Synergistic Effects of 18β-glycyrrhetinic Acid in Combination with Antimycobacterial Drugs against Mycobacterium bovis

In this study,we found that 18β-glycyrrhetinic acid had potent antimycobacterial properties against the drug-susceptible and drug-resistant Mycobacterium bovis. Minimum inhibitory concentration （MIC） were 50 and 100 μg/mL after appling 18β-glycyrrhetinic acid alone aginst ATCC 27294 and ATCC 19210; MICs were 25～50 and 100～200 μg/mL after appling 18β-glycyrrhetinic acid alone aginst 2 drug-susceptible and drug-resistant Mycobacterium bovis. More importantly, they exhibited synergistic effects with the first-line drugs isoniazid (INH), rifampicin (RIF) andstreptomycin (SM) against clinical Mycobacterium bovis isolates, including drug-resistant strains. In combination with asubinhibitory concentration of 18β-glycyrrhetinic acid, the minimum inhibitory concentrations (MICs) of the antituberculosisagents decreased, ranging from 2 to 32, 4 to 8 and 4 to 16 fold for INH (fractional inhibitory concentrationindex (FICIs) 0.125～0.375), RIF (FICIs 0.240～0.490) and SM (FICIs 0.165～0.460), 18β-glycyrrhetinic acid had lesser poisonous to BHK-21 cell and could restraint SMMC fission,respectively. These findings indicated that 18β-glycyrrhetinic acid might serve as potential therapeutic compounds for futureantimycobacterial drug development.