Identification and quantitative investigation of the effects of intestinal microflora on the metabolism and pharmacokinetics of notoginsenoside Fc assayed by liquid chromatography with electrospray ionization tandem mass spectrometry
Identification and quantitative investigation of the effects of intestinal microflora on the metabolism and pharmacokinetics of notoginsenoside Fc assayed by liquid chromatography with electrospray ionization tandem mass spectrometry
复制标题
液相色谱-电喷雾串联质谱法鉴定和定量研究肠道菌群对三七皂苷Fc代谢和药代动力学的影响
DOI：
10.1002/jssc.201801237
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发表时间：
2019-05-01
影响因子：
3.1
通讯作者：
Wang, Zhengtao
中科院分区：
文献类型：
--
作者：
Ju, Zhengcai;Li, Jia;Wang, Zhengtao
Notoginsenoside Fc 是从三七叶中分离出来的原人参二醇型皂苷，具有特殊的抗血小板聚集作用。为了研究胃肠内容物对代谢特征和药代动力学的调节作用，使用伪无菌大鼠来研究细菌群落结构对代谢特征的影响。使用分光光度法测量糖苷酶活性。使用超高效液相色谱和串联四极杆/飞行时间质谱法系统地研究了三七皂苷 Fc 在正常和伪无菌大鼠肠道微生物群中的生物转化。建立了同时测定三七皂苷Fc原型及其降解产物的液相色谱-串联质谱法。通过体内药代动力学研究，比较正常大鼠和伪无菌大鼠的药代动力学特征。在体外生物转化过程中，在正常大鼠肠道细菌中孵育后，检测到并鉴定出七种去糖基化产物。在伪无菌大鼠中，糖苷酶活性显着降低，且未发生明显降解。在一项体内研究中，全身暴露量显着增加了40%，从零到无穷大的血药浓度-时间曲线下面积和半衰期值即可证明，伪无菌组的半衰期比正常大鼠延长得更多。结果表明，使用肠道细菌代谢草药（如三七）的患者应了解肠道细菌的概况，以确保治疗效果。
Notoginsenoside Fc, which is a protopanaxdiol-type saponin isolated from the leaves of Panax notoginseng, exhibits an exceptional antiplatelet aggregatory effect. To study the modulating effect of gastrointestinal contents on the metabolic profile and pharmacokinetics, pseudo germ-free rats were used to study the influence of the bacterial community structure on the metabolic profile. Glycosidase activities were measured using the spectrophotometric method. Biotransformations of notoginsenoside Fc in normal and pseudo germ-free rat intestinal microflora were systematically investigated using ultra high performance liquid chromatography with tandem quadrupole/time-of-flight mass spectrometry. Moreover, a liquid chromatography with tandem mass spectrometry method was established for simultaneous determination of the notoginsenoside Fc prototype and its degradation products. Through an in vivo pharmacokinetic study, the pharmacokinetic characteristics were compared between normal rats and pseudo germ-free rats. During the in vitro biotransformation, seven deglycosylated products were detected and identified after incubation in the intestinal bacteria of normal rats. In pseudo germ-free rats, glycosidase activities were significantly decreased, and no obvious degradation occurred. In an in vivo study, the systemic exposure was significantly increased 40%, as evidenced by the area under the blood concentration-time curve from time zero to infinity value and half-life value, which were prolonged more in the pseudo germ-free group than in normal rats. The results demonstrate that patients who use intestinal bacteria-metabolized herbs, such as panax notoginseng, should understand the profile of intestinal bacteria to ensure therapeutic efficacy.