Isobavachalcone suppresses the TRIF-dependent signaling pathway of Toll-like receptors.

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.

Anti-inflammatory effects of Gingerenone A through modulation of toll-like receptor signaling pathways.

Toll-like receptors (TLRs) play a pivotal role in initiating immune responses, particularly in the context of inflammation. However, an excessive inflammation can detrimentally affect the immune homeostasis Thus, it is important to regulate TLR signaling pathways appropriately. Gingerenone A (GIA), a bioactive compound derived from ginger, has garnered significant attention due to its potential anti-inflammatory properties. In this study, we investigate modulatory effects of GIA on TLR signaling pathways. Results showed that GIA effectively suppressed TLR-mediated inflammatory responses by modulating key signaling molecules such as nuclear factor kappa B and interferon regulatory factor 3. These results indicate that GIA is a novel regulator of TLR signaling, offering promising avenues for the development of new anti-inflammatory agents.