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

Authors

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

Published in

The Journal of antibiotics. Jul 06, 2026. Epub Jul 06, 2026.

Abstract

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.

PMID:
42410245
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.

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