The effect of dihydropyrazines on lipopolysaccharide-stimulated human hepatoma hepg2 cells via regulating the TLR4-myd88-mediated NF-κb signaling pathway

Madoka Esaki, Takumi Ishida, Yuu Miyauchi, Shinji Takechi

Research output: Contribution to journalArticlepeer-review

Abstract

Dihydropyrazines (DHPs), including 3-hydro-2,2,5,6-tetramethylpyrazine (DHP-3), are glycation products that are spontaneously generated in vivo and ingested via food. DHPs generate various radicals and reactive oxygen species (ROS), which can induce the expression of several antioxidant genes in HepG2 cells. However, detailed information on DHP-response pathways remains elusive. To address this issue, we investigated the effects of DHP-3 on the nuclear factor-κB (NF-κB) pathway, a ROS-sensi-tive signaling pathway. In lipopolysaccharide-stimulated (LPS-stimulated) HepG2 cells, DHP-3 decreased phosphorylation levels of inhibitor of NF-κB (IκB) and NF-κB p65, and nuclear translocation of NF-κB p65. In addition, DHP-3 reduced the expression of Toll-like receptor 4 (TLR4) and the adaptor protein myeloid differentiation primary response gene 88 (MyD88). Moreover, DHP-3 suppressed the mRNA expression of tumor necrosis factor-alpha (TNFα), and interleukin-1 beta (IL-1β). Taken together, these results suggest that DHP-3 acts as a negative regulator of the TLR4-MyD88-mediated NF-κB signaling pathway.

Original languageEnglish
Pages (from-to)401-409
Number of pages9
JournalJournal of Toxicological Sciences
Volume45
Issue number7
DOIs
Publication statusPublished - 2020

All Science Journal Classification (ASJC) codes

  • Toxicology

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