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(-)-Licarin A 对 BALB/c 小鼠的抗结核活性和亚急性毒性:一种从关木通中分离得到的新木脂素。

Antitubercular activity and the subacute toxicity of (-)-Licarin A in BALB/c mice: a neolignan isolated from Aristolochia taliscana.

机构信息

Unidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI (CMN-SXXI), Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.

出版信息

Arch Med Res. 2013 Feb;44(2):99-104. doi: 10.1016/j.arcmed.2012.12.006. Epub 2013 Jan 4.

DOI:10.1016/j.arcmed.2012.12.006
PMID:23291382
Abstract

BACKGROUND AND AIMS

Tuberculosis remains a worldwide health problem and requires long-term treatment with several antibiotics; therefore, compliance problems and the emergence of multidrug resistance (MDR) are involved. (-)-Licarin A (LA) was isolated from diverse plants such as Aristolochia taliscana and possesses antimycobacterial, antiinflammatory, trypanocidal, and neuroprotective activities. The aim of the study was to determine the antitubercular and subacute toxicity of LA isolated from A. taliscana in BALB/c mice.

METHODS

The antitubercular activity of LA was tested in a TB murine model inducing disease with M. tuberculosis H37Rv or MDR. Mice were treated with LA (5 mg/kg) for 30 and 60 days; post/treatment, lung bacilli loads and pneumonia percentage were determined. The subacute toxicity of LA (21 days) was evaluated in healthy mice. After treatment, biochemical and hematological parameters were determined and main organs were analyzed histologically.

RESULTS

In animals infected with drug-sensitive or MDR strains, LA produced a significant decrease of pulmonary bacillary burdens at day 30 of treatment, and a significant pneumonia reduction at days 30 and 60 of treatment. Regarding subacute toxicity, LA administration during 21 days showed no abnormalities in main-organ macro- and microarchitecture. Biochemical and hematological parameters analyzed showed no statistical differences between control and treated groups.

CONCLUSIONS

(-)-Licarin A reduces pneumonia of mice infected with both mycobacterium strains. Also, subacute toxicity of LA exhibits no major signs of damage. Biochemical and hematological parameters and histological analyses indicate that LA caused no significant changes at the doses assayed.

摘要

背景与目的

结核病仍然是一个全球性的健康问题,需要长期使用多种抗生素进行治疗;因此,涉及到了依从性问题和多药耐药(MDR)的出现。(-)-Licarin A(LA)从不同的植物中分离出来,如马兜铃属植物,具有抗分枝杆菌、抗炎、杀锥虫和神经保护活性。本研究的目的是确定从马兜铃属植物中分离出的 LA 对 BALB/c 小鼠的抗结核和亚急性毒性。

方法

在结核小鼠模型中,用结核分枝杆菌 H37Rv 或 MDR 诱导疾病,测试 LA 的抗结核活性。用 LA(5mg/kg)治疗小鼠 30 和 60 天;治疗后,测定肺内细菌负荷和肺炎百分比。在健康小鼠中评估 LA 的亚急性毒性(21 天)。治疗后,测定生化和血液学参数,并对主要器官进行组织学分析。

结果

在感染敏感或 MDR 株的动物中,LA 在治疗第 30 天显著降低肺内细菌负荷,在治疗第 30 和 60 天显著降低肺炎。关于亚急性毒性,LA 在 21 天的给药期间,主要器官的宏观和微观结构没有异常。分析的生化和血液学参数显示,对照组和治疗组之间没有统计学差异。

结论

(-)-Licarin A 可减轻感染两种分枝杆菌菌株的小鼠的肺炎。此外,LA 的亚急性毒性没有明显的损伤迹象。生化和血液学参数以及组织学分析表明,在检测的剂量下,LA 没有引起明显的变化。

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