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

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.