| dc.description.abstract | Streptococcal pharyngitis, caused by Streptococcus pyogenes, is a significant health issue worldwide. Beta-lactam antibiotics and non-steroidal anti-inflammatory drugs are recommended for treatment and pain management. This research stems from the global interest in identifying phytochemicals as novel antimicrobials, anti-inflammatory, and analgesic agents for overcoming therapeutic challenges. In this study, carvacrol (5-isopropyl-2-methyl phenol), a monoterpenoid phenolic compound, was investigated for anti-streptococcal, anti-biofilm, and anti-inflammatory activities. The mechanisms of action of these activities were investigated using in vitro models of bacterial cells, human tonsil epithelial cells, and isolated cell membranes. Carvacrol showed significant inhibition of growth and biofilm formation by S. pyogenes. It also could eradicate preformed S. pyogenes biofilms in a concentration- and time-dependent manner. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum biofilm inhibitory concentration (MBIC) of carvacrol against S. pyogenes were 125 µg/mL, 250 µg/mL, and 125 µg/mL, respectively. In addition, Carvacrol exhibited instantaneous bactericidal activity against S. pyogenes. Carvacrol appeared to target the streptococcal cell membrane, and carvacrol treatment altered the membrane fluidity, polarization, permeability, and phospholipid composition. As a result, carvacrol treatment led to cytoplasmic content leakages, such as lactate dehydrogenase and nucleic acids. The hydrophobic carvacrol primarily interacted with acyl chains of bacterial membrane phosphatidylglycerol, phosphatidylethanolamine, and cardiolipins. Carvacrol also inhibited cell surface hydrophobicity, acidity, and downregulated genes (speB, srtB, luxS, covS, dltA, ciaH, and hasA) involved in biofilm formation. In addition, carvacrol possessed anti-inflammatory activities in cultured human tonsil epithelial cells by suppressing the production of pro-inflammatory cytokines such as interleukin-8, interleukin-6, granulocyte chemotactic protein-2, and epithelial-derived neutrophil-activating protein, and other inflammatory biomarkers (human β defensin-2, cyclooxygenase-2, and prostaglandin E2). Therefore, the above results collectively suggest that carvacrol has the potential to be used as a safe and efficacious natural agent in the management of streptococcal pharyngitis. | en_US |
