川芎茎叶中苯酞类化学成分研究

Study on phthalides components from the stems and leaves of Ligusticum chuanxiong

研究川芎Ligusticum chuanxiong茎叶中具有舒张血管活性的苯酞类成分。采用MCI、硅胶等进行成分分离。本文共分离出15个苯酞化合物,分别为当归内酯A(1)、茶芎内酯D(2)、环氧藁本内酯(3)、5-羟基-3-丁烯基苯酞(4)、洋川芎内酯B(5)、7-羟基-3-丁烯基苯酞(6)、Z-藁本内酯(7)、Z-6-羟基-7-甲氧基-藁本内酯(8)、川芎内酯B(9)、欧当归内酯A(10)、东当归内酯B(11)、(3 S,3a R)-3-羟乙基-3a,4,5,6-四氢苯酞(12)、(3 S,3a R,10 R)-(-)-10-羟基苯酞(13)、洋川芎内酯F(14)、新二聚藁本内酯(15)。其中,化合物1、2、8、12、13和15为首次从川芎中分离。所试化合物均对大鼠胸主动脉环有舒张作用,其中化合物1、10、15最高浓度(12μM)舒张率分别为65%、73%、93%(P<0.01),EC 50分别为8.8、8.2、6.2μM。化合物15(20μM)也能显著抑制细胞内钙离子浓度。构效分析发现,羟基取代位置对苯酞类成分血管舒张活性影响较大,另化合物1活性:消旋体>左旋体>右旋体。

To study on the phthalides with vasodilating activity of stems and leaves from Ligusticum chuanxiong.The compounds were isolated and purified by MCI,silica gel.etc.Finally,fifteen phthalides were isolated and identified,such as diangeliphthalide A(1),chaxiongnolide D(2),asepoxyligustilide(3),5-hydroxy-3-butylene-phthalide(4),senkyunolide B(5),3-butylidene-7-hydroxyphthalide(6),Z-ligustilide(7),Z-6-hydroxyl-7-methoxyligustilide(8),chuanxiongnolide B(9),levistolide A(10),tokinolideB(11),(3 S,3a R)-3-hydroxyethyl-3a,4,5,6-tetrahydrophthalide(12),(3 S,3a R,10 R)-(-)-10-hydroxyphenylphthalide(13),senkyunolide F(14),neodiligustilide(15).Compounds 1,2,8,12,13 and 15 were firstly isolated from the L.chuanxiong.All tested compounds showed vasodilation in rat thoracic aortic rings.The vasodilation rate of compounds 1,10 and 15 were 65%,73%and 93%at the highest concentrations(12μM)(P<0.01),respectively and EC 50 were 8.81,8.23,6.2μM,respectively.In addition,compound 15(20μM)significantly inhibited intracellular calcium concentration.The structure-activity analysis showed that hydroxyl substitution had significant effect on the vasodilative activity of phthalides.More importantly,it was found in the activity of compound 1 that enantiomeric(±)>enantiomeric(-)>enantiomeric(+).