Caffeic acid inhibits acute hyperhomocysteinemia-induced leukocyte rolling and adhesion in mouse cerebral venules

Hai-Ping Zhao1, Juan Feng, Kai Sun

  • 1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.

Microcirculation (New York, N.Y. : 1994)
|December 8, 2011
PubMed

Insights

Curcumin (CA) effectively reduces leukocyte rolling and adhesion in the brain during hyperhomocysteinemia (HHcy). This action is linked to decreased inflammation and suppressed signaling pathways in leukocytes.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Hyperhomocysteinemia (HHcy) is associated with increased leukocyte adhesion in cerebral venules, contributing to neuroinflammation.
  • Leukocyte adhesion plays a critical role in the pathogenesis of cerebrovascular diseases.

Purpose of the Study:

  • To investigate the therapeutic effects of curcumin (CA) on HHcy-induced leukocyte rolling and adhesion in mouse cerebral venules.
  • To elucidate the underlying mechanisms of CA's action, including its impact on inflammatory mediators and signaling pathways.

Main Methods:

  • Intravital microscopy was used to assess leukocyte rolling and adhesion in mouse cerebral venules following DL-homocysteine (DL-Hcy) and CA administration.
  • Flow cytometry and immunohistochemistry were employed to evaluate reactive oxygen species (ROS) production, adhesion molecule expression, and signaling pathway activation (Src/PI3K/Akt).

Main Results:

  • CA significantly inhibited HHcy-induced leukocyte rolling and adhesion in cerebral venules.
  • CA reduced ROS production, pro-inflammatory cytokines (KC, MIP-2, MCP-1), and the expression of adhesion molecules (E-selectin, ICAM-1) on endothelium and leukocytes.
  • CA suppressed CD18 phosphorylation and the Src/PI3K/Akt signaling pathway in leukocytes.

Conclusions:

  • Curcumin demonstrates a protective effect against HHcy-induced leukocyte adhesion in cerebral venules.
  • The anti-adhesive effects of CA are mediated by the downregulation of adhesion molecule expression and the suppression of the Src/PI3K/Akt pathway in leukocytes.
Abstract

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