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Berberine upregulates P-glycoprotein in human caco-2 cells and in an experimental model of colitis in the rat via activation of Nrf2-dependent mechanismss
Jing W.2,4; Safarpour Y.2; Zhang T.4; Guo P.3,4; Chen G.4; Wu X.1; Fu Q.4; Wang Y.3
2018
Source PublicationJournal of Pharmacology and Experimental Therapeutics
Volume366Issue:2Pages:332
Abstract

Downregulation of P-glycoprotein (P-gp) is implicated in the pathophysiology of inflammatory bowel disease (IBD). Berberine, a principal isoquinoline alkaloid extracted from Berberis species, has been reported to exhibit therapeutic potential in IBD. In this study, we used a dextran sulfate sodium (DSS)-induced colitis rat model to evaluate the effect of berberine on P-gp and explore its mechanism of action. Berberine treatment improved DSS-induced colitis symptoms, attenuated inflammatory markers (myeloperoxidase, tumor necrosis factor-a, and interleukin-1b and -6), and enhanced P-gp expression in a dose-dependent manner. Although colonic expression of the P-gp–related nuclear receptor pregnane X receptor and transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) were downregulated in the colitis model, gene and protein expression analysis revealed that berberine treatment reversed only the downregulation of Nrf2. In vitro studies using Caco-2 cells showed that the multidrug resistance 1 (MDR1) gene and P-gp protein were upregulated by berberine in a dose- and time-dependent manner. Significant upregulation of the MDR1 gene by berberine was abrogated by Nrf2 silencing, indicating that the Nrf2-mediated pathway was responsible for this activation. Luciferase assays showed a dose-dependent increase in Nrf2 reporter gene activity after berberine treatment in Caco-2 cells, with a significant 2-fold elevation at 2.5 mM berberine, suggesting that berberine is a strong Nrf2 activator. These results indicate the possible involvement of Nrf2-mediated upregulation of P-gp in the therapeutic effect of berberine on colitis and highlight the potential of P-gp and/or Nrf2 as new therapeutic targets for IBD. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics

DOI10.1124/jpet.118.249615
URLView the original
Language英语
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, China
2.School of Medicine, University of California, Irvine, CA, United States
3.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
4.School of Pharmacy, Xi’an Jiaotong University, Xi’an,, Shaanxi, China
Recommended Citation
GB/T 7714
Jing W.,Safarpour Y.,Zhang T.,et al. Berberine upregulates P-glycoprotein in human caco-2 cells and in an experimental model of colitis in the rat via activation of Nrf2-dependent mechanismss[J]. Journal of Pharmacology and Experimental Therapeutics,2018,366(2):332.
APA Jing W..,Safarpour Y..,Zhang T..,Guo P..,Chen G..,...&Wang Y..(2018).Berberine upregulates P-glycoprotein in human caco-2 cells and in an experimental model of colitis in the rat via activation of Nrf2-dependent mechanismss.Journal of Pharmacology and Experimental Therapeutics,366(2),332.
MLA Jing W.,et al."Berberine upregulates P-glycoprotein in human caco-2 cells and in an experimental model of colitis in the rat via activation of Nrf2-dependent mechanismss".Journal of Pharmacology and Experimental Therapeutics 366.2(2018):332.
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