基于在体单向肠灌流模型的红车轴草异黄酮类成分渗透性研究  

Study on Intestinal Permeability of Isoflavones in Trifolium pretense L.Based on in situ Single Pass Intestinal Perfusion Model

作　　者：罗立宇 吴宏伟[2] 赵海誉[2] 高文远[1] LUO Liyu;WU Hongwei;ZHAO Haiyu;GAO Wenyuan(School of Pharmaceutical Science and Technology,Tianjin University,Tianjin 300072,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]天津大学药物科学与技术学院,天津300072 [2]中国中医科学院中药研究所,北京100700

出　　处：《中国中医药信息杂志》2020年第11期89-95,共7页Chinese Journal of Information on Traditional Chinese Medicine

摘　　要：目的研究红车轴草水提物的异黄酮类肠吸收成分及其肠渗透性,探讨其相应机制。方法采用超高效液相色谱串联质谱法(UPLC-MS/MS),建立红车轴草水提物肠灌流液中异黄酮类成分大豆苷元、大豆苷、染料木苷、毛蕊异黄酮葡萄糖苷、芒柄花素、芒柄花苷的定量分析方法。基于大鼠在体单向肠灌流模型,研究红车轴草水提物中6种异黄酮类成分在不同小肠段(十二指肠、空肠、回肠)的肠渗透性,并对不同浓度的芒柄花素、芒柄花苷单体成分肠渗透特征进行研究。结果建立了红车轴草水提物肠灌流液中6种异黄酮类成分的UPLC-MS/MS定量分析方法,符合方法学要求。红车轴草水提物灌流液各成分的有效渗透系数(Peff)均大于5×10-5 cm/s,最大者为芒柄花素(Peff=3.20,十二指肠),其次为染料木苷(Peff=2.19,空肠);对于不同肠段,各成分Peff和吸收速率常数(Ka)均存在一定差异,大豆苷元、芒柄花素的十二指肠Peff最大,其余4种成分的空肠Peff最大,表明红车轴草水提物中异黄酮的最佳吸收窗口为十二指肠和空肠;不同浓度芒柄花素、芒柄花苷单体灌流的Peff、Ka差异均无统计学意义(P>0.05),吸收曲线近似线性,其吸收机制符合被动扩散的特征。结论本研究初步明确了红车轴草水提物中异黄酮类成分的肠渗透性及吸收机制,可为质控成分筛选、制剂开发及临床合理用药提供参考。Objective To study the isoflavone intestinal absorption components and intestinal permeability of water extracts of Trifolium pretense L.;To explore the corresponding mechanism.Methods An ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was adopted.A quantitative analysis method for the isoflavone components of isoflavoues daidzein,daidzin,genistein,mullein isoflavone glucoside,formononetin,ononin in the intestinal perfusate of water extracts of Trifolium pretense L.was established.In situ single-pass intestinal perfusion model was used to study the intestinal permeability of the six isoflavones in the water extracts of Trifolium pretense L.in different small intestine segments(duodenum,jejunum,and ileum).The intestinal penetration characteristics of formononetin and ononin at different concentrations were studied.Results The UPLC-MS/MS quantitative analysis method of 6 isoflavones in intestinal perfusate of Trifolium pretense L.was established,which met the methodological requirements.The effective permeability coefficient(Peff)of the components from the water extracts were all greater than 5×10-5 cm/s.Of the six isoflavones,the maximum value of Peff was formononetin(Peff=3.20,duodenum),followed with genistein(Peff=2.19,jejunum).For the different intestinal segments,the Peff and absorption rate constant(Ka)of the components were different.Daidzein and formononetin had the maximum Peff at the duodenum.The other four components had the maximum Peff at the jejunum.The results indicated that the best effective absorption locations for the isoflavones in the water extracts were the duodenum and jejunum.There was no statistical significance in Peff and Ka(P>0.05)for formononetin and ononin in different concentrations,and the absorption curve was approximately linear.Therefore,the absorption mechanisms of formononetin and ononin were both passive diffusion.Conclusion This study has preliminarily clarified the intestinal permeability and absorption mechanism of isoflavones in the water

关 键 词：在体单向肠灌流 渗透性 红车轴草 异黄酮 芒柄花素 芒柄花苷 

分 类 号：R284.1[医药卫生—中药学] R285.5[医药卫生—中医学]