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

Megumi Funakoshi-Tago, Kazuhi Okamoto, Rika Izumi, Kenji Tago, Ken Yanagisawa, Yuji Narukawa, Fumiyuki Kiuchi, Tadashi Kasahara, Hiroomi Tamura

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39 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)189-198
Number of pages10
JournalInternational Immunopharmacology
Issue number1
Publication statusPublished - 2015 Mar



  • Anti-inflammatory activity
  • Flavonoid
  • IKK
  • IL-33
  • NF-kB
  • Propolis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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