Research On The Difference Of The Absorption And Metabolism Between Flavonoids In Epimedium Fried With Suet Oil Before And After And The Difference Of Its Self-assembled Nanomicelles’ Absorption

Epimedium is traditional tonic medicine of Chinese traditional medicine recorded in "Shen Nong’s Materia Medica". The main active ingredients of Epimedium are baohuoside I, icariin, epimedins A, B, C, which have efficacy of kidney yang, strong bones and muscles, rheumatism. In clinical, suet oil has been widely used in the processing of Epimedium, and its shcurative effect is extremely remarkable. Our previous research found that the absorption and metabolism of flavonoid glycosides in Epimedium are differences in vivo and in vitro. Absorption of multistage glucoside is lower than that of secondary glycosides (epimedin A, B, C<icariin<baohuoside I). In the processing process,"Heating" produced bioactive flavonoids (such as icariin, baohuoside I) which were absorbed more easily. But whether the change of Epimedium flavonoids permeability coefficient converted to the enhanced bioavailability and effect after processing, the influence of suet oilt on the absorption of Epimedium flavonoids, as well as the enhancement mechanism of Epimedium fried with suet oil need further research. Thus, we research the absorption, metabolism and excretion process of epimedin B and C from the pharmacokinetic perspective use the rat model. The pharmacological effect method was used to research the differences of absorption of raw and different processed Epimedium. The processing mechanism of Herba Epimedii was further explored from quality and quantity ditermination. Based on the formation of self-assembled nanomicelles, explaining the suet oil promotes the absorption of Epimedium flavonoids and the synergistic mechanisms, which provides the scientific basis for the accessories concocted theory.Firstly, this paper discusses the application of Chinese medicine pharmacokinetics in concocted Chinese medicine. Secondly, combined with the subject research foundation, the researches are following:(1) Middle pressure preparative system combined autopurification system was developed to purity Epimedins A, B, C as reference standards from the crude extract of Epimedium brevicornum Maxim, wahich lays the foundation for the subsequent metabolism experiments.(2) Using UPLC/Q-TOF analysis for the identification of epimedin B uptake into rat in vivo prototype and its metabolites, clarifiing the metabolic pathways of major metabolites in plasma, bile, urine, feces in in, revealing the variation rule of epimedin B in vivo from the qualitative point of view. (3) Using UPLC/Q-TOF analysis for the identification of epimedin C uptake into rat in vivo prototype and its metabolites, clarifiing the metabolic pathways of major metabolites in plasma, bile, urine, feces in in, revealing the variation rule of epimedin C in vivo from the qualitative point of view.(4) Using pharmacological effect method to research the influence of sheep fat which is one of classic processing accessories on the pharmacokinetics characteristic parameters of total flavonoids in Epimedium extract. Selecting the kidney yang certificate model caused by hydrocortisone, taking the SOD value and MDA as indicators to obtain the relationship between effective equivalent body stock and time, then calculating the apparent pharmacokinetic parameters. Thus, the rationality of its concocted medication can be explored.(5) Selecting icariin and baohuoside I as representatives, research the vectorial transport in Caco-2cell monolayers and the absorption in rat intestine of the formed self-assembled nanomicelles under the action of suet oil. Thus, a tentative interpretation of the enhancement of activity seen with Epimedium fried with suet oil can be provided.Therefore, the processing mechanism of Epimedium can be explored as:The content of main active flavonoids in Epimedium changed after heating process. The content of icariin and baohuoside I were both increased. At the same time, processing accessories" suet oil" would further improve the bioavailability of flavonoids in vivo, and the formed self-assembled nanomicelles under the action of suet oil promoted the absorption of flavonoids in Caco-2cell monolayers and in rat intestine. These reveal suet oil has the function of promoting absorption of Epimedium flavonoids. Thereby, it enhances the efficacy.