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评价亚麻酸和共轭亚油酸作为有效抑制剂对结核分枝杆菌的抗结核活性。

Evaluation of anti-tubercular activity of linolenic acid and conjugated-linoleic acid as effective inhibitors against Mycobacterium tuberculosis.

机构信息

Department of Biomedical Science, Kyung Hee University School of Medicine, 26 Kyunghee-daero, Dongdaemun-gu, Seoul 130-701, Republic of Korea; Department of Medical Zoology, Kyung Hee University School of Medicine, 26 Kyunghee-daero, Dongdaemun-gu, Seoul 130-701, Republic of Korea.

出版信息

Asian Pac J Trop Med. 2016 Feb;9(2):125-9. doi: 10.1016/j.apjtm.2016.01.021. Epub 2016 Jan 11.

Abstract

OBJECTIVE

To evaluate a new pharmacological activity/effect of linolenic acid (α- and γ-form) and conjugated-linoleic acid (CLA) causing antibacterial activity against Mycobacterium tuberculosis (Mtb).

METHODS

The anti-Mtb activity/effect of linolenic acid and CLA were determined using different anti-Mtb indicator methods such as resazurin microtiter assay (REMA) and MGIT 960 system assay. The Mtb was incubated with various concentrations (12.5-200 μg/mL) of the compounds and anti-Mtb first-line drugs for 5 d in the REMA, and for 3 wk in MGIT 960 system assay.

RESULTS

Linolenic acid and CLA obviously indicated their anti-Mtb activity/effect by strongly inhibiting the growth/proliferation of Mtb in a dose-dependent manner in the REMA and the MGIT 960 system assay. Interestingly, linolenic acid and CLA consistently induced anti-Mtb activity/effect by effectively inhibiting the growth/proliferation of Mtb in MGIT 960 system for 21 d with a single treatment, and their minimum inhibitory concentrations were measured as 200 μg/mL respectively.

CONCLUSIONS

These results demonstrate that linolenic acid and CLA not only have effective anti-Mtb activity/properties, but also induce the selective-anti-Mtb effects by strongly inhibiting and blocking the growth/proliferation of Mtb through a new pharmacological activity/action. Therefore, this study provides novel perspectives for the effective use of them and the potential that can be used as potent anti-Mtb candidate drugs, as well as suggests the advantage of reducing the cost and/or time for developing a new/substantive drug by effectively repurposing the existing drugs or compounds as one of new strategies for the global challenge of tuberculosis.

摘要

目的

评估亚麻酸(α-和γ-形式)和共轭亚油酸(CLA)的新药理活性/作用,其具有抗分枝杆菌(Mtb)的抗菌活性。

方法

使用不同的抗 Mtb 指示剂方法(如 Resazurin 微量滴定法(REMA)和 MGIT 960 系统检测法)来确定亚麻酸和 CLA 的抗 Mtb 活性/作用。将 Mtb 与不同浓度(12.5-200μg/ml)的化合物和抗 Mtb 的一线药物在 REMA 中孵育 5 天,在 MGIT 960 系统中孵育 3 周。

结果

亚麻酸和 CLA 在 REMA 和 MGIT 960 系统中均以剂量依赖性方式强烈抑制 Mtb 的生长/增殖,明显表现出抗 Mtb 活性/作用。有趣的是,亚麻酸和 CLA 连续地以单一治疗方式在 MGIT 960 系统中有效地抑制 Mtb 的生长/增殖,诱导出抗 Mtb 活性/作用,其最小抑菌浓度分别为 200μg/ml。

结论

这些结果表明,亚麻酸和 CLA 不仅具有有效的抗 Mtb 活性/特性,而且通过强烈抑制和阻断 Mtb 的生长/增殖,产生选择性的抗 Mtb 作用,通过一种新的药理活性/作用。因此,本研究为有效利用亚麻酸和 CLA 提供了新的视角,以及作为有潜力的抗 Mtb 候选药物的可能性,并提示了通过有效重新利用现有药物或化合物作为新策略之一,为全球结核病挑战提供了降低开发新药物/实质性药物的成本和/或时间的优势。

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