Jason Batten1, Ian E Cock1,2,*
1School of Environment and Science, Griffith University, Nathan, Queensland, AUSTRALIA.
2Centre for Planetary Health and Food Security, Nathan Campus, Griffith University, Nathan, Queensland, AUSTRALIA.
Background: Apium graveolens L. (commonly known as celery) seeds have been used traditionally to treat a variety of conditions including bacterial infections and inflammation. There is also considerable recent interest in its use as a complementary medicine. However, they are yet to be tested for the ability to inhibit the growth of bacterial triggers of autoimmune diseases. Methods: Antimicrobial activity was assessed using disc diffusion and liquid dilution minimum inhibitory concentration (MIC) assays against a panel of bacterial triggers of some autoimmune diseases. Interactions between the A. graveolens extracts and conventional antibiotics were studied and classified using the sum of the fractional inhibitory concentration (ΣFIC). Notable synergistic interactions were further examined across a range of ratios using isobologram analysis. The toxicity of the individual samples and the combinations was assessed using the Artemia lethality assay (ALA) assay. Results: Apium graveolens seed extracts displayed notable antibacterial activity against the bacterial trigger of rheumatoid arthritis (P. mirabilis), but were ineffective against K. pneumoniae, A. baylyi, P. aeruginosa and S. pyogenes. The ethyl acetate extract was a particularly good inhibitor of P. mirabilis growth, with an MIC of 64μg/mL recorded. The hexane (MIC=256μg/mL) and methanolic extracts (MIC=750μg/mL) also displayed noteworthy inhibitory activity towards P. mirabilis. Furthermore, combining the extracts with conventional antibiotics resulted in significant potentiation of the inhibitory activity for some combinations. Interestingly, all combinations containing the ethyl acetate extract produced either synergistic or additive effects against P. mirabilis. None of the individual components (nor the combinations) were toxic in the ALA assay. Conclusion: The A. graveolens ethyl acetate extract displayed clinically relevant antibacterial activity against P. mirabilis when tested alone, and potentiated the activity of chloramphenicol, gentamicin and ciprofloxacin in combination. Furthermore, the lack of toxicity of the extract and combinations indicates that A. graveolens ethyl acetate extract and antibiotic combinations may provide leads in the development of new therapies to prevent and treat rheumatoid arthritis.
Key words: Medicinal plants, Rheumatoid arthritis, Ankylosing spondylitis, Multiple sclerosis, Conventional antimicrobials, Synergy, Drug interaction, Toxicity.