title: 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.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Chinese Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors: Xiaobo
authors: X
authors: Huang
authors: Fen
authors: F
authors: Wang
authors: Wenqiang
authors: W
authors: Chen
authors: Zongxin
authors: Z
authors: Li
authors: Ningqun
authors: N
authors: Wang
authors: Yujing
authors: Y
authors: Chen
authors: Kristine
authors: K
authors: von Maltzan
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D002317:Cardiovascular Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D002317:Cardiovascular Agents; D004365:Drugs, Chinese Herbal; C573420:ICAM1 protein, human; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C528579:daotan; D018799:Intercellular Adhesion Molecule-1; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases