Elucidation the mechanism of the active ingredient imperatorin promoting drug absorption in cell model

Author:

Ta Wenjing1,Wang Jie1,Song Jihong1,Li Xingyue1,Wang Jianxiang1,Lu Wen1ORCID

Affiliation:

1. School of Pharmacy, Health Science Center, Xi’an Jiaotong University , No. 76, Yanta West Road, Xi’an, 710061 , P.R. China

Abstract

Abstract Imperatorin (IMP) is the main bioactive furanocoumarin of Angelicae dahuricae radix, which is a well-known traditional Chinese medicine. The purpose of this study was to elucidate the role of IMP in promoting absorption and the possible mechanism on the compatible drugs of Angelicae dahuricae radix. The influence of IMP on drugs’ intestinal absorption was conducted by the Caco-2 cell model. The mechanism was studied by investigating the transcellular transport mode of IMP and its influence on P-glycoprotein (P-gp)-mediated efflux, protein expression of P-gp and tight junction, and cell membrane potential. The result showed IMP promoted the uptake of osthole, daidzein, ferulic acid, and puerarin and improved the transport of ferulic acid and puerarin in Caco-2 cells. The absorption-promoting mechanism of IMP might involve the reduction of the cell membrane potential, decrease of P-gp-mediated drug efflux and inhibition of the P-gp expression level in the cellular pathway, and the loosening of the tight junction protein by the downregulation of the expression levels of occludin and claudin-1 in the paracellular pathway. This study provides new insights into the understanding of the improved bioavailability of Angelicae dahuricae radix with its compatible drugs.

Funder

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

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