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<p><i>Streptomyces</i> species are prolific producers of structurally diverse secondary metabolites with a broad spectrum of biological activities. In this study, we isolated a novel angucyclinone compound, tsukubacyclinone (<b>1</b>), from the culture broth of <i>Streptomyces</i> sp. K21-0141. Tsukubacyclinone (<b>1</b>) exhibited potent anti-inflammatory effects in vitro. RNA sequencing of TNF-α–stimulated synovial cell line, SW982 revealed that tsukubacyclinone (<b>1</b>) downregulated pro-inflammatory genes, including <i>IL1B</i> and <i>IL6</i>, which was further validated by qPCR, without increasing LDH activity. KEGG pathway analysis indicated modulation of TNF, NF-κB, cytokine–cytokine receptor interaction, and JAK–STAT signaling. ELISA further confirmed a dose-dependent suppression of IL-1β and IL-6 protein. These findings suggest that tsukubacyclinone (<b>1</b>), as a novel angucyclinone-type compound, may target upstream cytokine signaling pathways to attenuate synovial inflammation, highlighting its potential as a disease-modifying agent for osteoarthritis and other chronic joint diseases. Future studies are warranted to investigate its in vivo pharmacological effects and molecular targets.</p>

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Tsukubacyclinone, a novel angucyclinone compound with anti-inflammatory activity in synovial cell line SW982, produced by Streptomyces sp. K21-0141

  • 期刊论文

  • 发表日期：

    2026年7月6日

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  • Fumito Iizuka,
  • Kentaro Uchida,
  • Yuta Kikuchi,
  • Yuta Awano,
  • Miho Nagayoshi,
  • Saki Ikeuchi,
  • Kugo Takeda,
  • Yoshihisa Ohashi,
  • Gen Inoue,
  • Tomoyasu Hirose,
  • Yuki Inahashi

摘要

Streptomyces species are prolific producers of structurally diverse secondary metabolites with a broad spectrum of biological activities. In this study, we isolated a novel angucyclinone compound, tsukubacyclinone (1), from the culture broth of Streptomyces sp. K21-0141. Tsukubacyclinone (1) exhibited potent anti-inflammatory effects in vitro. RNA sequencing of TNF-α–stimulated synovial cell line, SW982 revealed that tsukubacyclinone (1) downregulated pro-inflammatory genes, including IL1B and IL6, which was further validated by qPCR, without increasing LDH activity. KEGG pathway analysis indicated modulation of TNF, NF-κB, cytokine–cytokine receptor interaction, and JAK–STAT signaling. ELISA further confirmed a dose-dependent suppression of IL-1β and IL-6 protein. These findings suggest that tsukubacyclinone (1), as a novel angucyclinone-type compound, may target upstream cytokine signaling pathways to attenuate synovial inflammation, highlighting its potential as a disease-modifying agent for osteoarthritis and other chronic joint diseases. Future studies are warranted to investigate its in vivo pharmacological effects and molecular targets.