金银花化学成分的分离鉴定与Aβ1-42聚集的抑制活性

Isolation and identification of the chemical constituents from the flower of Lonicera japonica Thunb. and the inhibition of self-induced Aβ1-42 aggregation

目的对金银花(Lonicera japonica Thunb.)的化学成分进行研究,并对分离得到的化合物测试β-淀粉样蛋白聚集抑制活性。方法采用水提醇沉法对金银花干燥花蕾进行提取,并用D101大孔吸附树脂、硅胶柱色谱、ODS柱色谱法和制备HPLC法对提取物的化学成分进行分离与纯化,并根据理化性质、NMR等波谱数据对化合物进行结构鉴定,以姜黄素作为阳性对照来检测其中的木脂素类化合物(1~6)对Aβ1-42聚集的抑制活性。结果共分离得到10个化合物,分别鉴定为forsythialanside C(1)、urolignoside(2)、icariside E4(3)、(7R,8S)-erythro-7,9,9′-trihydroxy-3,3′-dimethoxy-8-O-4′-neolignan-4-O-β-D-glucopyranoside(4)、(7S,8S)-threo-7,9,9′-trihydroxy-3,3′-dimethoxy-8-O-4′-neolignan-4-O-β-D-glucopyranoside(5)、(7S,8R)-erythro-7,9,9′-trihydroxy-3,3′-dimethoxy-8-O-4′-neolignan-4-O-β-D-glucopyranoside(6),8-hydroxygeraniol-8-O-β-D-glucoside(7),kankanoside P(8),(2E,6Z)-8-(β-D-glucopyranosyloxy)-2,6-dimethyl-2,6-octadienoic acid(9),lamiuamplexoside C(10)。化合物1和2在20μmol·L-1时的抑制活性分别为74.6%和85.2%,高于阳性对照姜黄素(62.1%)。化合物3~6表现出中等程度的Aβ1-42聚集抑制活性。结论化合物1~3和7~10为首次从忍冬属中分离得到,并且研究表明苯骈二氢呋喃新木脂素糖苷类化合物C-4位与葡萄糖成苷后能明显提高对β-淀粉样蛋白聚集的抑制活性。

Objective To study the chemical constituents of the flow er of Lonicera japonica Thunb.and the inhibition of self-induced Aβ1-42 aggregation.Methods D101 macroporous resin,Silica gel column chromatography,ODS column chromatography,Polyamide CC and semi-preparative HPLC methods w ere used for the separation and purification from the extract of the flow er of Lonicera japonica Thunb.Their structures w ere determined on the basis of spectral analysis.The inhibition of Aβ1-42 aggregation w as examined by a Th T-based fluorometric assay w ith curcumin as a positive control.Results Ten compounds w ere isolated and identified as urolignoside(1),icariside E4(2),forsythialanside C(3),(7 R,8 S)-erythro-7,9,9’-trihydroxy-3,3’-dimethoxy-8-O-4’-neolignan-4-O-β-D-glucopyranoside(4),(7 S,8 S)-threo-7,9,9’-trihydroxy-3,3’-dimethoxy-8-O-4’-neolignan-4-O-β-D-glucopyranoside(5),(7 S,8 R)-erythro-7,9,9’-trihydroxy-3,3’-dimethoxy-8-O-4’-neolignan-4-O-β-D-glucopyranoside(6),8-hydroxygeraniol-8-O-β-D-glucoside(7),kankanoside P(8),(2 E,6 Z)-8-(β-D-glucopyranosyloxy)-2,6-dimethyl-2,6-octadienoic acid(9),lamiuamplexoside C(10).The inhibitory activity of compounds 1 and 2 at 20μmol·L-1 w ere 74.6%and 85.2%,respectively,w hich w ere higher than that of the curcumin(62.1%).Compounds 3-6 show ed moderate Aβ1-42 aggregation activities,w ith the inhibition rates of 69.6%,62.5%,67.9%and 69.1%,respectively.Conclusion Compounds 1-3 and 7-10 are isolated from Lonicera genus for the first time.By comparison of the structure-activity relationship of the six compounds,the activities of the dihydrobenzofuran neolignan glycosides with an additional glucose moiety at C-4 are found to be superior compared with other compounds.