基于血清药物化学研究香青兰抗心肌缺血活性部位的活性成分

Anti-myocardial Ischemia Components from Dracocephalum moldavica Extraction Based on Serum Pharmacochemistry Analysis

建立了高效液相色谱法对香青兰抗心肌缺血活性部位进行化学成分指认,共指认了29个化合物。对该活性部位进行初步血清药物化学研究,在给药组血清中共发现20个成分峰,其中12个为代谢产物,8个为原型成分。主要入血原型成分为(+)methyl rabdosiin(1)、(+)rabdosiin(2)、迷迭香酸(5)、田蓟苷(13)、木犀草素-7-O-β-D-葡萄糖醛酸苷(18)、芹菜素-7-O-β-D-葡萄糖醛酸苷(19)、香叶木素-7-O-β-D-葡萄糖醛酸苷(20)和金合欢素-7-O-β-D-葡萄糖醛酸苷(21)。进一步对入血原型成分进行药效研究,发现黄酮类化合物13、18和19体外给予30μg/ml,对二磷酸腺苷(ADP)诱导的大鼠血小板聚集有抑制作用,聚集抑制率分别为8.11%、9.32%和3.27%;酚酸类化合物1、2和5在浓度为12.5μg/ml时,对H_2O_2诱导原代心肌细胞氧化损伤有保护作用,细胞存活率分别为82.79%、84.60%和88.48%。研究表明黄酮类和酚酸类化合物是香青兰抗心肌缺血活性部位中的活性成分。

Here we investigated the anti-myocardial ischemia components from Dracocephalum moldavica extraction（DME）. Twenty-nine phytochemical compounds were primarily pointed out in fingerprints of DME by HPLC. Plasma pharmacochemistry techniques were further employed to screen potential bioactive components in DME. HPLC chromatographic profiles of dosed plasma, blank plasma and DME were acquired, and a total of eight prototype components, including（＋）methyl rabdosiin（1）,（＋）rabdosiin（2）, rosmarinic acid（5）, tilianin（13）, luteolin-7-O-β-D-glucuronide（18）, apigenin-7-O-β-D-glucuronide（19）, diosmetin-7-O-β-D-glucuronide（20）, and acaetin-7-O-β-D-glucuronide（21） were identified by HPLC analysis. These prototype components could be the major bioactive components of DME. Flavone compounds 13, 18, 19, 20 and 21 were tested to inhibit the ADP-induced aggregation of platelets in vitro. The results showed that the platelet aggregation inhibition rate to ADP-induced rat of compounds 13, 18 and 19 were 8.11%, 9.32% and 3.27%, respectively, with a final concentration of 30 μg/ml. Phenolic compounds 1, 2 and 5 were tested to protect the H2O2-induced myocardial cell. The MTT analysis showed that compounds 1, 2 and 5 at 12.5 μg/ml remarkably reduced the cytotoxicity and inhibited cell apoptosis. As a result, the flavone and phenolic compounds of DME may be partially responsible for myocardial ischemia effect.