Could Teas and Refreshing Beverages Based on Sage Help Prevent Gingivitis? An In Silico Molecular Docking Study

Sage (Salvia officinalis L.) has been used for centuries in traditional medicine in Serbia to treat inflammatory conditions of the oral cavity. Gingivitis is a common inflammatory condition primarily associated with bacterial dental plaque, causing redness, swelling, and gingival bleeding. Among bacteria associated with gingival inflammation, Fusobacterium nucleatum has been consistently linked to gingivitis, while Aggregatibacter actinomycetemcomitans has also been implicated.

Molecular docking was employed to investigate the binding affinity of rosmarinic acid and caffeic acid, two important polyphenolic compounds present in aqueous sage extract, to carboxypeptidase from F. nucleatum (PDB ID: 7EP9), whose inactivation could potentially affect peptide utilization and, consequently, the metabolic fitness of F. nucleatum, and de-N-acetilaza from A. actinomycetemcomitans (PDB ID: 4U10), whose inhibition could potentially impair the formation and maintenance of the bacterial biofilm, using chlorhexidine as a conventional oral antiseptic comparator.

The results revealed distinct predicted binding preferences. For 7EP9, caffeic acid showed the most favorable predicted binding potency (ΔG_bind = −6.02 kcal mol⁻¹; Kᵢ = 38.76 µM), followed by rosmarinic acid (ΔG_bind = −5.79 kcal mol⁻¹; Kᵢ = 57.46 µM), whereas chlorhexidine showed unfavorable binding (ΔG_bind = +24.11 kcal mol⁻¹). For 4U10, rosmarinic acid showed the most favorable predicted binding potency (ΔG_bind = −7.65 kcal mol⁻¹; Kᵢ = 2.47 µM), followed by caffeic acid (ΔG_bind = −6.28 kcal mol⁻¹; Kᵢ = 24.89 µM) and chlorhexidine (ΔG_bind = −5.69 kcal mol⁻¹; Kᵢ = 67.02 µM). Complex stabilization involved predominantly conventional hydrogen bonds, together with carbon–hydrogen, π-donor hydrogen bonds, and other π-related interactions.  

The docking results provide a preliminary molecular basis for interactions of caffeic and rosmarinic acids with bacterial proteins, requiring experimental validation. Chlorhexidine showed target-dependent interactions, suggesting potentially different mechanisms of antibacterial action. Based on their long-standing traditional use, sage-based teas and beverages may contribute to oral health and gingivitis prevention.