A polyphenolic flavonoid glabridin: Oxidative stress response in multidrug-resistant Staphylococcus aureus

Glabridin a polyphenolic flavonoid from Glycyrrhiza glabra is known to possess several therapeutic properties. In the present study, we report for the first time the in vitro antibacterial activity (WC values ranging from 3.12 to 25 mu g/mL) of glabridin against multidrug-resistant clinical isolates of S. claret's by inducing oxidative stress. Increased levels of H2O2 and NO were observed in a dose-dependent manner after treatment of glabridin that further affected macromolecules such as DNA, lipids, and proteins. Surprisingly, glabridin was found to possess antioxidant properties when used at lower concentrations using three different methods including DPPH, FRAP, and SOD assays. These observations were further validated through the expression analysis of oxidative stress-responsive genes using qRT-PCR wherein glabridin was observed to up- and down-regulate these genes at lower and higher concentrations, respectively. In in vitro combination experiments, glabriclin was found to reduce the MlC of different antibiotics such as norfloxacin, oxacillin, and vancomycin by up to 4-fold, while the WC of glabridin itself was found to be reduced by up to 8-fold in the presence of antibiotics. A synergistic interaction was observed between norfloxacin and glabriclin when used in combination against multidrug-resistant clinical isolate SA 4627 of Staphylococcus claret's at much lower concentrations, indicating the suitability of glabridin in combination therapy. (C) 2015 Published by Elsevier Inc