Funakoshi-Tago Megumi, Okamoto Kazuhi, Izumi Rika, Tago Kenji, Yanagisawa Ken, Narukawa Yuji, Kiuchi Fumiyuki, Kasahara Tadashi, Tamura Hiroomi
Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Int Immunopharmacol. 2015 Mar;25(1):189-98. doi: 10.1016/j.intimp.2015.01.012. Epub 2015 Jan 19.
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.
蜂胶已被用于民间医学以改善健康状况并预防炎症性疾病；然而，展现其抗炎活性的成分仍不为人知。我们在此研究了从尼泊尔蜂胶中分离出的黄酮类化合物对白细胞介素-33（IL-33）信号通路的影响，以阐明其中涉及的抗炎机制。从尼泊尔蜂胶中分离出的8种黄酮类化合物中，3',4'-二羟基-4-甲氧基黄檀酮、4-甲氧基黄檀酮、cearoine和白杨素这4种化合物显著抑制了IL-33诱导的骨髓来源肥大细胞（BMMC）中包括白细胞介素-6（IL-6）、肿瘤坏死因子α（TNFα）和白细胞介素-13（IL-13）在内的炎症基因的mRNA表达。这4种黄酮类化合物还抑制了IL-33诱导的核因子κB（NF-κB）的激活，这与其对细胞因子表达的抑制作用一致。这些黄酮类化合物的作用归因于对IL-33诱导的IKK激活的抑制，IKK激活会导致IκBα的降解和NF-κB的核定位。另一方面，从尼泊尔蜂胶中分离出的其他黄酮类化合物，如异甘草素、阔苞菊素、7-羟基黄烷酮和(+)-紫穗槐二氢黄酮醇，对IL-33信号通路或细胞因子表达没有影响。因此，这些结果表明3',4'-二羟基-4-甲氧基黄檀酮、4-甲氧基黄檀酮、cearoine和白杨素是尼泊尔蜂胶抗炎活性的活性成分。
