Hydroxy-Safflower Yellow A inhibits the TNFR1-Mediated Classical NF-κB Pathway by Inducing Shedding of TNFR1

Haifang Wang, Jinlian Liu, Yuejin Yang, Qingwen Cao, Xueping Huo, Shuhui Ma, Jun Hu, Fredrick M. Pavalko, Qinshe Liu

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Hydroxy-safflower yellow A (HSYA) is the major active component of safflower, a traditional Asia herbal medicine well known for its cardiovascular protective activities. The purpose of this study was to investigate the effect of HSYA on TNF-α-induced inflammatory responses in arterial endothelial cells (AECs) and to explore the mechanisms involved. The results showed that HSYA suppressed the up-regulation of ICAM-1 expression in TNF-α-stimulated AECs in a dose-dependent manner. High concentration (120 μM) HSYA significantly inhibited the TNF-α-induced adhesion of RAW264.7 cells to AECs. HSYA blocked the TNFR1-mediated phosphorylation and degradation of IκBα and also prevented the nuclear translocation of NF-κB p65. Moreover, HSYA reduced the cell surface level of TNFR1 and increased the content of sTNFR1 in the culture media. TNF-α processing inhibitor-0 (TAPI-0) prevented the HSYA inhibition of TNFR1-induced IκBα degradation, implying the occurrence of TNFR1 shedding. Furthermore, HSYA induced phosphorylation of TNF-α converting enzyme (TACE) at threonine 735, which is thought to be required for its activation. Conclusively, HSYA suppressed TNF-α-induced inflammatory responses in AECs, at least in part by inhibiting the TNFR1-mediated classical NF-κB pathway. TACE-mediated TNFR1 shedding can be involved in this effect. Our study provides new evidence for the antiinflammatory and anti-atherosclerotic effects of HSYA.

Original languageEnglish (US)
Pages (from-to)790-796
Number of pages7
JournalPhytotherapy Research
Volume30
Issue number5
DOIs
StatePublished - May 1 2016

Keywords

  • NF-κB pathway
  • TNF-α
  • TNF-α converting enzyme
  • TNFR1
  • arterial endothelial cell
  • hydroxy-safflower yellow A

ASJC Scopus subject areas

  • Pharmacology

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