华泽兰根化学成分及其抑制α-葡萄糖苷酶和蛋白酪氨酸磷酸酶1B的活性研究  

Chemical constituents from Eupatorium chinense roots and their inhibitory activities onα-glucosidase and protein tyrosine phosphatase 1B

作　　者：赵金诺 覃怡发 张轩 张梦娇 晏晶晶 梁皓皓 ZHAO Jin-nuo;QIN Yi-fa;ZHANG Xuan;ZHANG Meng-jiao;YAN Jing-jing;LIANG Hao-hao(Hubei Key Laboratory of Natural Products Research and Development(China Key Laboratory of Light Industry Functional Yeast),College of Biological and Pharmaceutical Sciences,China Three Gorges University,Yichang 443002,China)

机构地区：[1]三峡大学生物与制药学院天然产物研究与利用湖北省重点实验室(中国轻工业功能酵母重点实验室),宜昌443002

出　　处：《天然产物研究与开发》2024年第10期1698-1706,共9页Natural Product Research and Development

基　　金：国家级大学生创新创业训练计划(20231075023);天然产物研究与利用湖北省重点实验室(三峡大学)开放基金(2022NPRD03)。

摘　　要：为研究华泽兰Eupatorium chinense根部的化学成分及其抗糖尿病活性,采用正相硅胶柱色谱、薄层色谱、凝胶柱色谱及半制备高效液相色谱等色谱方法,从华泽兰根部分离得到15个单体化合物,并通过现代波谱技术鉴定其结构分别为:8 S-9-hydroxythymol(1)、8,10-dehydro-9-hydroxythymol(2)、1-[4-hydroxy-3-methoxy-5-(3-methylbut-3-en-1-ynyl)phenyl]wethanone(3)、speciosin L(4)、(R)-8-hydroxy-9-isobutyryloxythymol(5)、1,4-[13C]-1,2,3,4-tetrahydro-5-naphthyl-amin(6)、eupatriol(7)、3β,6-hydroxytremetone(8)、泽兰酮(9)、(2 R,3 S)-5-acetyl-6-hydroxyl-2-isopropenyl-3-ethoxy-dihydrofuran(10)、(2 R,3 S)-5-乙酰基-6-羟基-2-异丙烯基-3-乙氧基-苯并二氢呋喃(11)、6-羟基-2 H-苯并呋喃-3-酮(12)、3,5-dimethyl-2,3-dihydrobenzofuran(13)、2,4-bis-(5-acetyl-6-hydroxy-benzofuran-2-yl)-4-methyl-pent-1-ene(14)、1,1′-[[(2 E)-4-methylpent-2-ene-2,4-diyl]bis(6-hydroxy-1-benzofuran-2,5-diyl)]diethanone(15)。其中化合物3为首次从泽兰属植物中分离获得,化合物14为首次从华泽兰中分离获得。采用对硝基苯基-β-吡喃半乳糖苷法与对硝基苯磷酸盐法分别测定所有化合物对诱导糖尿病发生的α-葡萄糖苷酶和蛋白酪氨酸磷酸酶1B(PTP1B)的抑制活性进行评价,化合物3、4、5和12具有良好的α-葡萄糖苷酶抑制活性,其IC 50值分别为3.7、10.1、21.3、22.5μg/mL,其中化合物3的抑制活性优于良性药阿卡波糖(4.6μg/mL);化合物1、3、4和12具有良好的PTP1B抑制活性,其IC 50值分别为15.2、8.6、2.2和21.2μg/mL,其中化合物3的抑制活性优于良性药齐墩果酸(12.5μg/mL),化合物4的抑制活性优于阳性药正钒酸钠(7.5μg/mL)和齐墩果酸(12.5μg/mL)。研究表明,炔类化合物3和4均具有较明显的α-葡萄糖苷酶和PTP1B抑制活性。利用分子对接技术计算化合物3和4分别与α-葡萄糖苷酶和PTP1B的相互作用,结果表明化合物3和4与α-葡萄糖苷酶和PTP1B均具有较强的结合力。本�This study aims to investigate the chemical constituents of Eupatorium chinense roots and their antidiabetic activities.Normal-phase silica gel column chromatography,thin-layer chromatography,gel column chromatography and semi-preparative high-performance liquid chromatography were used to investigate the chemical constituents of roots of E.chinense.Fifteen compounds were isolated and then identified as 8 S-9-hydroxythymol(1),8,10-dehydro-9-hydroxythymol(2),1-[4-hydroxy-3-methoxy-5-(3-methylbut-3-en-1-ynyl)phenyl]ethenone(3),speciosin L(4),(R)-8-hydroxy-9-isobutyryloxythymol(5),1,4-[13C]-1,2,3,4-tetrahydro-5-naphthyl-amin(6),eupatriol(7),3β,6-hydroxytremetone(8),6-methoxyluteolin(9),(2 R,3 S)-5-acetyl-6-hydroxyl-2-isopropenyl-3-ethoxy-dihydrofuran(10),(2 R,3 S)-5-Acetyl-6-hydroxy-2-isopropenyl-3-ethoxy-benzodihydrofuran(11),6-hydroxy-2 H-benzofuran-3-one(12),3,5-dimethyl-2,3-dihydrobenzofuran(13),2,4-bis-(5-acetyl-6-hydroxy-benzofuran-2-yl)-4-methyl-pent-1-ene(14),1,1′-[[(2 E)-4-methylpent-2-ene-2,4-diyl]bis(6-hydroxy-1-benzofuran-2,5-diyl)]diethanone(15).Among them,compound 3 was isolated for the first time from Eupatorium and compound 14 was isolated for the first time from E.chinense.The inhibitory activities ofα-glucosidase and protein tyrosine phosphatase 1B(PTP1B)of the compounds were determined by p-nitrophenyl-β-galactopyranoside method and p-nitrophenyl phosphate method.Compounds 3,4,5 and 12 showed goodα-glucosidase inhibitory activity with IC 50 values of 3.7,10.1,21.3 and 22.5μg/mL,respectively,with compound 3 showing better inhibitory activity than the benign drug acarbose(4.6μg/mL);compounds 1,3,4 and 12 showed good PTP1B inhibitory activity with IC 50 values of 15.2,8.6,2.2 and 21.2μg/mL,respectively,of which the inhibitory activity of compound 3 was superior to that of the benign drug oleanolic acid(12.5μg/mL),and the inhibitory activity of compound 4 was superior to that of the positive drugs sodium orthovanadate(7.5μg/mL)and oleanolic acid(12.5μg/mL).It was shown that both alkyne com

关 键 词：华泽兰 化学成分 抗糖尿病活性 Α-葡萄糖苷酶 蛋白酪氨酸磷酸酶1B 

分 类 号：R284[医药卫生—中药学]