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Depression: 21st Century Solutions + The Dark Side of Wheat

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Article Publish Status: FREE
Abstract Title:

Berberine upregulates P-glycoprotein in human Caco-2 cells and in an experimental model of colitis in the rat via activation of Nrf2-dependent mechanisms.

Abstract Source:

J Pharmacol Exp Ther. 2018 Jun 11. Epub 2018 Jun 11. PMID: 29891588

Abstract Author(s):

Wanghui Jing, Yasaman Safarpour, Ting Zhang, Pengqi Guo, Guoning Chen, Xiaoming Wu, Qiang Fu, Yitao Wang

Article Affiliation:

Wanghui Jing

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-α, and interleukin-1β 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 andprotein expression analysis revealed that berberine treatment only reversed 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 using Caco-2 cells showed a dose-dependent increase in Nrf2 reporter gene activity following berberine treatment, with a significant twofold elevation at 2.5 μM berberine, suggesting that berberine is a strong Nrf2 activator. These results suggest 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.

Study Type : Animal Study

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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