene expression of selected inflammatory markers from the serum. On day 29, the rats were euthanized and their hind limbs were amputated. The TNF-alpha, STAT 3, and caspase 3 expression levels were monitored by reverse transcription polymerase chain reaction (RT-PCR).

Results: At the end of experiment, we observed statistically lower clinical scores (expressed as mean±SD) in the GC group (4.44±4.64, P= 0.0093) and the GBG group (7.36±0.94, P= 0.0397) in comparison to the PCB (11.25±4.40). We also noticed a slower onset of RA symptoms at the beginning of the experiment in the CBG and the GC group in comparison to the PCB. Gene expression levels of TNF-alpha was significantly reduced in the GC group and showed trend toward reduction in the CBG group in comparison to the PCB group. Gene expression of STAT 3 was significantly reduced in both GC and CBG groups comparing with the PCB group. Gene expression of caspase 3 was significantly reduced in the CBG group vs the PCB group, while in the GC group, the expression level was surprisingly not reduced.

Conclusion: Generally, we observed better clinical scores and reduced gene expression levels of pro-inflammatory cytokines in the GBG and CG groups in comparison with the PCB. Therefore, CBG has emerged as a potentially beneficial substance in the treatment of RA.

REFERENCES: NIL.

Acknowledgements: This work was supported by AZV grant No. AZV NU22-08-00346 and by the Charles University project Cooperatio (research area PHAR). Michaela Sklenárová wishes to acknowledge the support provided by the Pharmaceutical Applied Research Centre (the PARC) for her scientific work.

Disclosure of Interests: None declared.