Department of Medical Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam, Republic of Korea.
Phytochemistry. 2010 Oct;71(14-15):1736-40. doi: 10.1016/j.phytochem.2010.07.008. Epub 2010 Aug 9.
Toll-like receptors (TLRs) play important inductive roles in innate immune responses for host defense against invading microbial pathogens. Activation of TLR4 by lipopolysaccharide (LPS) induces dimerization of TLR4 and, subsequently, activation of downstream signaling pathways including nuclear factor-kappa B and interferon regulatory factor 3. TLR4 dimerization may be an early regulatory event in activating signaling pathways induced by LPS. Here, biochemical evidence is reported that isoliquiritigenin, one of the major ingredients derived from licorice root, inhibits LPS-induced TLR4 dimerization resulting in inhibition of nuclear factor-kappa B and interferon regulatory factor 3 activation, and cyclooxygenase-2 and inducible nitric oxide synthase expression. These results suggest that isoliquiritigenin modulates TLR-mediated signaling pathways at the receptor level. Furthermore, these results suggest that TLRs themselves may be important targets for the prevention of chronic inflammatory diseases.
Toll 样受体 (TLRs) 在宿主防御入侵微生物病原体的先天免疫反应中发挥重要的诱导作用。脂多糖 (LPS) 通过激活 TLR4 诱导 TLR4 二聚化,随后激活包括核因子-κB 和干扰素调节因子 3 在内的下游信号通路。TLR4 二聚化可能是 LPS 诱导的信号通路激活的早期调节事件。在这里,报告了生化证据表明,甘草根的主要成分之一异甘草素抑制 LPS 诱导的 TLR4 二聚化,从而抑制核因子-κB 和干扰素调节因子 3 的激活以及环加氧酶-2 和诱导型一氧化氮合酶的表达。这些结果表明,异甘草素在受体水平上调节 TLR 介导的信号通路。此外,这些结果表明 TLR 本身可能是预防慢性炎症性疾病的重要靶点。