Isoquercetin Improves Hepatic Lipid Accumulation by Activating AMPK Pathway and Suppressing TGF-β Signaling on an HFD-Induced Nonalcoholic Fatty Liver Disease Rat Model.

Abstract

Isoquercetin (IQ), a glucoside derivative of quercetin, has been reported to have beneficial effects in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the potential improvement of IQ in liver lipid accumulation, inflammation, oxidative condition, and activation in Kupffer cells (KCs) on a high-fat diet (HFD) induced NAFLD models. Male Sprague-Dawley (SD) rats were induced by HFD, lipopolysaccharides/free fatty acids (LPS/FFA) induced co-culture cells model between primary hepatocytes and Kupffer cells was used to test the effects and the underlying mechanism of IQ. Molecular docking was performed to predict the potential target of IQ. Significant effects of IQ were found on reduced lipid accumulation, inflammation, and oxidative stress. In addition, AMP-activated protein kinase (AMPK) pathway was activated by IQ, and is plays an important role in lipid regulation. Meanwhile, IQ reversed the increase of activated KCs which caused by lipid overload, and also suppression of Transforming growth factor beta (TGF-β) signaling by TGF-β Recptor-1 and SMAD2/3 signaling. Finally, TGF-βR1 and TGF-βR2 were both found may involve in the mechanism of IQ. IQ can improve hepatic lipid accumulation and decrease inflammation and oxidative stress by its activating AMPK pathway and suppressing TGF-β signaling to alleviate NAFLD.

• Authors: Guohong Qin, Ji Ma, Qiongshan Huang, Hongli Yin, Jichun Han, Maoru Li, Yang Deng, Bing Wang, Waseem Hassan, Jing Shang
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 19 Issue 12 (Dec 19 2018) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30572631 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Cytokines
• Transforming Growth Factor beta
• isoquercitrin
• Quercetin
• Protein Serine-Threonine Kinases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Biomarkers (blood)
• Coculture Techniques
• Cytokines (blood)
• Diet, High-Fat
• Disease Models, Animal
• Down-Regulation (drug effects)
• Inflammation (blood)
• Kupffer Cells (metabolism)
• Lipid Metabolism (drug effects)
• Liver (drug effects, metabolism)
• Male
• Molecular Docking Simulation
• Non-alcoholic Fatty Liver Disease (blood, drug therapy, metabolism)
• Oxidative Stress (drug effects)
• Phosphorylation (drug effects)
• Protein Serine-Threonine Kinases (metabolism)
• Quercetin (analogs & derivatives, pharmacology, therapeutic use)
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Transforming Growth Factor beta (metabolism)