Department of ICT Environmental Health System, Graduate School, SoonChunHyang University, Asan-si, Chungnam, South Korea.
Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Asan-si, Chungnam, South Korea.
Arch Pharm (Weinheim). 2022 Mar;355(3):e2100404. doi: 10.1002/ardp.202100404. Epub 2021 Dec 29.
Toll-like receptors (TLRs) are integral membrane-bound receptors that are central to innate and adaptive immune responses. They are known to activate a cascade of downstream signals to induce the secretion of inflammatory cytokines, chemokines, and type I interferons. Dysregulated activation of TLR signaling pathways can induce the activation of various transcription factors, such as nuclear factor kappa B (NF-κB) and interferon regulatory factor 3 (IRF3). TLRs act via MyD88- and TRIF-mediated pathways to induce inflammatory responses. To evaluate the therapeutic potential of isobavachalcone (IBC), a natural chalcone component of Angelica keiskei, we examined its effects on signal transduction via TLR signaling pathways. IBC inhibited the activation of NF-κB and IRF3 induced by TLR agonists and their target genes. IBC also inhibited the activation of NF-κB and IRF3 induced by overexpression of downstream signaling components of TLR signaling pathways. These results suggest that IBC can regulate both MyD88- and TRIF-dependent signaling pathways of TLRs, resulting in a dramatic increase of new therapeutic options for various inflammatory diseases involving TLRs.
Toll 样受体 (TLRs) 是一种整合膜结合受体，是先天和适应性免疫反应的核心。它们已知能激活下游信号级联反应，诱导炎症细胞因子、趋化因子和 I 型干扰素的分泌。TLR 信号通路的失调激活可诱导各种转录因子的激活，如核因子 kappa B (NF-κB) 和干扰素调节因子 3 (IRF3)。TLRs 通过 MyD88 和 TRIF 介导的途径激活炎症反应。为了评估异甘草素（IBC）作为当归中天然查尔酮成分的治疗潜力，我们研究了其对 TLR 信号通路信号转导的影响。IBC 抑制 TLR 激动剂及其靶基因诱导的 NF-κB 和 IRF3 的激活。IBC 还抑制 TLR 信号通路下游信号转导成分过表达诱导的 NF-κB 和 IRF3 的激活。这些结果表明，IBC 可以调节 TLR 的 MyD88 和 TRIF 依赖性信号通路，为涉及 TLR 的各种炎症性疾病提供了新的治疗选择。
