目的 采用液质联用方法对石榴皮鞣质在大鼠尿样中的代谢产物进行研究。方法 收集给药后大鼠的尿样,采用Venusil MP-C18色谱柱(4.6 mm×250 mm,5 μm),流动相乙腈-0.1%甲酸水溶液梯洗脱,检测波长256 nm;以电喷雾质谱检测,扫描范围m/z100~1 000,在负离子模式下扫描,参照相关文献,并结合药物在体内的代谢规律,推测石榴皮鞣质在大鼠尿样中可能的代谢产物。结果 在大鼠的尿液中共检测到7种代谢产物,根据其二级质谱及相关文献初步鉴定了其中6个代谢产物的结构,分别是U-1(尿石素), U-2(甲醚化尿石素A),U-3(尿石素A),U-4(甲基化尿石素A) ,U-5(鞣花酸),U-6(尿石素 C)。结论 石榴皮鞣质灌胃给药后,在大鼠体内主要发生水解、葡萄糖醛酸化苷化、分解、甲基化反应,生成尿石素一系列衍生物,该研究初步探明石榴皮鞣质在大鼠体内可能的代谢通路和药效物质基础。
Abstract
OBJECTIVE To study the in vivo metabolism of granatum tannins by liquid chromatography-mass spectrometry and clarify their metabolic pathways. METHODS The rat urine samples were collected after intragastric administration of tannins preparation of Punica granatum L. husk. The analysis was performed on a Venusil MP-C18 column with gradient elution system of acetonitrile and water containing 0.1% formic acid. Using electrospray ionization (ESI) in negative ion mode with scanning range from m/z 100 to 1 000, the metabolites were identified by comparing the MS spectra and MS data with the literatures. RESULTS Seven metabolites were detected in the rat urine, among which six were identified according to their second mass spectra to be U-1 (urolithin B), U-2(urolithin A methyl ether), U-3(urolithin A), U-4(urolithin A glucuronide), U-5(ellagic acid)and U-6(urolithin C). CONCLUSION Tannins in Punica granatum L. husk are metabolized after oral administration mainly through hydrolysis, glucuronidation glycosidation, decomposition and methylation reaction to generate a series of derivatives of urolithin. These results preliminarily indicate the metabolic pathway and material basis of the pharmacological activity of tannins in Punica granatum L. husk in rats.
关键词
鞣质 /
石榴 /
代谢产物 /
液质联用
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Key words
tannin /
Punica granatum L. husk /
metabolite /
LC-MS
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中图分类号：
R284
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参考文献
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