Pharmacokinetic incompatibility of the Huanglian-Gancao herb pair

BMC Complement Med Ther. 2020 Feb 22;20(1):61. doi: 10.1186/s12906-020-2845-5.

Abstract

Background: Pharmacokinetic interaction is one of the most important indices for the evaluation of the compatibility of herbal medicines. Both Gancao (Glycyrrhizae Radix et Rhizoma) and Huanglian (Coptidis Rhizoma) are commonly used traditional Chinese medicines (TCMs). In this study, the influence of Gancao on the pharmacokinetics of Huanglian was systematically studied by using berberine as a pharmacokinetic marker.

Methods: Extracts of the herbal pieces of Huanglian and the herb pair (Huanglian plus Gancao) were prepared with boiling water. The concentration of berberine in the samples was analyzed using liquid chromatography-mass spectrometry. The total amounts of berberine in all extract samples were compared. Comparative pharmacokinetic studies of Huanglian and the herb pair were conducted in ICR mice. In vitro berberine absorption and efflux were studied using mice gut sacs. The equilibrium solubility of berberine in the extracts was determined. The in vitro dissolution of berberine was comparatively studied using a rotating basket method.

Results: Gancao significantly reduced berberine exposure in the portal circulation (425.8 ng·h/mL vs. 270.4 ng·h/mL) and the liver (29,500.8 ng·h/mL vs. 15,422.4 ng·h/mL) of the mice. In addition, Gancao decreased the peak concentration (Cmax) of berberine in the portal circulation (104.3 ng·h/mL vs. 76.5 ng·h/mL) and liver (4926.1 ng·h/mL vs. 2642.8 ng·h/mL) of mice. Significant influences of Gancao on the amount of berberine extracted (32% reduction), the solubility of berberine (34.7% compared with the control group), and dissolution (88.7% vs. 66.1% at 15 min in acid buffer and 68% vs. 51.8% at 15 min in phosphate buffer) were also revealed. Comparative pharmacokinetic studies in ICR mice indicated that the formation of sediment was unfavorable in terms of berberine absorption (345.3 ng·h/mL vs. 119.8 ng·h/mL).

Conclusions: Gancao was able to reduce intestinal absorption and in vivo exposure of berberine in Huanglian via the formation of sediment, which caused reductions in the extracted amount, solubility, and dissolution of berberine.

Keywords: Experimental design; Gancao; Herb pair; Herb-herb interaction; Huanglian; Pharmacokinetic interaction.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Berberine / pharmacokinetics*
  • Chromatography, Liquid
  • Drug Therapy, Combination
  • Drugs, Chinese Herbal / pharmacokinetics*
  • Female
  • Glycyrrhiza
  • Male
  • Mass Spectrometry
  • Medicine, Chinese Traditional
  • Mice, Inbred ICR
  • Plant Extracts / pharmacokinetics*
  • Plant Roots

Substances

  • Drugs, Chinese Herbal
  • Plant Extracts
  • huanglian
  • Berberine
  • glycyrrhizae radix et rhizoma