甘草次酸联合抗结核药对结核杆菌活性研究

研究选取中药单体18β-甘草次酸联合一线抗结核药物异烟肼(INH)、利福平(RFP)和链霉素(SM)，利用MABA法检测其体外单独及联合作用于牛源结核分枝杆菌的抗菌活性。18β-甘草次酸单独作用于结核分枝杆菌标准株(ATCC 27294)和牛分枝杆菌标准株（ATCC 19210）的最低抑菌浓度（MIC）分别为50和100 μg/mL。临床分离的2株敏感株和6株耐药株的MIC值分别为25～50和100～200 μg/mL。18β-甘草次酸联合INH、RFP和SM作用于6株耐药株均具有协同作用，且MIC值明显下降，INH的MIC值下降2～32倍（FICIs 0.125～0.375），RFP的MIC值下降4～8倍（FICIs 0.240～0.490），SM的MIC值下降4～16倍（FICIs 0.165～0.460）。中药单体药物对正常细胞BHK-21具有较低的细胞毒性，对肝癌细胞SMMC具有较好抑制作用。结果表明,18β-甘草次酸与抗结核药物INH、RFP和SM联合使用对结核分枝杆菌具有较好的抗菌药理活性。

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.