江南山梗菜中1个新的三萜类化合物及其生物活性研究

A new triterpenoids and biological activities from Lobelia davidii

目的对江南山梗菜Lobelia davidii中的三萜类成分及其生物活性进行研究。方法采用硅胶柱色谱、Sephadex LH-20及HPLC等色谱技术进行分离纯化,运用NMR、MS等波谱技术进行化合物的结构鉴定。采用四甲基偶氮唑盐[3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide,MTT]法筛选分离得到化合物对人非小细胞肺癌A549细胞的细胞毒性;采用4-硝基苯基-α-D-吡喃葡萄糖苷(4-nitrophenyl-α-D-glucopyranoside,PNPG)法测定分离得到化合物对α-葡萄糖苷酶的抑制活性。结果从江南山梗菜的醋酸乙酯部位中分离得到6个三萜类化合物,分别鉴定为3β-正十六酸酯-齐墩果烷-12-烯-11-酮(1)、熊果酸(2)、齐墩果酸(3)、sumaresinolic acid(4)、3β-羟基-齐墩果烷-12-烯-11-酮(5)、32,33,34-三甲基-细菌藿烷-16-烯-3-O-β-D-吡喃葡萄糖苷(6)。细胞毒活性筛选结果表明,化合物1和5对A549细胞增殖有显著的抑制活性,其半数抑制浓度(median inhibition concentration,IC_(50))分别为(26.72±2.05)、(36.70±3.43)μmol/L。α-葡萄糖苷酶抑制活性筛选结果表明,化合物2和3对α-葡萄糖苷酶有较强的抑制活性,其IC_(50)分别为(28.97±1.73)、(11.87±1.18)μmol/L,抑制活性均高于阳性药阿卡波糖;化合物1对α-葡萄糖苷酶抑制活性的IC_(50)为(148.47±2.09)μmol/L,抑制活性与阳性药阿卡波糖相当。结论化合物1为新化合物,命名为山梗菜萜A;化合物2~6均为首次从江南山梗菜中分离得到。化合物1和化合物5对A549细胞有较强的细胞毒活性。化合物1~3对α-葡萄糖苷酶有一定的抑制活性。

Objective To study the chemical constituents and biological activities of triterpenoids from Lobelia davidii.Methods The chemical constituents were isolated and purified by silica gel,Sephadex LH-20 and HPLC.The chemical structures were identified by the spectroscopic methods(NMR and MS).The cytotoxic activities to the human non-small-cell lung cancer A549 cells of the compounds were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide(MTT)assay.Moreover,theα-glycosidase inhibitory activity of the compounds were determined by 4-nitrophenyl-α-D-glucopyranoside(PNPG)assay.Results Six triterpenoids were isolated from L.davidii.and identified as 3β-hexadecanoate-olean-12-en-11-one(1),ursolic acid(2),oleanic acid(3),sumaresinolic acid(4),3β-hydroxy-olean-12-en-11-one(5),and 32,33,34-trimethyl-bacteriohopan-16-ene 3-O-β-D-glucopyranoside(6).The screening results showed that compounds 1 and 5 had strong inhibitory activity for the A549 cells with the IC(50)value of(26.72±2.05)μmol/L and(36.70±3.43)μmol/L.While compounds 2 and 3 had strong inhibitory activities againstα-glycosidase with the IC(50)values of(28.97±1.73)and(11.87±1.18)μmol/L,respectively,which were higher than that of acarbose,and compound 1 exhibted moderate inhibitory activities againstα-glycosidase with the IC(50)value of(148.47±2.09)μmol/L,which was similar to acarbose.Conclusion Compound 1 is a new compound named davidioterpene A.Compounds 2-6are isolated from L.davidii for the first time.Compounds 2 and 5 have strong inhibitory activity against A549 cells.Compounds 1-3are found to have definiteα-glycosidase inhibitory activity.