Antimicrobial and Anti-Inflammatory Caffeic Acid Improves Killing by Macrophages

Objectives: The role of Streptococcus mutans in dental caries etiology is well established and the control of their concentration in oral cavity by antimicrobial agents is an alternative approach to avoid tooth decay. Caffeic acid is a phenolic compound found in medicinal plants which presents anti-oxidant, antimicrobial and anti-inflammatory effects. The purpose of this study was to investigate the antimicrobial effects of caffeic acid against Streptococcus mutans, its anti-inflammatory effects in macrophage RAW 264.7 stimulated with Streptococcus mutans and the influence of caffeic acid on the killing of Streptococcus mutans by macrophages. Methods: Streptococcus mutans (10⁸ ufc / ml) were plated with brain heart infusion medium and incubated with caffeic acid to determinate the half maximal inhibitory concentration (IC₅₀) of the drug by means of a microtiter assay. Macrophage cells (5 × 10⁴ cells / well) were incubated with caffeic acid to determinate cell viability and toxicity by MTT assay and anti-inflammatory effects were measured by nitrite and TNF-alpha accumulation in the media. The effect of caffeic acid on Streptococcus mutans survival following internalization by macrophages was investigated. Data were analyzed using one way ANOVA followed by Tukey test (alpha= 0.05). Results: Caffeic acid presented antimicrobial activity against Streptococcus mutans (IC₅₀ = 0.5035 ± 0.024 mg / ml) while did not exert toxic effect in macrophages, even at high concentration of the drug. 100 µM of caffeic acid reduced about 50% of nitrite and TNF-alpha accumulation in macrophages stimulated with Streptococcus mutans, compared to cells stimulated with Streptococcus mutans without caffeic acid (p<0.05), indicating an anti-inflammatory effect. Although nitrite and TNF-alpha expression was reduced, 100 and 50 µM of caffeic acid improved killing of Streptococcus mutans by macrophages. Conclusion: Caffeic acid presented antimicrobial activity against Streptococcus mutans and anti-inflammatory effects in macrophages, without affect killing. Financial support: FAPESP and CNPq.