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.

Sauchinone, a lignan isolated from Saururus chinenesis, is known to exhibit anti-inflammatory and anti-oxidant effects. Recently, sauchinone has been reported to inhibit the growth of various cancer cells, but its effects on breast cancer cells remain poorly understood. In this study, we investigated the effects of sauchinone on the growth of breast cancer cells along with the underlying molecular mechanisms. Our results show that sauchinone treatment markedly inhibited the proliferation, migration, and invasion of breast cancer cells. Sauchinone reduced the phosphorylation of Akt, ERK, and CREB increased by transforming growth factor-β. In particular, sauchinone treatment suppressed the expression of matrix metalloproteinase-13 (MMP13) by regulating the Akt-CREB signaling pathway. Sauchinone was less effective in inhibiting cell migration in Mmp13-knockdown cells than in control cells, suggesting that MMP13 may be a novel target for sauchinone. Our study suggests that sauchinone inhibits the growth of breast cancer cells by attenuating the Akt-CREB-MMP13 pathway. In addition, the targeted inhibition of MMP13 by sauchinone represents a promising approach for the treatment of breast cancer.

Toll‐like receptors (TLRs) can recognize specific signatures of invading microbial pathogens and activate a cascade of downstream signals to induce the secretion of inflammatory cytokines, chemokines, and type I interferons. The activation of TLRs triggers two downstream signaling pathways: the MyD88‐ and the TRIF‐dependent pathways. To evaluate the therapeutic potential of epoxomicin, a member of the linear peptide αʹ,βʹ‐epoxyketone first isolated from an actinomycetes strain, we examined its effects on signal transduction via TLR signaling pathways. Epoxomicin inhibited the activation of NF‐kB and IRF3 induced by TLR agonists, decreased the expression of interferon‐inducible protein‐10, and inhibited the activation of NF‐kB and IRF3 induced by overexpression of downstream signaling components of TLR signaling pathways. These results suggest that epoxomicin can regulate both the MyD88‐ and TRIF‐dependent signaling pathways of TLRs. Thus, it might have potential as a new therapeutic drug for a variety of inflammatory diseases.