| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Outline of Final Research Achievements |
Toll-like receptors (TLRs) have been implicated in the pathogenesis of chronic inflammatory diseases. In this study, based on an extensive screening of vegetable extracts for TLR-inhibiting activity, we found cabbage extracts to be the richest sources of a TLR signaling inhibitor. We performed activity-guiding separation of the principal inhibitors and identified iberin from the cabbage. In addition, it was revealed that iberin specifically acted on the dimerization step of TLRs in the TLR signaling pathway. Moreover, we developed a novel probe combining an isothiocyanate-reactive group and an alkyne functionality for click chemistry and detected the probe bound to the TLRs in living cells, suggesting that iberin disrupts dimerization of the TLRs via covalent binding. These findings establish the TLR dimerization step as a target of food-derived anti-inflammatory compounds.
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