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Mol Pharm. 2018 Aug 6;15(8):3272-3284. doi: 10.1021/acs.molpharmaceut.8b00332. Epub 2018 Jul 13.

Metformin Protects against LPS-Induced Intestinal Barrier Dysfunction by Activating AMPK Pathway.

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1
College of Animal Science, Zhejiang University, Key Laboratory of Animal Nutrition & Feed Sciences, Ministry of Agriculture , Zhejiang Provincial Laboratory of Feed and Animal Nutrition , No. 866 Yuhangtang Road , Hangzhou , Zhejiang 310058 , P. R. China.

Abstract

Metformin not only regulates energy metabolism but also participates in many cellular processes. In this study, we investigated the effect of metformin on lipopolysaccharide (LPS)-induced intestinal barrier damage. We found that LPS treatment decreased the expression of tight junction proteins and caused a proinflammatory response and oxidative stress in the intestine. Interestingly, metformin treatments attenuated LPS-induced intestinal barrier damage, inflammation, and oxidative stress. We found that metformin improved the expression of intestinal tight junction proteins (ZO1, occludin, and Claudin1) that were reduced by LPS stimulation. Moreover, metformin alleviated LPS-induced NF-κB phosphorylation, promoted Nrf2 nuclear translocation, and increased the expression of the antioxidative genes (HO-1 and NQO-1), leading to reduced intestinal ROS content. Mechanistically, we found that metformin protects against LPS-induced intestinal barrier dysfunction by activating AMPK. These results reveal the potential of metformin as an effective therapy for treating intestinal diseases.

KEYWORDS:

AMPK; intestinal barrier; intestinal inflammation; metformin; oxidative stress

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