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Planta Med 2012; 78(7): 692-697
DOI: 10.1055/s-0031-1298368
Pharmacokinetic Investigations
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Intestinal Transport of Pure Diester-type Alkaloids from an Aconite Extract across the Caco-2 Cell Monolayer Model

Na Li1 , 2 , Rong Tsao3 , Zhigang Sui2 , Jingwei Ma1 , Zhiqiang Liu4 , Zhongying Liu1
  • 1College of Pharmacy, Jilin University, Changchun, China
  • 2Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
  • 3Guelph Food Research Centre, Agriculture and Agri-Food Canada, Guelph, Ontario, Canada
  • 4Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
Further Information

Publication History

received October 11, 2011 revised February 10, 2012

accepted February 16, 2012

Publication Date:
12 March 2012 (online)

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Abstract

Aconitine (AC), mesaconitine (MA), and hypaconitine (HA) are the active alkaloids identified in aconite tuber, an important traditional Chinese medicine. The study is aimed to investigate their intestinal transport profiles and potential interaction during the intestinal absorption using the Caco-2 cell monolayer model. All three alkaloids had good permeability with P app values greater than 1 × 10−6 cm · s−1. However, AC, MA, and HA in a mixture and as an extract, in both cases with the same content of alkaloids, showed higher transport efficiency in the apical to basolateral, and lower transport efficiency in the basolateral to apical directions. Digoxin, as a P-glycoprotein (P-gp) substrate, was substantially effluxed in the basolateral to apical direction but inhibited by the three alkaloids. Furthermore, the backwards transport of MA and HA was inhibited by the P-gp inhibitor verapamil. These observations indicated that the three alkaloids may not only be P-gp inhibitors but also its substrates; they interact with each other and can potentially enhance their own bioavailability when taken concomitantly.

Key words

Aconitum species - Ranunculaceae - Aconitum alkaloids - intestinal transport - Caco-2 cell monolayer - P-glycoprotein

Supporting Information

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Dr. Zhongying Liu

College of Pharmacy
Jilin University

1266 Fujin Road

Changchun 130021

China

Phone: +86 431 85 61 97 04

Fax: +86 431 85 26 22 36

Email: liuzy@jlu.edu.cn

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