Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
J Ethnopharmacol. 2011 Jun 1;135(3):662-71. doi: 10.1016/j.jep.2011.03.070. Epub 2011 Apr 8.
Salvianolic acid (SAL) and tanshinone (TAN) are major hydrophilic and lipophilic compounds, respectively, from one herbal medicine, Danshen, which has been widely and successfully used for treating cardiovascular diseases in Asian countries. Because few studies have reported different molecular mechanisms between the different compounds in same herb, we investigate if separate molecular pathways are involved in cardioprotective effect by different active components of Danshen.
We used an acute myocardial infarction (MI) model to compare the cardioprotective effects of SAL and TAN in rats. Both infarct size and echocardiographic response were evaluated at 3, 7, 14 and 28 days after surgery. Genes involved in ischemic injury and in responses to SAL or TAN treatment in ischemic hearts were identified by microarray analysis and verified by quantitative real-time RT-PCR.
Results showed that both SAL and TAN delay the development of ischemia by decreasing infarct size and improving systolic function post MI. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated different kinetics and gene expression profiles by SAL and TAN. SAL acts in a later period after ischemia, and its effect is probably mediated by downregulation of genes involved in oxidative stress, certain G-protein coupled receptor activities and apoptosis. On the other hand, TAN acts relatively early after ischemic injury and its effect is at least in part mediated by inhibition of intracellular calcium, cell adhesion and alternative complement pathway. Strikingly, we found that TAN, a recently identified member of selective estrogen receptor modifier (SERM), indeed regulates genes known to be involved in estrogen metabolism post MI.
Although both SAL and TAN contribute to the cardioprotective effect of Danshen, there are significant mechanistic and temporal differences between the two: TAN acts at an early stage after ischemic injury mainly by inhibition of intracellular calcium and cell adhesion pathways whereas SAL acts mainly by down-regulating apoptosis.
丹酚酸（SAL）和丹参酮（TAN）分别是一种草药丹参中的主要亲水性和脂溶性化合物，在亚洲国家被广泛成功地用于治疗心血管疾病。由于很少有研究报道同一草药中不同化合物之间的不同分子机制，我们研究了不同的丹参活性成分是否通过不同的分子途径参与心脏保护作用。
我们使用急性心肌梗死（MI）模型比较了 SAL 和 TAN 在大鼠中的心脏保护作用。在手术后 3、7、14 和 28 天评估梗死面积和超声心动图反应。通过微阵列分析鉴定与缺血损伤和丹参酮或 TAN 治疗缺血心脏反应相关的基因，并通过定量实时 RT-PCR 验证。
结果表明，SAL 和 TAN 通过减少梗死面积和改善 MI 后收缩功能来延迟缺血的发展。基因本体论和京都基因与基因组百科全书（KEGG）途径分析表明，SAL 和 TAN 的动力学和基因表达谱不同。SAL 在缺血后晚期起作用，其作用可能是通过下调涉及氧化应激、某些 G 蛋白偶联受体活性和细胞凋亡的基因来介导的。另一方面，TAN 在缺血损伤后相对早期起作用，其作用至少部分是通过抑制细胞内钙、细胞黏附和替代补体途径来介导的。值得注意的是，我们发现，TAN，一种最近被鉴定为选择性雌激素受体调节剂（SERM）的成员，确实调节了 MI 后已知参与雌激素代谢的基因。
尽管 SAL 和 TAN 都有助于丹参的心脏保护作用，但两者之间存在显著的机制和时间差异：TAN 在缺血损伤后早期起作用，主要通过抑制细胞内钙和细胞黏附途径，而 SAL 主要通过下调细胞凋亡起作用。
