Anti-inflammatory activity of flavonoids in Nepalese propolis is attributed to inhibition of the IL-33 signaling pathway

• Published in: International immunopharmacology 2015-03, Vol.25 (1), p.189-198
• Main Authors: Funakoshi-Tago, Megumi, Okamoto, Kazuhi, Izumi, Rika, Tago, Kenji, Yanagisawa, Ken, Narukawa, Yuji, Kiuchi, Fumiyuki, Kasahara, Tadashi, Tamura, Hiroomi
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory activity; Anti-Inflammatory Agents - administration & dosage; Bone Marrow Cells - drug effects; Bone Marrow Cells - immunology; Cells, Cultured; Cytokines - genetics; Cytokines - metabolism; Flavonoid; Flavonoids - administration & dosage; Gene Expression Regulation - drug effects; IKK; IL-33; Inflammation Mediators - metabolism; Interleukin-33 - immunology; Mast Cells - drug effects; Mast Cells - immunology; Mice; NF-kappa B - metabolism; NF-κB; Propolis; Propolis - administration & dosage; Propolis - immunology; Signal Transduction - drug effects; Transcriptional Activation - drug effects
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2015.01.012

Propolis has been used in folk medicine to improve health and prevent inflammatory diseases; however, the components that exhibit its anti-inflammatory activity remain unknown. We herein investigated the effects of flavonoids isolated from Nepalese propolis on the IL-33 signaling pathway to clarify the anti-inflammatory mechanism involved. Of the 8 types of flavonoids isolated from Nepalese propolis, 4 types of compounds, such as 3′,4′-dihydroxy-4-methoxydalbergione, 4-methoxydalbergion, cearoin, and chrysin, markedly inhibited the IL-33-induced mRNA expression of inflammatory genes including IL-6, TNFα and IL-13 in bone marrow-derived mast cells (BMMC). These four flavonoids also inhibited the IL-33-induced activation of nuclear factor κB (NF-κB), which was consistent with their inhibitory effects on cytokine expression. The effects of these flavonoids are attributed to inhibition of IL-33-induced activation of IKK, which leads to the degradation of IκBα and nuclear localization of NF-κB. On the other hand, other flavonoids isolated from Nepalese propolis, such as isoliquiritigenin, plathymenin, 7-hydroxyflavanone, and (+)-medicarpin, had no effect on the IL-33 signaling pathway or cytokine expression. Therefore, these results indicate that 3′,4′-dihydroxy-4-methoxydalbergione, 4-methoxydalbergion, cearoin, and chrysin are the substances responsible for the anti-inflammatory activity of Nepalese propolis. [Display omitted] •Flavonoids in propolis reduce the IL-33-induced mRNA expression of IL-6 and IL-13.•Flavonoids in propolis inhibit the IL-33-induced activation of NF-κB.•Flavonoids in propolis inhibit the IL-33-induced activation of IKK.