Potent Anti-staphylococcal Metabolites in Salvia miltiorrhiza

Development of novel agents to treat infections caused by multidrug-resistant bacteria is an urgent priority. Medicinal plants are a recognised source of diverse bioactive compounds with capacities to tackle such organisms [ 1 ]. The root of Salvia miltiorrhiza Bunge (red sage or Danshen, Lamiaceae) has been used traditionally to treat coronary heart diseases, although S.miltiorrhiza extracts have also been shown to possess antimicrobial activities against a range of pathogenic organisms [ 2 ], [ 3 ]. The aim of this study was to investigate metabolites from S.miltiorrhiza previously uncharacterised in terms of antimicrobial activities and potential to negate efflux-mediated resistance in Staphylococcus aureus. These metabolites were tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone, salvianolic acid A, Miltirone, protocatechuicaldhyde, rosmarinic acid, caffeic acid and danshensu. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentration (MBC) assays were determined against S. aureus ATCC25 923, SA-1199B+NorA (expressing the NorA efflux pump) and XU212+TetK (expressing the TetK efflux pump). Miltirone and dihydrotanshinone had the lowest MIC values; 0.5 – 1 µg/mL. The MBC values of Miltirone for S. aureus ATCC25 923 was 2 µg/mL, for SA-1199B+NorA and XU212+TetK was 4 µg/mL. However, the MBC value for dihydrotanshinone was > 128 µg/mL for all S. aureus strains, indicating bacteriostatic activities. At sub-inhibitory concentrations, both metabolites potentiated the activities of tetracycline and norfloxacin, yielding a 2- or 4-fold reduction in MICs against S.aureus XU212+TetK and SA-1199B+NorA, respectively. The MIC of the other metabolites ranged between 512 – 64 µg/mL. Overall, evaluation of these compounds indicates that they could be drug leads in managing staphylococcal infections. Publication History Article published online: 12 December 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany