Xanthohumol from Humulus lupulus L. potentiates the killing of Mycobacterium tuberculosis and mitigates liver toxicity by the combination of isoniazid in mouse tuberculosis models

Abstract

Anti-tuberculosis drug induced hepatotoxicity is the main problem in tuberculosis patients. Xanthohumol, a major prenyl chalcone present in hops, has diverse biological activities including antibacterial and hepatoprotective activities. The present research aimed to investigate the combined effect of xanthohumol with isoniazid against Mycobacterium tuberculosis-infected mice. The liver damage was induced by treatment with isoniazid daily for 8 weeks. During the experiment, the uninfected group and the normal control group received an equal volume of saline, the xanthohumol group received an equal volume of xanthohumol only, and the isoniazid group received an equal volume of isoniazid only. The combination therapy group received not only isoniazid but also the corresponding xanthohumol. Experimental results showed that isoniazid combined with xanthohumol resulted in the lowest lung and spleen colony-forming unit counts compared to other groups. Furthermore, other positive outcomes implied that isoniazid combined with xanthohumol obviously alleviated anti-tuberculosis drug induced liver damage as indicated by the declined levels of ALT, AST, ALP, bilirubin and MDA and the increased levels of SOD, GSH-Px and ATPases. The study of the mechanisms underlying the hepatoprotective activity showed that xanthohumol was able to activate the antioxidative defense system and protect the hepatocellular membrane. The combination of isoniazid and xanthohumol had more effective bacteriostatic and hepatoprotective activities on Mycobacterium tuberculosis-infected mice than isoniazid alone. In conclusion, xanthohumol has the potential to be an effective adjuvant in tuberculosis treatment.