Integrated pharmacokinetics and biodistribution of multiple flavonoid C-glycosides components in rat after oral administration of Abrus mollis extract and correlations with bio-effects

J Ethnopharmacol. 2015 Apr 2:163:290-6. doi: 10.1016/j.jep.2014.12.067. Epub 2015 Jan 19.

Abstract

Ethnopharmacological relevance: Abrus mollis, a commonly used traditional Chinese medicine in China and other Asia countries, has been used clinically to prevent and treat hepatitis and alcoholic liver disease for decades.

Materials and methods: A modified HPLC-MS method was developed for the determination of vicenin-2 (AM-I), isoschaftoside (AM-II), and schaftoside (AM-III) of AM extract (AME) in rat plasma and tissues (heart, liver, spleen, lungs, and kidneys). Following oral administration of AME to rat at a dose of 200mg/kg, the concentrations of AM-I, II and III in plasma and tissues were quantified. An integrated double peak pharmacokinetics model was used to fit the concentration-time curves. The effects of drug on the bile flow and toe swelling of rats induced by carrageenan were also studied.

Results: The limit of quantitation of this modified HPLC-MS method decreased from 25 to 5ng/mL for plasma and from 100 to 10ng/g for tissue. These concentration-time curves show two successive maximum concentrations. The results of integrated double peak pharmacokinetics in this paper indicated that the three flavonoid C-glycosides may be absorbed by two sites of intestine in vivo. These results of bile flow and toe swelling showed a significant correlation between the pharmacokinetics and pharmacodynamics.

Conclusions: The novel integrated double peak pharmacokinetic approach to studying the holistic pharmacokinetic properties of traditional Chinese medicine has been successfully developed and validated using AM as a model drug. This study would be a useful guide for the holistic double peak pharmacokinetic study in consistence with the intrinsic theory and characteristics of traditional Chinese medicine.

Keywords: Abrus mollis; Correlation between pharmacokinetics and bio-effect; Double peak curve; Flavonoid C-glycosides; Integrated pharmacokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abrus*
  • Administration, Oral
  • Animals
  • Apigenin / blood
  • Apigenin / metabolism*
  • Carrageenan
  • Chromatography, High Pressure Liquid
  • Edema / chemically induced
  • Edema / drug therapy
  • Glucosides / blood
  • Glucosides / metabolism*
  • Glycosides / blood
  • Glycosides / metabolism*
  • Kidney / metabolism
  • Liver / metabolism
  • Lung / metabolism
  • Male
  • Mass Spectrometry
  • Myocardium / metabolism
  • Plant Components, Aerial
  • Plant Extracts / pharmacokinetics*
  • Plant Extracts / therapeutic use
  • Rats, Sprague-Dawley
  • Spleen / metabolism
  • Tissue Distribution

Substances

  • Glucosides
  • Glycosides
  • Plant Extracts
  • apigenin-6,8-di-C-glycopyranoside
  • schaftoside
  • Apigenin
  • Carrageenan
  • isoschaftoside