Effects of Citral on Lipopolysaccharide-Induced Inflammation in Human Umbilical Vein Endothelial Cells

Inflammation. 2016 Apr;39(2):663-71. doi: 10.1007/s10753-015-0292-0.

Abstract

Citral is an active compound of lemongrass oil which has been reported to have anti-inflammatory effects. In this study, we investigated the effects of citral on lipopolysaccharide (LPS)-induced inflammatory response in a rat model of peritonitis and human umbilical vein endothelial cells (HUVECs). LPS was intraperitoneally injected into rats to establish a peritonitis model. The HUVECs were treated with citral for 12 h before exposure to LPS. The levels of TNF-α and IL-8 were measured using ELISA. Western blotting was used to detect the expression of VCAM-1, ICAM-1, NF-κB, and PPAR-γ. The results showed that citral had a protective effect against LPS-induced peritonitis. Citral decreased the levels of WBCs and inflammatory cytokines TNF-α and IL-6. Citral also inhibited LPS-induced myeloperoxidase (MPO) activity in the peritoneal tissue. Treatment of HUVECs with citral significantly inhibited TNF-α and IL-8 expression induced by LPS. LPS-induced VCAM-1 and ICAM-1 expression were also suppressed by citral. Meanwhile, we found that citral inhibited LPS-induced NF-κB activation in HUVECs. Furthermore, we found that citral activated PPAR-γ and the anti-inflammatory effects of citral can be reversed by PPAR-γ antagonist GW9662. In conclusion, citral inhibits LPS-induced inflammatory response via activating PPAR-γ which attenuates NF-κB activation and inflammatory mediator production.

Keywords: NF-κB; PPAR-γ; citral; human umbilical vein endothelial cells; peritonitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclic Monoterpenes
  • Anilides / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Adhesion / drug effects
  • Enzyme Activation / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Inflammation / drug therapy
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Leukocyte Count
  • Lipopolysaccharides
  • Monoterpenes / pharmacology*
  • NF-kappa B / metabolism*
  • Neutrophils / immunology
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / metabolism*
  • Peritonitis / drug therapy*
  • Peritonitis / pathology
  • Peroxidase / metabolism
  • Plant Oils / chemistry
  • Plant Oils / pharmacology
  • Rats
  • Terpenes / chemistry
  • Terpenes / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • 2-chloro-5-nitrobenzanilide
  • Acyclic Monoterpenes
  • Anilides
  • Anti-Inflammatory Agents
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • Monoterpenes
  • NF-kappa B
  • PPAR gamma
  • Plant Oils
  • Terpenes
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • lemongrass oil
  • Peroxidase
  • citral