Eupatorium makinoi suppresses toll-like receptor signaling pathways

Toll-like receptors (TLRs) recognize microbial molecules that are widely presented by pathogens and initiate the innate immune system. TLR signaling is divided into two different signaling pathways, the myeloid differential factor 88 (MyD88)- and Toll/interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF)-dependent pathways. Eupatorium makinoi, a plant species in Asteraceae, is used for medicinal purposes in China, Korea, and Japan. Through our previous research, we found that an ethanol extract of E. makinoi (EEM) suppresses inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. In this study, we investigated the effect of EEM on TLRs signaling pathways. EEM suppresses NF-κB activation and iNOS and COX-2 expressions induced by TLR2 or TLR4 agonists. Also, EEM suppresses the activation of interferon (IFNs) regulatory factor 3 (IRF3) induced by TLR3 or TLR4 agonists. All results indicate that EEM suppresses myeloid differentiation primary-response protein 88 (MyD88) and TRIF-dependent signaling pathways of TLRs and the expressions of target genes derived from the activation of TLRs