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.