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去甲二氢愈创木酸(NDGA)和α-山竹黄酮通过诱导自噬抑制结核分枝杆菌的生长。

Nordihydroguaiaretic acid (NDGA) and α-mangostin inhibit the growth of Mycobacterium tuberculosis by inducing autophagy.

作者信息

Guzmán-Beltrán Silvia, Rubio-Badillo Miguel Ángel, Juárez Esmeralda, Hernández-Sánchez Fernando, Torres Martha

机构信息

Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, México City, Mexico.

Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, México City, Mexico.

出版信息

Int Immunopharmacol. 2016 Feb;31:149-57. doi: 10.1016/j.intimp.2015.12.027. Epub 2015 Dec 29.

DOI:10.1016/j.intimp.2015.12.027
PMID:26735610
Abstract

Tuberculosis (TB) remains as a global health problem. The prevalence of this infection is related to the association with other diseases, such as HIV, neglect treatment and misuse of antibiotics. Hence, the identification of new drugs is required to eradicate TB. Possible alternatives to existing antibiotics include pure compounds extracted from medicinal plants, which are an important source of antimicrobial agents. The aim of this study was to evaluate the effect of nordihydroguaiaretic acid (NDGA) and α-mangostin on Mycobacterium tuberculosis growth and bacterial survival in infected macrophages derived from the human THP-1 cell line and monocytes. Our results show that both compounds directly inhibit M. tuberculosis growth in liquid medium with Minimal Inhibitory Concentrations (MIC) of 250 and 62 μg/mL respectively, likely through preventing bacterial replication. In addition, NDGA and α-mangostin were able to induce autophagy in human cells at lower concentrations (7 and 6 μg/mL, respectively) and contributed to the elimination of intracellular bacteria. NDGA and α-mangostin could be candidates for coadjuvant therapy in cases of drug-resistant TB, and their ability to enhance the immune response by promoting autophagy might contribute to TB treatment.

摘要

结核病(TB)仍然是一个全球性的健康问题。这种感染的流行与其他疾病(如艾滋病毒)、忽视治疗以及抗生素的滥用有关。因此,需要鉴定新的药物来根除结核病。现有抗生素的可能替代物包括从药用植物中提取的纯化合物,这些植物是抗菌剂的重要来源。本研究的目的是评估去甲二氢愈创木酸(NDGA)和α-山竹黄酮对结核分枝杆菌生长以及在源自人THP-1细胞系和单核细胞的感染巨噬细胞中细菌存活的影响。我们的结果表明,这两种化合物均能在液体培养基中直接抑制结核分枝杆菌的生长,最低抑菌浓度(MIC)分别为250和62μg/mL,可能是通过阻止细菌复制来实现的。此外,NDGA和α-山竹黄酮能够在较低浓度(分别为7和6μg/mL)下诱导人细胞自噬,并有助于消除细胞内细菌。NDGA和α-山竹黄酮可能是耐多药结核病辅助治疗的候选药物,它们通过促进自噬增强免疫反应的能力可能有助于结核病的治疗。

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