title: Antimycobacterial and synergistic effects of 18β-glycyrrhetinic acid or glycyrrhetinic acid-30-piperazine in combination with isoniazid, rifampicin or streptomycin against Mycobacterium bovis.
abstract: 18ß-Glycyrrhetinic acid (18ßGA) is a major bioactive component of liquorice with known activity. In this study, we found that both 18ßGA and its derivative glycyrrhetinic acid-30-piperazine (PGA), have potent antimycobacterial properties against the drug-susceptible and drug-resistant Mycobacterium bovis. More importantly, they exhibited synergistic effects with the first-line drugs isoniazid (INH), rifampicin (RIF) and streptomycin (SM) against clinical M. bovis isolates, including drug-resistant strains. In combination with a subinhibitory concentration of 18ßGA, the minimum inhibitory concentrations (MICs) of the anti-tuberculosis agents decreased, ranging from 4- to 16-, 4- to 8- and 4- to 8-fold for INH (fractional inhibitory concentration index (FICI) 0.125-0.375), RIF (FICI 0.118-0.281) and SM (FICI 0.094-0.275), respectively. In the presence of PGA, MICs for the first-line agents resulted in a 4-16-fold decrease for INH (FICI 0.094-0.266, RIF (FICI 0.114-0.313) and SM (FICI 0.094-0.281). Additionally, the MICs of 18ßGA or PGA alone showed significant decreases ranging from 8- to 16-, 8- to 64- and 8- to 128-fold in the presence of INH, RIF and SM, respectively. These findings indicate that 18ßGA and its derivatives might serve as potential therapeutic compounds for future antimycobacterial drug development.
authors.affiliation: College of Life Science, Ningxia University, Yinchuan, Ningxia 750021, China.
authors.forename: Xuezhang
authors.initials: X
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.forename: Xueqiang
authors.initials: X
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Jia
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yujiong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007538:Isoniazid / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009163:Mycobacterium bovis / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D010879:Piperazines; C119129:18alpha-glycyrrhetinic acid; D006034:Glycyrrhetinic Acid; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin