Synergistic Effect of the Mucosa-Friendly Agents Berberine and Tea Tree Oil on Mucosal Protection Against Neisseria gonorrhoeae in an In Vitro T84 Cell Mucosa Model.

Introduction:Neisseria gonorrhoeae, a bacterium responsible for gonorrhea, can spread through oral sex, causing pharyngeal gonorrhea, which is also a leading cause of urethritis in outpatient clinics. This study investigated whether tea tree oil (TTO) alone or in combination with other natural products could serve as an effective alternative to chlorhexidine in preventing the spread of oral gonorrhea. Methods: An in vitro model was developed using T84 epithelial cells as a mucosal layer and Neisseria gonorrhoeae strain MS11. The study assessed the minimal inhibitory concentration (MIC), bacterial adherence, invasion, and transmigration across the mucosal barrier. Berberine (BB), a major and bioactive alkaloid derived from Coptis chinensis, was tested with and without TTO in MIC assays and epithelial cell viability tests. Ceftriaxone was used as a positive control. Results: The MIC values for TTO, BB, and ceftriaxone against the MS11 strain were determined to be 0.2%, 5 μg/mL, and 0.0125 μg/mL, respectively. Notably, the combination of TTO with BB demonstrated a synergistic effect, reducing the MIC to 0.000625% TTO + 1.25 μg/mL BB. This combination provided the strongest protective effect. No cytotoxicity was observed in the epithelial cell viability tests for 0.2% diluted TTO, 5 μg/mL BB, or the combination of 0.000625% TTO + 1.25 μg/mL BB. Conclusions: BB, when combined with TTO, exhibited a synergistic antimicrobial effect against Neisseria gonorrhoeae strain MS11 in the T84 mucosal model. These findings highlight the potential of this combination as a natural alternative to chlorhexidine gluconate for managing oral gonorrhea.