天然产物研究与开发 ›› 2017, Vol. 29 ›› Issue (5): 796-799.doi: 10.16333/j.1001-6880.2017.5.013

• 研究简报 • 上一篇    下一篇

独山瓜馥木促进休眠型结核杆菌复苏的成分和作用机制初探

杨再昌*,邓伟,宋善敏,韩立芬   

  1. 贵州大学药学院,贵阳 550025
  • 出版日期:2017-05-31 发布日期:2017-06-09

Isolation of Component with Resuscitating Activity on Dormant Mycobacterium Tuberculosis from Fissistigma Cavaleriei and Investigation on its Mechanism

YANG Zai-chang*,DENG Wei,SONG Shan-min,HAN Li-fen   

  1. School of Pharmacy,Guizhou University,Guiyang 550025,China
  • Online:2017-05-31 Published:2017-06-09

摘要: 采用活性跟踪分离方法,从独山瓜馥木分离得到能促进休眠型结核杆菌复苏的化合物1,鉴定为β-谷甾醇-9,12-十六碳二烯酸酯。化合物1在浓度为16 μg/mL时开始显示促复苏活性,呈明显的量效关系。异烟肼、乙胺丁醇、利福平和吡嗪酰胺单独用药时,不能杀死休眠型结核杆菌,化合物1(32 μg/mL)与异烟肼联合用药,培养14、21 d后检测,休眠型结核杆菌被杀死,化合物1可增强利福平对休眠菌的杀灭作用,但分别与乙胺丁醇和吡嗪酰胺联合时,均表现为拮抗作用。化合物1能激活休眠型结核杆菌的KatG酶,使细胞内O2含量升高,导致休眠型结核杆菌复苏。

关键词: 独山瓜馥木, 休眠型结核杆菌, 复苏, 作用机制

Abstract: Compound 1,with resuscitating activity on dormant Mycobacterium tuberculosis, was isolated from Fissistigmacavaleriei root by bioassay-guided method. It was identified as β-sitosterol-9,12-hexadecadienoate by physical and spectroscopic methods. Compound 1 showed activity to resuscitate dormant Mycobacterium tuberculosis into active state in a dose-dependent manner with minimum effective concentration of 16 μg/mL.Dormant M.tuberculosis was insensitive to isoniazid,ethambutol,rifamicin and pyrazinamide in single drug. At the concentration of 32 μg/mL,Compound 1 canhelp isoniazid to kill dormant M.tuberculosis after 14 and 21 days of exposure,and increase the killing activity of rifamicin against dormant M.tuberculosis. However,among two-drug combinations,compound 1-ethambutol andcompound 1-pyrazinamide,exhibited antagonistic action on dormant M.tuberculosis. Compound 1 can activate the KatG activity of dormant M. tuberculosis, which caused the content of O2 in dormant M.tuberculosis cells at a high level to trigger the resuscitation of dormant M. tuberculosis.

Key words: FissistigmaCavaleriei, dormant Mycobacterium tuberculosis, resuscitating, mechanism