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Xanthohumol from Humulus lupulus L. potentiates the killing of Mycobacterium tuberculosis and mitigates liver toxicity by the combination of isoniazid in mouse tuberculosis models
RSC Advances ( IF 3.9 ) Pub Date : 2020-4-1 , DOI: 10.1039/c9ra10347c
Hai Lou 1, 2 , Fen Zhang 3 , Liqin Lu 3 , Yingying Ding 4 , Xiaohui Hao 1, 2
Affiliation  

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.

中文翻译:

来自 Humulus lupulus L. 的黄腐酚通过在小鼠结核病模型中联合异烟肼增强结核分枝杆菌的杀灭作用并减轻肝毒性

抗结核药物引起的肝毒性是结核病患者的主要问题。黄腐酚是啤酒花中的主要异戊二烯基查尔酮,具有多种生物活性,包括抗菌和保肝活性。本研究旨在探讨黄腐酚与异烟肼联合防治结核分枝杆菌的作用。- 感染小鼠。通过每天用异烟肼治疗8周诱导肝损伤。实验过程中,未感染组和正常对照组给予等体积生理盐水,黄腐酚组仅给予等体积黄腐酚,异烟肼组仅给予等体积异烟肼。联合治疗组不仅接受了异烟肼,还接受了相应的黄腐酚。实验结果表明,与其他组相比,异烟肼联合黄腐酚导致肺和脾脏集落形成单位计数最低。此外,其他积极结果表明异烟肼联合黄腐酚明显减轻抗结核药物引起的肝损伤,表现为 ALT、AST、ALP、胆红素和 MDA 水平下降和 SOD 水平升高,GSH-Px 和 ATP 酶。对保肝活性机制的研究表明,黄腐酚能够激活抗氧化防御系统并保护肝细胞膜。异烟肼与黄腐酚合用,具有更有效的抑菌保肝作用。结核分枝杆菌感染的小鼠多于单独使用异烟肼。总之,黄腐酚有可能成为结核病治疗的有效佐剂。
更新日期:2020-04-01
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