title: A polyphenolic flavonoid glabridin: Oxidative stress response in multidrug-resistant Staphylococcus aureus.
abstract: 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.
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Vigyasa
authors.initials: V
authors.lastname: Singh
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Pal
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India. Electronic address: mpdarokar@yahoo.com.
authors.forename: Mahendra P
authors.initials: MP
authors.lastname: Darokar
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry; D005419:Flavonoids / Q000008:administration & dosage / Q000737:chemistry; D006035:Glycyrrhiza / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007529:Isoflavones / Q000008:administration & dosage* / Q000737:chemistry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000008:administration & dosage* / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D059808:Polyphenols / Q000008:administration & dosage; D017382:Reactive Oxygen Species / Q000378:metabolism; D014640:Vancomycin / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D005419:Flavonoids; D007529:Isoflavones; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D014640:Vancomycin; D006861:Hydrogen Peroxide; C107601:glabridin
keywords: Antioxidant; Glabridin; Oxidative stress; Reactive oxygen species; S. aureus