Dao-Tan decoction inhibits tumor necrosis factor-α-induced intercellular adhesion molecule-1 expression by blocking JNK and p38 signaling pathways in human umbilical vein endothelial cells

Pharm Biol. 2012 Sep;50(9):1111-7. doi: 10.3109/13880209.2012.658476. Epub 2012 Jul 4.

Abstract

Context: Dao-Tan decoction (DTD) is a Chinese herb prescription used to treat atherosclerosis or dizziness for centuries. Previous study shows that DTD could inhibit intercellular adhesion molecule-1 (ICAM-1) expression induced by tumor necrosis factor-α (TNF-α). However, its mechanism has never been clearly described.

Objective: To examine the hypothesis that DTD might inhibit TNF-α-induced ICAM-1 expression through regulating the mitogen-activated protein kinase (MAPK) pathways, involving Jun N-terminal kinase (JNK) and p38.

Materials and methods: The rats were orally administrated with DTD for 3 days (2.3 g/kg per day), then the serum was collected. Human umbilical vein endothelial cells (HUVECs) were cultured and stimulated by TNF-α with or without DTD serum. The expression of ICAM-1 mRNA was examined by reverse transcription-polymerase chain reaction and the expression of p38 and JNK was examined by Western blot analysis.

Results: DTD serum significantly inhibits TNF-α-induced ICAM-1 expression by 17-41% on HUVECs. TNF-α-induced JNK and p38 activations, which were involved in ICAM-1 expression, were significantly inhibited with DTD serum treatment by 10-50% on HUVEC.

Discussion and conclusion: Based on the theory of traditional Chinese medicine (TCM), pathogenesis of atherosclerosis is caused by "blood" and "phlegm" attached on blood vessels. DTD has a function of "dissolving phlegm", thus it is chosen for the treatment of atherosclerosis. This study demonstrated that DTD could inhibit the expression of ICAM-1, by significantly preventing the activation of JNK and p38, which are important factors of atherosclerosis. Therefore, the present study indicates the pharmacological basis for treatment of atherosclerosis with DTD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / blood
  • Atherosclerosis / drug therapy
  • Atherosclerosis / metabolism
  • Cardiovascular Agents / blood
  • Cardiovascular Agents / pharmacokinetics
  • Cardiovascular Agents / pharmacology*
  • Cells, Cultured
  • Down-Regulation / drug effects*
  • Drugs, Chinese Herbal / analysis
  • Drugs, Chinese Herbal / pharmacokinetics
  • Drugs, Chinese Herbal / pharmacology*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System / drug effects*
  • Male
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Serum / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Cardiovascular Agents
  • Drugs, Chinese Herbal
  • ICAM1 protein, human
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • daotan
  • Intercellular Adhesion Molecule-1
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases