耳叶牛皮消中C21甾体成分在功能性消化不良模型大鼠中的胆汁排泄及其代谢产物的鉴定

Biliary Excretion and Metabolite Identification of C21 Steroid Components of Cynanchum Auriculatum extract in Functional Dyspepsia Rat model

关键词:  耳叶牛皮消  胆汁  排泄  代谢  功能性消化不良

Key words:  Cynanchum auriculatum  bile  excretion  metabolic  functional dyspepsia

摘要:

摘要：目的 研究耳叶牛皮消提取物中C21甾体成分青阳参苷元、去酰基萝藦苷元在正常及功能性消化不良(FD)模型大鼠胆汁中的排泄情况及其代谢产物。方法 正常SD大鼠采用灌胃冰盐酸结合不规则饲养的方式诱导FD模型。按0.1 g·(100 g)-1剂量灌胃耳叶牛皮消提取物后分别在不同时间段收集大鼠胆汁。采用UPLC-MS/MS和UHPLC Q-Exactive Plus Orbitrap HRMS分析技术分别测定和鉴定两种成分在胆汁中的排泄量和代谢产物。结果 青阳参苷元和去酰基萝藦苷元在不同病理生理状态下大鼠胆汁中的累积排泄率为0.09%~0.19%，与正常组相比，模型组中去酰基萝藦苷元的累积排泄率显著降低(P<0.05)。FD大鼠胆汁中共鉴定出青阳参苷元和去酰基萝藦苷元的原型成分及其24种相关代谢产物，其代谢途径包括Ⅰ相代谢反应(脱水、还原、氧化等)和Ⅱ相代谢反应(硫酸化、乙酰化、葡萄糖醛酸结合等)。结论 耳叶牛皮消中C21甾体成分在胆汁中原型排出量较少且存在广泛的代谢途径，同时代谢会受到病理状态的影响。

Abstract:

ABSTRACT: OBJECTIVE To study the excretion characteristics and metabolite of C21 steroid components (qingyangshengenin and deacylmetaplexigenin) in Cynanchum auriculatum (CA) extract in the bile of rats based on the normal and functional dyspepsia (FD) states. METHODS FD rats were induced by intragastrically administrating ice-hydrochloric acid combined with irregular rearing. The bile was collected in different time periods after rats were intragastrically administrated CA extract at a dosage of 0.1 g·(100 g)-1, and then UPLC-MS/MS and UHPLC Q-Exactive Plus Orbitrap HRMS were used to determine and identify the cumulative excretion and metabolites of the two components in bile. RESULTS The ratios of cumulative excretion of qingyangshengenin and deacylmetaplexigenin in bile were determined within 0.09%~0.19% under different pathophysiological states. The cumulative excretion ratio of deacylmetaplexigenin in FD group was significantly lower than that in the normal group (P<0.05). Two prototype components and their forty-four metabolites were detected in bile of FD group, which mainly occurred Phase Ⅰ metabolic reactions (dehydration, reduction, oxidation, ect.) and Phase Ⅱ metabolic reactions (sulfation, acetylation, glucuronide conjugation, ect.). CONCLUSION The excretion of the two C21 steroid components in CA extract are low in bile. There may be a wide range of metabolic pathways for t qingyangshengenin and deacylmetaplexigenin, and the metabolism is affected by pathological state.