Salvia willeana (Holmboe) Hedge extract as a natural dual-action agent: anti-inflammatory and antimicrobial synergy

Abstract

Salvia comprises valuable species are rich in phenolic compounds and possess medicinal activities. Salvia willeana (Holmboe) Hedge is known as Troodos sage, endemic to Cyprus and has strong antiseptic activity. This study investigates the potential synergistic anti-inflammatory effects of S. willeana extract combined with non-steroidal anti-inflammatory agents and evaluates the extract’s enhancement of antimicrobial activity of selected antibiotics against Methicillin-resistant Staphylococcus aureus (MRSA). The phenolic compounds of methanol extract from S. willeana were investigated by means of LC-MS/MS. Anti-inflammatory activity of the extract (30–300 µg/mL) was evaluated alone and in combination with diclofenac sodium through the protein denaturation inhibition assay. The antimicrobial activity of S. willeana extract against MRSA (ATCC 33591) was investigated using microdilution assay. A checkerboard assay was performed to evaluate the combinatory effect of the extract in combination with different antibiotics against MRSA. For statistical analysis, one-way ANOVA, post hoc Tukey’s multiple comparisons test and chi-square test were used. Twenty-two phenolic compounds in S. willeana methanol extract were detected and rosmarinic acid and jaceosidin were found as the major compounds. The total phenolic and flavonoid contents were calculated as 314.98 ± 11.67 mg GAE/g and 156.30 ± 7.39 mg QE/g dry extract, respectively. S. willeana methanol extract showed concentration-dependent anti-inflammatory activity. Furthermore, the extract has a lower IC 50 (109.4 µg/mL) relative to standard diclofenac sodium (434.0 µg/mL). The combination of S. willeana extract and diclofenac sodium showed a synergistic interaction since the experimental IC 50 (Z exp = 14.90 µg/mL) was lower than the theoretical (Z add = 271.7 µg/mL). MIC and MBC of S. willeana extract against MRSA were determined as 125 µg/mL. The combination of β-lactam (ampicillin, cefazolin) and aminoglycoside (kanamycin, streptomycin) antibiotics with the extract resulted in synergistic interactions (FICI < 0.5) whereas, the combination of chloramphenicol with the extract showed an indifferent effect (FICI = 2.0). The dual anti-inflammatory and antimicrobial activity of S. willeana extract highlight its potential for the treatment of inflammatory bacterial infections.