Isobavachalcone suppresses the TRIF‐dependent signaling pathway of Toll‐like receptors. Issue 3 (29th December 2021)

• Record Type: Journal Article
• Authors: Shin, Seokwon; Park, Jayeon; Lee, Ye Eun; Ko, Hanbin; Youn, Hyung‐Sun
• Is Part Of: Archiv der Pharmazie. Volume 355:Issue 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-29
• Subjects: inflammation -- isobavachalcone -- nuclear factor‐κB -- Toll‐like receptors -- TRIF; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202100404
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: 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. Abstract : To evaluate the therapeutic potential of isobavachalcone (IBC), a natural chalcone component of Angelica keiskei, its effects on Toll‐like receptor (TLR) signal transduction were examined. IBC inhibited the activation of nuclear factor kappa B and interferon regulatory factor 3 induced by TLR agonists and its target genes as well as by overexpression of TLR downstream signaling components. Thus, IBC may regulate both MyD88‐ and TRIF‐dependent TLR signaling, increasing the therapeutic options for inflammatory diseases involving TLRs.