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 (MIC values ranging from 3.12 to 25 μg/mL) of glabridin against multidrug-resistant clinical isolates...

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Bibliographic Details
Published in:Free radical biology & medicine 2015-10, Vol.87, p.48-57
Main Authors: Singh, Vigyasa, Pal, Anirban, Darokar, Mahendra P.
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - administration & dosage
Antioxidant
Antioxidants - administration & dosage
Antioxidants - chemistry
Flavonoids - administration & dosage
Flavonoids - chemistry
Glabridin
Glycyrrhiza - chemistry
Humans
Hydrogen Peroxide - metabolism
Isoflavones - administration & dosage
Isoflavones - chemistry
Methicillin-Resistant Staphylococcus aureus - drug effects
Methicillin-Resistant Staphylococcus aureus - pathogenicity
Nitric Oxide - metabolism
Oxidative stress
Oxidative Stress - drug effects
Phenols - administration & dosage
Phenols - chemistry
Plant Extracts - administration & dosage
Plant Extracts - chemistry
Polyphenols - administration & dosage
Reactive oxygen species
Reactive Oxygen Species - metabolism
S. aureus
Vancomycin - administration & dosage
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Summary: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 (MIC values ranging from 3.12 to 25 μg/mL) of glabridin against multidrug-resistant clinical isolates of S. aureus 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, glabridin was found to reduce the MIC of different antibiotics such as norfloxacin, oxacillin, and vancomycin by up to 4-fold, while the MIC 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 glabridin when used in combination against multidrug-resistant clinical isolate SA 4627 of Staphylococcus aureus at much lower concentrations, indicating the suitability of glabridin in combination therapy. •Glabridin showed antibacterial activity against MDR clinical isolates of S. aureus.•Glabridin exerts its effect by inducing oxidative stress in a dose-dependent manner.•Glabridin regulates oxidative stress-responsive genes in a dose-dependent manner.•Glabridin also possesses antioxidant properties at lower concentrations.•A synergistic interaction of glabridin with norfloxacin is found when used in combination.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2015.06.016