The influence of rhein on the absorption of rehmaionoside D: In vivo, in situ, in vitro, and in silico studies

J Ethnopharmacol. 2022 Jan 10:282:114650. doi: 10.1016/j.jep.2021.114650. Epub 2021 Sep 16.

Abstract

Ethnopharmacological relevance: In traditional Chinese Medicine, Rehmannia glutinosa (Gaertn.) DC., as the principle herb of ShengDiHuang Decotion (SDHD), has the effect of cooling blood and hemostasis, and tonifying the yin and kidney. Rheum L., as adjuvant herbs, assist Rehmannia glutinosa (Gaertn.) DC. to promote blood circulation to remove blood stasis.

Aim of study: To study the mechanism of Rhein (RH) involved in the promotion of Rehmannioside D (RD) absorption by pharmacokinetic studies, single-pass intestinal perfusion, Caco-2 cell models, molecular docking technique and western blotting.

Materials and methods: Initially, the intestinal absorption of RD in the presence or absence of RH was conducted through pharmacokinetic studies. Thereafter, the intestinal absorption of RD and RH was studied using the single-pass intestinal perfusion and Caco-2 cell models. Finally, using molecular docking technique and western blotting.

Results: We found that the promotion of RD absorption by RH was mediated by breast cancer resistance and multidrug resistance-associated protein 2, thereby affecting the permeability of the intestinal epithelium. Additionally, RH and RD can competitively bind to breast cancer resistance and multidrug resistance-associated protein 2, and that RH inhibits the expression of breast cancer resistance and multidrug resistance-associated protein 2 in the ileum to promote the intestinal absorption of RD.

Conclusion: This study reveals the mechanisms associated with the RH-mediated promotion of RD absorption and provides a basis for further exploring the synergistic effect of Rehmannia glutinosa (Gaertn.) DC and rhubarb.

Keywords: Caco-2 cell model; Intestinal absorption; Pharmacokinetic; Rehmannioside D; Rhein.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / chemistry
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • Animals
  • Anthraquinones* / chemistry
  • Anthraquinones* / pharmacokinetics
  • Area Under Curve
  • Biological Transport
  • Caco-2 Cells
  • Cell Survival / drug effects
  • Computer Simulation
  • Drug Interactions
  • Gene Expression Regulation / drug effects
  • Half-Life
  • Humans
  • Male
  • Models, Molecular
  • Molecular Structure
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / metabolism
  • Protein Conformation
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • ABCG2 protein, human
  • Anthraquinones
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Neoplasm Proteins
  • rhein
  • rehmaionoside D