Isolation and identification of antimicrobial multicyclic terpenoids from the medicinal plant <i>Salvia officinalis</i> and development of a formulation against clinical <i>Staphylococcus aureus</i> strains

Staphylococcus aureus, particularly multi-drug resistant strains, presents significant challenges in dairy farming due to its role in causing bovine mastitis, which leads to substantial economic losses and limited treatment options. Seeking alternative therapies, we investigated the potential of a topical formulation derived from the medicinal herb Salvia officinalis to combat S. aureus growth and biofilms associated with bovine mastitis. Through systematic extraction in different solvents and fractionation by column chromatography, we isolated and identified three key multicyclic terpenoids-ferruginol, sugiol, and sclareol-exhibiting significant antimicrobial activity. The formulation effectively inhibited biofilm formation, with minimum inhibitory concentration (MIC) values ranging from 0.09 to 0.74 mg ml-1 against clinical S. aureus strains, comparable to or lower than those of the pure compounds. Moreover, it displayed robust anti-adhesive properties, reducing biofilm formation by 20%-79% at subinhibitory concentrations. Furthermore, the formulation successfully disrupted pre-existing biofilms, achieving reductions ranging from 30% to 82%. Cytotoxicity assays confirmed the safety of the formulation on mammary epithelial cells, with cell viability maintained at 100% at MIC. Our findings underscore the therapeutic potential of Sa. officinalis-derived compounds in managing bovine mastitis caused by S. aureus, emphasizing their antimicrobial efficacy and safety profile.