Apigenin inhibits tumor necrosis factor-induced intercellular adhesion molecule-1 upregulation in vivo

Microcirculation. 1996 Sep;3(3):279-86. doi: 10.3109/10739689609148302.


Objective: Apigenin is a flavonoid that effectively blocks intercellular adhesion molecule-1 (ICAM-1) upregulation and leukocyte adhesion in response to cytokines in vitro. In the present study, we characterized the effects of tumor necrosis factor (TNF) on ICAM-1 expression in different tissues of the rat. We then assessed whether apigenin alters this response.

Methods: ICAM-1 expression was measured under baseline conditions or 5 h after treatment with rTNF. We used 125I-labeled anti-rat ICAM-1 monoclonal antibody (mAb) and an isotype-matched control mAb labeled with 131I to correct for nonspecific accumulation of the binding mAb. Animals were pretreated with either placebo, apigenin, narigenin (a flavonoid without inhibitory effect in vitro), or vehicle. Additional groups of animals were treated with either allopurinol, glutathione, dimethyl-thiourea, or an anti-CD18 monoclonal antibody in order to assess possible actions of flavonoids that were mediated via free radical scavenging or through interference with neutrophil function.

Results: Treatment with rTNF resulted in a marked increase in ICAM-1 expression in all organs studied. The magnitude of the response varied in different organs and increases ranged from onefold (lung) to threefold (muscle). Treatment with apigenin blocked ICAM-1 upregulation in organs with low to intermediate responses to rTNF and it significantly attenuated the increased ICAM-1 expression in organs that normally exhibit more marked upregulation. Treatment with narigenin or vehicle did not affect rTNF-induced ICAM-1 upregulation in all tissues studied. Pretreatment with either allopurinol, free radical scavengers, or anti-CD18 monoclonal antibody did not affect the ICAM-1 upregulatory response to rTNF.

Conclusions: TNF-induced ICAM-1 upregulation in vivo effectively is blocked by apigenin through a mechanism that is unrelated to free radical scavenging or leukocyte function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Chamomile
  • Enzyme Inhibitors / pharmacology*
  • Flavanones*
  • Flavonoids / pharmacology*
  • Heart / drug effects
  • Hyaluronoglucosaminidase / antagonists & inhibitors
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Myocardium / metabolism
  • Oils, Volatile / pharmacology*
  • Plants, Medicinal
  • Rats
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Up-Regulation / drug effects*
  • Xanthine Oxidase / antagonists & inhibitors


  • Enzyme Inhibitors
  • Flavanones
  • Flavonoids
  • Oils, Volatile
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Xanthine Oxidase
  • Hyaluronoglucosaminidase
  • naringenin