微花藤脂溶性化学成分及其神经保护与钾通道阻断活性

Liposoluble constituents from Iodes cirrhosa and their neuroprotective and potassium channel-blocking activity

目的:研究微花藤Iodes cirrhosa的化学成分,并对分离化合物进行生物活性筛选。方法:利用多种色谱技术进行分离纯化,并通过现代波谱学鉴定其结构。通过去血清的方法建立JNK3转染细胞损伤模型对化合物的神经细胞保护活性进行评价。利用非特异性和特异性钾通道调节剂筛选模型对化合物的钾通道调节活性进行评价。结果:从微花藤根95%乙醇提取物的乙酸乙酯萃取部分分离得到21个化合物,分离鉴定为1β,3β-二羟基乌苏烷-9(11),12-二烯(1)、冬青醇乙酸酯(2)、3β-香树脂酮醇棕榈酸酯(3)、3β-乙酰氧基-乌苏-12-烯-11-酮(4)、白桦脂酸(5)、豆甾醇(6)、7β-羟基豆甾醇(7)、豆甾醇-3-O-β-D-吡喃葡萄糖苷(8)、东莨菪内酯(9)、东莨菪苷(10)、N-咖啡酰多巴(11)、异绿原酸甲酯(12)、异绿原酸(13)、2,6-二甲氧基-1,4-苯醌(14)、原儿茶醛(15)、香草醛(16)、原儿茶酸(17)、香草酸(18)、咖啡酸(19)、壬二酸(20)和丁二酸(21)。在1×10-6mol.L-1浓度时,化合物3,4,6,9,10,14,15,18,20对去血清后SH-SY5Y-JNK3细胞的抗损伤保护率分别为177%,144%,137%,137%,143%,145%,137%,189%和130%。化合物16在1×10-5mol.L-1浓度时在2种钾通道调节剂筛选模型上均使荧光强度增强。结论:化合物1为新化合物。所有化合物均为首次从薇花藤属植物中发现。化合物3,4,6,9,10,14,15,18,20对神经细胞具有抗损伤保护作用。化合物16具有钾通道阻断活性。

Objective：To study the chemical constituents of Iodes cirrhosa and evaluate their bioactivity.Method： The compounds were isolated and purified by various kinds of column chromatography methods and their structures were determined by spectroscopic data analysis.Neuroprotective assay against serum deprivation induced SH-SY5Y-JNK3 cell apoptosis was evaluated by MTT method while potassium channel-blocking activity was assayed in both non-specific and specific K＋ channel-regulator screening models.Result： Twenty-one compounds were obtained from an EtOAc portion of an ethanolic extract of the root of I.cirrhosa.Their structures were elucidated as 1β,3β-dihydroxyurs-9（11）,12-diene（1）,bauerenyl acetate（2）,3β-hydroxy-11-oxo-olean-12-enyl palmitate（3）,3β-acetoxy-urs-12-ene-11-one（4）,betulinic acid（5）,stigmasta-5,22-diene-3β-ol（6）,7β-hydroxystigmasterol（7）,stigmasta-5,22-diene-3β-ol 3-O-β-D-glucopyranoside（8）,scopoletin（9）,scopolin（10）,clovamide（11）,methyl 3,5-di-O-caffeoylquinate（12）,3,5-dicaffeoylquinic acid（13）,2,6-dimethoxy-1,4-benzoquinone（14）,protocatechualdehyde（15）,vanillin（16）,protocatechuic acid（17）,vanillic acid（18）,caffeic acid（19）,azelaic acid（20）,and succinic acid（21）.Compound 3,4,6,9,10,14,15,18 and 20 showed neuroprotective activities against serum deprivation induced SH-SY5Y-JNK3 cell apoptosis at a concentration of 1.0×10-6 mol·L-1 with relative protection rates of 177%,144%,137%,137%,143%,145%,137%,189%,130%,respectivley.Compound 16 could increase DiBAC4（3） fluorescence response in both non-specific and specific K＋ channel-regulator screening models at the concentration of 1.0×10-5 mol·L-1.Conclusion： Compound 1 was a new compound and all compounds were isolated from this genus for the first time.Compounds 3,4,6,9,10,14,15,18 and 20 showed neuroprotective activities while 16 exhibited K＋ channel-blocking activity.