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

Abstract Ethnopharmacological relevance In traditional Chinese Medicine, Rehmannia glutinosa (Gaertn.) DC., as the principle herb of ShengDiHuang Decotion, 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 involved in the promotion of Rehmannioside D 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 Rehmannioside D in the presence or absence of Rhein was conducted through pharmacokinetic studies. Thereafter, the intestinal absorption of Rehmannioside D and Rhein 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 Rehmannioside D absorption by Rhein was mediated by breast cancer resistance and multidrug resistance-associated protein 2, thereby affecting the permeability of the intestinal epithelium. Additionally, Rhein and Rehmannioside D can competitively bind to breast cancer resistance and multidrug resistance-associated protein 2, and that Rhein inhibits the expression of breast cancer resistance and multidrug resistance-associated protein 2 in the ileum to promote the intestinal absorption of Rehmannioside D. Conclusion This study reveals the mechanisms associated with the Rhein-mediated promotion of Rehmannioside D absorption and provides a basis for further exploring the synergistic effect of Rehmannia glutinosa (Gaertn.) DC and rhubarb.