皖产桐桔梗提取物大鼠体内代谢产物鉴定及代谢途径分析

Metabolite identification and metabolic pathway analysis of Platycodonis Radix extracts from Tongcheng city in rats

研究桐桔梗在大鼠血浆、尿液、粪便中的原型成分和代谢产物,揭示其体内代谢途径及代谢规律。采用超高效液相色谱-串联四极杆飞行时间质谱(UPLC-Q-TOF-MS)及质量亏损过滤(MDF)技术对桐桔梗在大鼠体内的原型成分及代谢产物进行系统表征与辨识。采用ACQUITY UPLC BEH C18色谱柱(2.1 mm×100 mm,1.7μm),以0.1%甲酸水(A)-0.1%甲酸乙腈(B)为流动相进行梯度洗脱,在电喷雾质谱负离子模式下对生物样品进行分析。从灌胃给予桐桔梗提取物的大鼠血浆、尿液、粪便中共检测到12个皂苷类原型成分和27个代谢产物,其中血浆中共检测到11个原型成分和9个代谢产物,尿液中共检测到11个原型成分和8个代谢产物,粪便中共检测到10个原型成分和20个代谢产物。进一步研究表明,桐桔梗在大鼠体内的代谢途径主要包括氧化、还原、乙酰化、逐级水解脱糖、葡萄糖醛酸化等。该研究为阐明桐桔梗药效物质基础及作用机制提供了科学依据。

In this study, we delved into the prototypical components and metabolites of Platycodonis Radix extracts(PRE) from Tongcheng city in plasma, urine and feces of rats, and revealed its metabolic pathways and metabolic rules in vivo. The prototypical components and metabolites of PRE in rats were characterized and identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and mass defect filter(MDF). The biological samples were analyzed by ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm), with 0.1% formic acid water(A)-0.1% formic acid acetonitrile(B) as mobile phase, and the biological samples were analyzed in negative ion mode by electrospray ionization mass spectrometry(ESI-MS). Twelve prototypical saponins and twenty-seven metabolites were detected in plasma, urine and feces of rats treated with PRE by oral administration. Eleven prototypical components and nine metabolites were detected in plasma, eleven prototypical components and eight metabo-lites were detected in urine, and ten prototypical components and twenty metabolites were detected in feces. Further studies showed that the metabolic pathways of PRE in rats mainly include oxidation, reduction, acetylation, stepwise hydrolytic deglycosylation, glucuronidation and so on. This study provides a scientific basis for clarifying the pharmacological basis and mechanism of PRE from Tongcheng city.