A novel antioxidant, octyl caffeate, suppression of LPS/IFN-γ-induced inducible nitric oxide synthase gene expression in rat aortic smooth muscle cells

George Hsiao, Ming Yi Shen, Wen Chiung Chang, Yu Wen Cheng, Shiow Lin Pan, Yueh Hsiung Kuo, Tzeng Fu Chen, Joen Rong Sheu

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23 Citations (Scopus)

Abstract

In the present study, we investigated the effects and mechanisms of a novel potent antioxidant, octyl caffeate, on the induction of iNOS expression by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) in cultured primary rat aortic smooth muscle cells (RASMCs) in vitro and LPS-induced hypotension in vivo. Octyl caffeate (0.1-1.0μM) exerted a concentration-dependent inhibition of iron-catalyzed lipid peroxidation in rat brain homogenates. Furthermore, octyl caffeate (20, 50, and 100μM) concentration-dependently diminished the initial rate of superoxide-induced NBT reduction and the enzymatic activity of xanthine oxidase. It also concentration-dependently (1-50μM) inhibited the NO production, iNOS protein and messenger RNA expressions upon stimulation by LPS (100μg/mL)/IFN-γ (100U/mL) in RASMCs. In addition, we found that octyl caffeate did not significantly affect IκBα degradation stimulated by LPS/IFN-γ in RASMCs. On the other hand, octyl caffeate (10 and 50μM) significantly suppressed activation of c-Jun-N-terminal kinase and extracellular signal-regulated kinase. Moreover, octyl caffeate (10mg/kg, i.v.) significantly inhibited the fall in mean arterial pressure stimulated by LPS (7.5mg/kg) in rats. In conclusion, we demonstrate that a novel potent antioxidant, octyl caffeate, significantly ameliorates circulatory failure of endotoxemia in vivo by a mechanism involving suppression of iNOS expression through inactivation of mitogen-activated protein kinases in RASMCs.

Original languageEnglish
Pages (from-to)1383-1392
Number of pages10
JournalBiochemical Pharmacology
Volume65
Issue number8
DOIs
Publication statusPublished - Apr 15 2003

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Keywords

  • Antioxidant
  • Endotoxic shock
  • iNOS
  • LPS/IFN-γ
  • MAPK
  • Octyl caffeate

ASJC Scopus subject areas

  • Pharmacology

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