Jolkinolide B通过下调核糖体蛋白和干扰蛋白合成抑制分枝杆菌生长

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2025-06-26 DOI:10.1016/j.bmc.2025.118294

Renxiang Zhao , Xiuyan Han , Changming Chen , Shujing Zhang , Yuzhuo Wu , Chao Wang , Xiaochi Ma

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引用次数: 0

摘要

中药大戟（Euphorbia fischeriana Steud）长期用于治疗淋巴结结核（TB）。本研究表明，鱼氏双歧杆菌（E. fischeriana）成分Jolkinolide B对M. tuberculosis H37Ra具有抑菌活性，最低抑菌浓度（MIC）为3 μg/mL。此外，在2 × MIC浓度下，对感染M. tuberculosis的RAW264.7巨噬细胞有杀菌作用。通过转录组的机制研究发现，Jolkinolide B显著降低了17种核糖体蛋白的转录，从而抑制了结核分枝杆菌的蛋白质合成。RT-qPCR证实Jolkinolide B以浓度依赖的方式降低分枝杆菌核糖体蛋白的表达。形态学观察表明，Jolkinolide B使结核杆菌变短、变形。本研究发现了一种来自鱼芽胞杆菌的天然化合物，并阐明了其抗结核作用机制，为合理使用中药和抗生素治疗结核病提供了依据。

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Jolkinolide B inhibits mycobacterial growth by down-regulating ribosomal proteins and interfering with protein synthesis

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Jolkinolide B inhibits mycobacterial growth by down-regulating ribosomal proteins and interfering with protein synthesis

The traditional Chinese medicine Euphorbia fischeriana Steud (E. fischeriana) has been used for treating lymph node tuberculosis (TB) for a long time. This study demonstrates that Jolkinolide B, a component of E. fischeriana, exhibits antimycobacterial activity with a minimum inhibitory concentration (MIC) of 3 μg/mL against M. tuberculosis H37Ra. Additionally, it shows bactericidal effect on RAW264.7 macrophages infected with M. tuberculosis at a concentration of 2 × MIC. Mechanistic study via transcriptome revealed that Jolkinolide B significantly reduced the transcription of 17 ribosomal proteins, thereby inhibiting protein synthesis in M. tuberculosis. RT-qPCR confirmed that Jolkinolide B decreased the expression of mycobacterial ribosomal proteins in a concentration-dependent manner. Finally, morphological observations indicated that Jolkinolide B caused the tubercle bacilli to become shorter and deformed. This study highlights a natural compound from E. fischeriana and clarifies its mechanism of action against TB, supporting the rational use of traditional Chinese medicine (TCM) and antibiotics in TB treatment.

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.