Anti-inflammatory Effects of Phytochemicals Having Michael Addition Acceptors by the Modulation of Toll-like Receptor Signaling Pathways
2009
Youn, H.S., Soonchunhyang University, Asan, Republic of Korea
Toll-like receptors (TLRs) play a critical role in the induction of innate immune responses that are essential for host defense against invading microbial pathogens. In general, TLRs have two major downstream signaling pathways, namely MyD88- and TRIF-dependent pathways, leading to the activation of nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) and the expression of inflammatory mediators. TLR4 dimerization is required for the activation of downstream signaling pathways and may be one of the first lines of regulation in activating TLR-mediated signaling pathways. In this paper, the molecular targets of curcumin, 6-shogaol, and cinnamaldehyde in TLR signaling pathways will be discussed. Curcumin, 6-shogaol, and cinnamaldehyde with α,β-unsaturated carbonyl groups inhibit the dimerization of TLR4 induced by lipopolysaccharide, resulting in the downregulation of NF-κB and IRF3. These results suggest that phytochemicals with the structural motif conferring Michael addition inhibit TLR4 dimerization, suggesting a novel mechanism for the anti-inflammatory activity of phytochemicals.
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