In vitro and in vivo anti-inflammatory effects of a novel 4,6-bis ((E)-4-hydroxy-3-methoxystyryl)-1-phenethylpyrimidine-2(1 H)-thione

Jong Hun Lee, Kyeong Ryoon Lee, Zheng Yuan Su, Sarandeep S.S. Boyanapalli, Dipti N. Barman, Mou Tuan Huang, Lin Chen, Sadgopan Magesh, Longqin Hu, Ah Ng Tony Kong

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Inflammation plays a critical defensive role in the human body. However, uncontrolled or aberrant inflammatory responses contribute to various acute and chronic diseases. The Nrf2-ARE pathway plays a pivotal role in the regulation of inflammatory markers, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). On the basis of this concept, we synthesized a novel anti-inflammatory 4,6-bis ((E)-4-hydroxy-3-methoxystyryl)-1-phenethylpyrimidine- 2(1H)-thione (HPT), and in vitro experiments using HepG2-C8 ARE-luciferase- transfected cells demonstrated the induction of Nrf2-ARE activity. In lipopolysaccharide (LPS)-induced RAW 264.7 cells, HPT treatment reduced the production of nitric oxide (NO) as well as the protein and mRNA expression levels of COX-2 and iNOS, in a dose-dependent manner. In addition, HPT suppressed the mRNA expression of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. In LPS-induced macrophages, HPT inhibited COX-2 and iNOS by blocking the activation of p38 and c-Jun NH2-terminal kinase (JNK) but not extracellular signal-regulated kinase (ERK1/2). Furthermore, an in vivo anti-inflammatory study was performed using a TPA-induced skin inflammation mouse model, and the results showed that HPT reduced TPA-induced inflammation and attenuated the expression of COX-2 and iNOS in TPA-induced mouse skin tissue. Thus, HPT demonstrated anti-inflammatory activity both in LPS-induced RAW 264.7 cells and TPA-stimulated mouse skin and may therefore serve as a potential anti-inflammatory agent.

Original languageEnglish (US)
Pages (from-to)34-41
Number of pages8
JournalChemical Research in Toxicology
Issue number1
StatePublished - Jan 21 2014

All Science Journal Classification (ASJC) codes

  • Toxicology

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