title: Drug Resistance Reversal Potential of Isoliquiritigenin and Liquiritigenin Isolated from Glycyrrhiza glabra Against Methicillin-Resistant Staphylococcus aureus (MRSA).
abstract: Isoliquiritigenin (ISL) and liquiritigenin (LTG) are structurally related flavonoids found in a variety of plants. Discovery of novel antimicrobial combinations for combating methicillin-resistant Staphylococcus aureus (MRSA) infections is of vital importance in the post-antibiotic era. The present study was taken to explore the in vitro and in vivo combination effect of LTG and ISL with β-lactam antibiotics (penicillin, ampicillin and oxacillin) against mec A-containing strains of MRSA. Minimum inhibitory concentration (MIC) of both LTG and ISL exhibited significant anti-MRSA activity (50-100 µg/mL) against clinical isolates of MRSA. The result of in vitro combination study showed that ISL significantly reduced MIC of β-lactam antibiotics up to 16-folds [∑ fractional inhibitory concentration (FIC) 0.312-0.5], while LTG reduced up to 8-folds (∑FIC 0.372-0.5). Time kill kinetics at graded MIC combinations (ISL/LTG + β-lactam) indicated 3.27-9.79-fold and 2.59-3.48-fold reduction in the growth of clinical isolates of S. aureus respectively. In S. aureus-infected Swiss albino mice model, combination of ISL with oxacillin significantly (p < 0.05, p < 0.01, p < 0.001) lowered the systemic microbial burden in blood, liver, kidney, lung and spleen tissues in comparison with ISL, oxacillin alone as well as untreated control. Considering its synergistic antibacterial effect, we suggest both ISL and LTG as promising compounds for the development of novel antistaphylococcal combinations. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Medicinal Plant Chemistry Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow, 226015, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Gaur
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India.
authors.forename: Vivek Kumar
authors.initials: VK
authors.lastname: Gupta
authors.affiliation: Medicinal Plant Chemistry Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow, 226015, India.
authors.forename: Pooja
authors.initials: P
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.
authors.forename: Mahendra Padurang
authors.initials: MP
authors.lastname: Darokar
authors.affiliation: Medicinal Plant Chemistry Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow, 226015, India. bhakunirs2000@gmail.com, rs.bhakuni@cimap.res.in.
authors.forename: Rajendra Singh
authors.initials: RS
authors.lastname: Bhakuni
mesh_terms: D000818:Animals; D047188:Chalcones / Q000378:metabolism*; D004351:Drug Resistance; D004357:Drug Synergism; D044950:Flavanones / Q000378:metabolism*; D006035:Glycyrrhiza / Q000737:chemistry*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice
chemical_list: D047188:Chalcones; D044950:Flavanones; C040920:isoliquiritigenin; C083152:liquiritigenin
keywords: Glycyrrhiza glabra; antibacterial activity; isoliquiritigenin; liquiritigenin; synergism