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

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.