UPLC-Q-TOF-MS分析姜黄乙酸乙酯提取物抑制表皮生长因子受体活性的成分

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目的:应用均相时间分辨荧光(homogeneous time-resolved fluorescence,HTRF)技术,筛选发现具有抑制表皮生长因子受体(epidermal growth factor receptor,EGFR)活性的姜黄提取物,同时采用超高效液相色谱与串联四级杆飞行时间质谱仪联用技术(ultra-performance liquid chromatography/quadrupole time-offlight mass spectrometry,UPLC/Q-TOF-MS)对其活性部位进行分析和鉴别。方法:药材经石油醚渗滤、乙醇提取、乙酸乙酯萃取和水煎煮后,得到4个提取部位。采用HTRF法检测姜黄乙酸乙酯提取物对ERFR的抑制作用,计算提取物对EFFR的抑制率。采用ACQUITY UPLC BEH C18色谱柱,以0.1%甲酸水溶液(A)-乙腈(B)为流动相梯度洗脱,200~400 nm扫描,使用ESI离子源,在正离子模式下采集数据。结果:姜黄的乙酸乙酯部位显示较强的EGFR抑制活性,并从其活性部位中分析鉴定出9个化学物,主要成分为姜黄素类化合物,其中6个分别是香豆酸、姜黄酮、双去甲氧基姜黄素、去甲氧基姜黄素、姜黄素、1-(4-羟基-3,5-二甲氧基苯基)-7-(4-羟基-3-甲氧基苯基)-1,6-庚二烯-3,5-二酮,3个未知成分。结论:研究发现姜黄乙酸乙酯提取部位具有较强的EGFR抑制活性,IC50为3.621μg·mL-1,根据Q-TOF-MS测定的相对分子质量及正离子信息,鉴定了姜黄乙酸乙酯提取物主要为姜黄素类成分,其中以姜黄素、去甲氧基姜黄素、双去甲氧基姜黄素为主要活性成分,说明姜黄素类化合物为抑制EGFR活性的主要成分,为其在抗癌方面的应用提供理论依据,同时为进一步跟踪分离活性成分奠定基础。 OBJECTIVE: To screen the curcumin extract with inhibitory activity of epidermal growth factor receptor (EGFR) by homogeneous time-resolved fluorescence (HTRF) technique. The effects of ultra-high performance liquid chromatography The active sites were analyzed and identified by using ultra-performance liquid chromatography / quadrupole time-offlight mass spectrometry (UPLC / Q-TOF-MS). Methods: The medicinal materials were obtained by petroleum ether diafiltration, ethanol extraction, ethyl acetate extraction and decoction. Four extraction sites were obtained. HTRF method was used to detect the inhibition of ERFR by the extract of turmeric ethyl acetate, and the inhibition rate of extract to the EFFR was calculated. The data were collected in positive ion mode using an ACQUITY UPLC BEH C18 column eluting with a mobile phase of 0.1% formic acid in water (A) - acetonitrile (B) with a 200-400 nm scan using an ESI ion source. Results: The ethyl acetate fraction of turmeric showed a strong EGFR inhibitory activity. Nine chemicals were identified from the active sites of turmeric, the main constituents were curcuminoids, of which 6 were curcumin, curcumin, Didemethoxycurcumin, demethoxycurcumin, curcumin, 1- (4-hydroxy-3,5- dimethoxyphenyl) -7- (4-hydroxy-3-methoxybenzene Yl) -1,6-heptadiene-3,5-dione, three unknown ingredients. Conclusion: The extract of turmeric ethyl acetate has strong EGFR inhibitory activity with IC50 of 3.621 μg · mL-1. According to the relative molecular mass and positive ion information determined by Q-TOF-MS, the extraction of ethyl acetate from turmeric Curcumin, curcumin, demethoxycurcumin, bis-methoxymethionine curcumin as the main active ingredient, curcumin compounds inhibit the activity of EGFR as the main component of its anti-cancer It provides a theoretical basis for further application in tracking the separation of active ingredients.
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