Centella asiatica (L.) Urban Leaf Extracts Inhibit the Growth of Bacterial Triggers of Selected Autoimmune Inflammatory Diseases and Potentiate the Activity of Conventional Antibiotics

Introduction: An increase in antibiotic resistance and a corresponding decrease in antimicrobial discovery have directed researchers towards alternative therapies, including plant based medicines. However, synergistic combinations of plant extracts with conventional antibiotics may be a far more effective approach in overcoming resistance and potentiating the activity of antibiotics that are otherwise ineffective against resistant bacterial strains. Methods: The antibacterial activity of Centella asiatica (Gotu Kola) extracts was investigated by disc diffusion and quantified by liquid dilution and solid phase MIC assays. The extracts were also combined with a range of conventional antibiotics and tested against various microbial triggers of autoimmune diseases. The ΣFIC values obtained from these assays were used to determine the class of combinational effects and isobologram analysis was used to determine the ideal synergistic ratio(s). Toxicity was evaluated by Artemia nauplii mortality assays. Results: The methanolic extracts showed good inhibitory activity against several microbial triggers of autoimmune inflammatory diseases, whilst the chloroform and hexane extracts were also potent inhibitors of K. pneumoniae growth. Combinations of the C. asiatica extracts with conventional antibiotics were often substantially more effective in inhibiting bacterial growth. One synergistic and 10 additive interactions were noted. Notably, the methanolic extract restored significant growth inhibitory activity to chloramphenicol and tetracycline when tested in combination against K. pneumoniae. In contrast, two antagonistic interactions were noted for combinations containing gentamycin (against A. baylyi and S. pyogenes), indicating that those combinations should be avoided when treating infections caused by those bacteria. Conclusion: C. asiatica extracts have potential as inhibitors of bacterial triggers of selected autoimmune inflammatory diseases. Furthermore, extract components may also potentiate the activity of two antibiotics that are relatively ineffective alone. Isolation of these agents may be beneficial in drug design against several bacteria, including the microbial triggers of rheumatoid arthritis, ankylosing spondylitis and multiple sclerosis.

Key words: Ankylosing spondylitis, Conventional antimicrobials, Drug combinations, Interaction, Medicinal plants, Multiple sclerosis, Rheumatoid arthritis, Synergy.