Department of Chinese Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
Pharm Biol. 2012 Sep;50(9):1111-7. doi: 10.3109/13880209.2012.658476. Epub 2012 Jul 4.
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.
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.
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.
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.
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.
丹参汤（DTD）是一种用于治疗动脉粥样硬化或头晕的中药方剂，已有数百年的历史。先前的研究表明，DTD 可以抑制肿瘤坏死因子-α（TNF-α）诱导的细胞间黏附分子-1（ICAM-1）的表达。然而，其作用机制尚未得到明确描述。
检验丹参汤可能通过调节丝裂原活化蛋白激酶（MAPK）通路，包括 Jun 氨基末端激酶（JNK）和 p38 抑制 TNF-α诱导的 ICAM-1 表达的假说。
大鼠连续 3 天（每天 2.3 g/kg）口服 DTD，收集血清。培养人脐静脉内皮细胞（HUVEC）并用 TNF-α刺激，同时用 DTD 血清处理。采用逆转录-聚合酶链反应检测 ICAM-1mRNA 的表达，Western blot 分析检测 p38 和 JNK 的表达。
DTD 血清可显著抑制 TNF-α诱导的 HUVEC 中 17-41%的 ICAM-1 表达。TNF-α诱导的 JNK 和 p38 激活，参与 ICAM-1 的表达，在 DTD 血清处理后 HUVEC 中被抑制 10-50%。
根据中医理论，动脉粥样硬化的发病机制是由“血”和“痰”在血管上附着引起的。丹参汤具有“化痰”的作用，因此被用于治疗动脉粥样硬化。本研究表明，丹参汤通过显著抑制 JNK 和 p38 的激活，从而抑制 ICAM-1 的表达，这是动脉粥样硬化的重要因素。因此，本研究为丹参汤治疗动脉粥样硬化提供了药理学依据。
