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Jolkinolide B inhibits mycobacterial growth by down-regulating ribosomal proteins and interfering with protein
Renxiang Zhao1, Xiuyan Han2, Changming Chen3
1College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, People's Republic of China; The Second Affiliated Hospital of Dalian Medical University, Dalian 116044, People's Republic of China.
Abstract:
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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