Intestinal Transport of 3,6′-Disinapoylsucrose, A Major Active
                    Component of Polygala tenuifolia, Using Caco-2 Cell Monolayer and In
                        Situ Rat Intestinal Perfusion Models

Ying Chen; Xinmin Liu; Ruile Pan; Xiaoxin Zhu; André Steinmetz; Yonghong Liao; Ning Wang; Bo Peng; Qi Chang

doi:10.1055/s-0033-1350794

Planta Medica, Table of Contents

Planta Med 2013; 79(15): 1434-1439
DOI: 10.1055/s-0033-1350794

Pharmacokinetic Investigations

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Intestinal Transport of 3,6′-Disinapoylsucrose, A Major Active Component of Polygala tenuifolia, Using Caco-2 Cell Monolayer and In Situ Rat Intestinal Perfusion Models

Ying Chen

¹Institute of Medicinal Plant Development, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, P. R. China

²Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, P. R. China

,

Xinmin Liu

¹Institute of Medicinal Plant Development, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, P. R. China

,

Ruile Pan

¹Institute of Medicinal Plant Development, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, P. R. China

,

Xiaoxin Zhu

²Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, P. R. China

,

André Steinmetz

³Public Research Centre for Health, Luxembourg

,

Yonghong Liao

¹Institute of Medicinal Plant Development, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, P. R. China

,

Ning Wang

³Public Research Centre for Health, Luxembourg

,

Bo Peng

²Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, P. R. China

,

Qi Chang

¹Institute of Medicinal Plant Development, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, P. R. China

› Author Affiliations

Abstract

3,6′-Disinapoylsucrose is a major active component of the herb Polygala tenuifolia which has long been used for relieving tranquilization, uneasiness of the mind, and improving learning and memory. Our previous study found that 3,6′-disinapoylsucrose had a very low oral bioavailability. Its mechanisms of absorption in the small intestine have so far been unclear. In the present study, the absorption mechanisms of 3,6′-disinapoylsucrose were investigated by using the Caco-2 cell monolayer and in situ rat intestinal perfusion models. The 3,6′-disinapoylsucrose concentration was determined by an LC/MS/MS method. In a Caco-2 cell transport study, the results showed that 3,6′-disinapoylsucrose had very limited intestinal permeability with average apparent permeability coefficient values around (1.11–1.34) × 10⁻⁷ cm/s from the apical (A) to the basolateral (B) side and (1.37–1.42) × 10⁻⁷ cm/s from B to A, at concentrations of 5, 20, and 33 µM. No concentration dependence in the 3,6′-disinapoylsucrose transport was observed. The apparent permeability coefficient value of 3,6′-disinapoylsucrose (5 µM) from A to B greatly increased to 4.49 × 10⁻⁷ and 1.81 × 10⁻⁷ cm/s, respectively, when the cells were preincubated with EDTA (17 mM) and sodium caprate (5.14 mM). No significant effect on the 3,6′-disinapoylsucrose transport by the inhibitors including verapamil, cyclosporine A, and sodium azide was observed. Similar results were found in the small intestinal perfusion study. The apparent permeability coefficient value of 3,6′-disinapoylsucrose greatly increased from 3.97 × 10⁻⁶ to 23.4 × 10⁻⁶ and 20.0 × 10⁻⁶ cm/s in the presence of EDTA (17 mM) and sodium caprate (5.14 mM), respectively, in perfusion buffer. An in vitro stability evaluation of 3,6′-disinapoylsucrose in the gastrointestinal tract showed that it was relatively stable both in the stomach and small intestine contents, while it was found to be more instable in the colon contents. All of the above results indicate that 3,6′-disinapoylsucrose might be transported across the intestinal mucosa by paracellular passive penetration and paracellular enhancers could increase the intestinal permeability of this compound and thus slightly improve its oral bioavailability.

Key words

3,6′-disinapoylsucrose - Polygala tenuifolia - Polygalaceae - Caco-2 cell - intestinal perfusion - absorption enhancer

Full Text

References

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