4.7 Article

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

Journal

JOURNAL OF ETHNOPHARMACOLOGY
Volume 282, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2021.114650

Keywords

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

Funding

  1. Key Project of Science and Technology Department of Shaanxi Province [2018ZDXM-SF-002]
  2. Chinese Medicine Administration Project of Shaanxi Province [ZYPY010]
  3. Subject Innovation Team of Shaanxi University of Chinese Medicine [2019-YL11]
  4. Scientific Research Project of Affiliated Hospital of Shaanxi University of Chinese Medicine [2020MS017]

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This study investigated the mechanism of Rhein in promoting the absorption of Rehmannioside D, revealing that it acts by affecting the permeability of the intestinal epithelium and competitively binding with relevant proteins. This provides a basis for further exploring the synergistic effect of Rehmannia glutinosa and rhubarb.
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) ab-sorption 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.

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