基于在体单向灌流模型分析类叶牡丹提取物中5种皂苷成分的肠吸收特性

In vivo Absorption Characteristics of 5 Saponins from the Extract of Caulophyllum robustum Maxim by One-way Perfusion

目的研究类叶牡丹提取物中主要皂苷成分的肠吸收特性。方法建立HPLC-MS/MS测定方法,通过大鼠在体单向肠灌流模型,探讨吸收部位、药物浓度及P-糖蛋白(P-gp)抑制剂对类叶牡丹提取物中皂苷成分肠吸收特征。结果Cauloside G、Cauloside H、Leonticin D 3个成分的吸收速率常数和渗透系数在十二指肠段最大,Cauloside C和Cauloside D则表现出回肠的强吸收;药物浓度为5.0 mg/mL时,呈现最强吸收,随药物浓度的增加吸收无明显变化;加入P-gp抑制剂维拉帕米后,渗透系数明显提高。结论十二指肠和回肠是药物主要吸收场所,各成分的吸收与浓度不呈现剂量依赖关系,抑制P-gp的表达可促进类叶牡丹有效成分的吸收;研究结果可为类叶牡丹的新药开发提供科学参考。

Objective To study the intestinal absorption characteristics of the main saponins in the extract of phyllostonia.Methods To establish HPLC/MS/MS method,through the unidirectional intestinal perfusion model rats in vivo,and to explore the intestinal absorption characteristics of the saponin component in the extract of Peony-like leaves by absorption sites,drug concentration and P-glycoprotein(P-gp)inhibitors.Results The absorption rate constants(Ka)and permeability coefficients(Peff)of Cauloside G,Cauloside H and Leonticin D are the largest in duodenum,while Cauloside C and Cauloside D show strong ileum absorption.When the drug concentration is 5.0 mg/mL,it shows the strongest absorption,and the absorption do not change significantly with the increase of the drug concentration;after adding the P-gp inhibitor verapamil,the permeability coefficient increased significantly.Conclusion The duodenum and ileum are the main drug absorption sites,and the absorption and concentration of each component do not show a dose-dependent relationship.Inhibiting the expression of P-gp can promote the absorption of the effective components in leaflike peony.This study can provide a scientific reference for the developent of new drugs in Caulophyllum robustum.