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

  • Bioorg Med Chem. 2025 Nov 1:129:118294. doi: 10.1016/j.bmc.2025.118294.
Renxiang Zhao  1 ,  Xiuyan Han  2 ,  Changming Chen  3 ,  Shujing Zhang  2 ,  Yuzhuo Wu  2 ,  Chao Wang  4 ,  Xiaochi Ma  5
Affiliations
  • 1. College 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.
  • 2. The Second Affiliated Hospital of Dalian Medical University, Dalian 116044, People's Republic of China.
  • 3. Department of Rheumatology and Immunology, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, People's Republic of China.
  • 4. College of Pharmacy, Dalian Medical University, Dalian 116044, People's Republic of China. Electronic address: [email protected].
  • 5. College 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. Electronic address: [email protected].
PMID: 40616985 DOI: 10.1016/j.bmc.2025.118294
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.

Keywords
Antimycobacterial activity; Euphorbia fischeriana; Jolkinolide B; Mycobacterium tuberculosis; Ribosome.
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