Targeted isolation and identification of bioactive compounds lowering cholesterol in the crude extracts of crabapples using UPLC-DAD-MS-SPE/NMR based on pharmacology-guided PLS-DA
Targeted isolation and identification of bioactive compounds lowering cholesterol in the crude extracts of crabapples using UPLC-DAD-MS-SPE/NMR based on pharmacology-guided PLS-DA
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基于药理学引导的 PLS-DA，利用 UPLC-DAD-MS-SPE/NMR 靶向分离和鉴定海棠粗提物中降低胆固醇的生物活性化合物
DOI：
10.1016/j.jpba.2017.11.061
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发表时间：
2018
影响因子：
3.4
通讯作者：
Hu Kaifeng
中科院分区：
文献类型：
--
作者：
Wen Chao;Wang Dongshan;Li Xing;Huang Tao;Huang Cheng;Hu Kaifeng
采用正交试验设计，研究了红宝石海棠、平邑甜茶、平邑甜茶、沙拐枣粗提物的降血脂作用。Rehd.和海棠（Malus prunifolia（Willd.）博克在高脂饮食诱导的肥胖（HF DIO）小鼠上进行评价。结果表明，这些提取物中的一些可以降低HF DIO小鼠的血清胆固醇水平。还通过LC-MS在正离子和负离子模式下对相同的提取物进行了质谱分析。根据药理实验结果，采用偏最小二乘判别分析（PLS-DA）和独立样本t检验，筛选出22个与抗高血压作用相关的LC-MS变量。在生物活性相关LC-MS信号的指导下，利用UPLC-DAD-MS-SPE对10个化合物进行了靶向分离和富集，并通过NMR和MS/MS鉴定/鉴定为柠檬酸（1）、对香豆酸（2）、金丝桃苷（3）、杨梅苷（4）、柚皮素（5）、槲皮素（6）、山奈酚（7）、龙胆苦苷（8）、熊果酸（9）和8-epiloganic acid（10）。在这10种化合物中，6种化合物，金丝桃苷（3）、杨梅苷（4）、柚皮素（5）、槲皮素（6）、山萘酚（7）和熊果酸（9），被单独研究并报道确实具有降低血清脂质水平的作用。这些结果证明了这种药物发现策略的有效性。与传统的从植物提取物中发现生物活性化合物的方法不同，基于药理学引导的PLS-DA的LC-MS数据，利用UPLC-DAD-MS-SPE/NMR技术对植物粗提物中的生物活性化合物进行靶向分离和鉴定，为天然产物的药物发现研究提供了一种新的高效去重复方法。
The anti-hyperlipidemic effects of crude crabapple extracts derived from Malus ‘Red jade’, Malus hupehensis (Pamp.) Rehd. and Malus prunifolia (Willd.) Borkh. were evaluated on high-fat diet induced obese (HF DIO) mice. The results revealed that some of these extracts could lower serum cholesterol levels in HF DIO mice. The same extracts were also parallelly analyzed by LC–MS in both positive and negative ionization modes. Based on the pharmacological results, 22 LC–MS variables were identified to be correlated with the anti-hyperlipidemic effects using partial least square discriminant analysis (PLS-DA) and independent samplest-test. Further, under the guidance of the bioactivity-correlated LC–MS signals, 10 compounds were targetedly isolated and enriched using UPLC-DAD-MS-SPE and identified/elucidated by NMR together with MS/MS as citric acid(1),p-coumaric acid(2), hyperoside(3), myricetin(4), naringenin(5), quercetin(6), kaempferol(7), gentiopicroside(8), ursolic acid(9) and 8-epiloganic acid(10). Among these 10 compounds, 6 compounds, hyperoside(3), myricetin(4), naringenin(5), quercetin(6), kaempferol(7) and ursolic acid(9), were individually studied and reported to indeed have effects on lowering the serum lipid levels. These results demonstrated the efficiency of this strategy for drug discovery. In contrast to traditional routes to discover bioactive compounds in the plant extracts, targeted isolation and identification of bioactive compounds in the crude plant extracts using UPLC-DAD-MS-SPE/NMR based on pharmacology-guided PLS-DA of LC–MS data brings forward a new efficient dereplicated approach to natural products research for drug discovery.