川芎茎叶中血管舒张活性苯酞类成分研究

Discovery of phthalides with vasodilating activity in stems and leaves of Ligusticum chuanxiong

目的研究川芎Ligusticum chuanxiong茎叶醇提物具有舒张血管活性的苯酞类成分。方法采用MCI、硅胶、Sephadex LH-20、中压液相色谱、半制备高效液相色谱等方法进行研究。并比较了苯酞和苯酞二聚体对离体大鼠胸主动脉环的舒张作用。结果从川芎茎叶中分离出10个苯酞化合物,分别鉴定为Z-3-丁烯基苯酞(1)、洋川芎内酯-E(2)、Z-洋川芎内酯-H(3)、(3Z,7β)-3-丁烯基-7-羟基-4,5,6,7-四氢苯酞(4)、新藁本内酯(5)、Z,Z′-3.3′a,7.7′a-双藁本内酯(6)、3Z,3Z′-6,8′,7,3′-双藁本内酯(7)、Z-东当归内酯A(8)、(3′Z)-(3S,8R,3a′S,6′R)-4,5-去氢-3.3′a,8.6′-双藁本内酯(9)、(3Z)-(3a R,6S,3′R,8′S)-3a.8′,6.3′-双藁本内酯(10)。化合物1、6~9能显著降低氯化钾预收缩大鼠胸主动脉环的张力。其中化合物6~8最高浓度(12μmol/L)舒张率分别为60%、52%、70%,半数有效浓度(EC50)分别为9.46、11.86、8.73μmol/L。结论所有化合物均为首次从川芎茎叶中分离得到,化合物6和8为首次从川芎中分离。受试化合物均有舒张血管活性,且二聚体的活性优于单苯酞。

Objective To study the phthalides with vasodilating activity of alcohol extracts from stems and leaves of Ligusticum chuanxiong.Methods Compounds were isolated by extensive chromatographic techniques including MCI,silica gel,Sephadex LH-20,ODS,and semi-preparative HPLC.The vasodilating effect of phthalide and dimer phthalide on thoracic aortic ring in vitro was investigated.Results Ten phthalides were isolated and identified,and their structures were elucidated as Z-3-butylidenephthalide(1),senkyunolide-E(2),Z-senkyunolide-H(3),(3 Z,7β)-3-butenyl-7-hydroxy-4,5,6,7-tetrahydrophthalide(4),neoligustilide(5);Z,Z′-3.3′a,7.7′a-diligustilide(6),3 Z,3 Z′-6,8′,7,3′-diligustilide(7),Z-tokinolide A(8),(3′Z)-(3 S,8 R,3 a′S,6′R)-4,5-dehydro-3.3′a,8.6′-diligustilide(9),and(3 Z)-(3 a R,6 S,3′R,8′S)-3 a.8′,6.3′-diligustilide(10).Compound 1,6—9 significantly reduced the strain of thoracic aortic ring in KCl preconstricted rats.The diastolic rate of compounds 6—8 were 60%,52%and 70%at the highest concentrations(12μmol/L),respectively.The EC50 was 9.46,11.86 and 8.73μmol/L,respectively.Conclusion All compounds are firstly isolated from the stems and leaves of L.chuanxiong.Compounds 6,8 are firstly isolated from L.chuanxiong.The test compounds could dilate blood vessels,and the activity of dimer phthalide was better than that of phthalide.