Scopoletin Supplementation Ameliorates Steatosis and Inflammation in Diabetic Mice

Phytotherapy Research - Tập 31 Số 11 - Trang 1795-1804 - 2017
Ra‐Yeong Choi1, Ju Ri Ham1, Hae-in Lee2, Hyun Wook Cho3, Myung‐Sook Choi4,5, Seok‐Kyu Park1, Jin Lee1, Myung‐Joo Kim6, Kwon‐Il Seo7, Mi‐Kyung Lee1
1Department of Food and Nutrition, Sunchon National University, Suncheon, 57922 Korea
2Mokpo Marin Food-Industry Research Center, Mokpo, 58621 Korea
3Department of Biology, Sunchon National University, Suncheon, 57922 Korea
4Center for Food and Nutritional Genomic Research, Kyungpook National University, Daegu, 41566 Korea
5Department of Food Science and Nutrition, Kyungpook National University, Daegu, 41566 Korea
6Department of Bakery and Barista, Suseong College, Daegu, 42078 Korea
7Department of Biotechnology, Dong-A University, Busan, 49315 Korea

Tóm tắt

Scopoletin is a bioactive component in many edible plants and fruits. This study investigated the effects of scopoletin on hepatic steatosis and inflammation in a high‐fat diet fed type 1 diabetic mice by comparison with metformin. Scopoletin (0.01%, w/w) or metformin (0.5%, w/w) was provided with a high‐fat diet to streptozotocin‐induced diabetic mice for 11 weeks. Both scopoletin and metformin lowered blood glucose and HbA1c, serum ALT, TNF‐α and IL‐6 levels, glucose intolerance, and hepatic lipid accumulation compared with the diabetic control group. Scopoletin or metformin down‐regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up‐regulated Cyp7a1 gene. Hepatic PPARγ and DGAT2 protein levels were also down‐regulated in scopoletin or metformin group compared with the control group. Scopoletin or metformin also inhibited hepatic fatty acid synthase and phosphatidate phosphohydrolase activities. These results suggest that scopoletin protects against diabetes‐induced steatosis and inflammation by inhibiting lipid biosynthesis and TLR4‐MyD88 pathways. Copyright © 2017 John Wiley & Sons, Ltd.

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Tài liệu tham khảo

10.1186/1471-2431-12-160

Anbu N, 2012, Anti‐diabetic activity of polyherbal formulation Aavaraiyathi churnam in alloxan induced diabetic rats, Int J Toxicol Pharmacol Res, 4, 77

Antunes C, 2017, StatPearls

10.1111/pedi.12337

10.1016/j.neuint.2016.01.001

10.1016/0003-2697(76)90527-3

10.1042/CS20110065

10.1016/j.ejphar.2010.06.043

Carvalho AL, 2017, High fat diet attenuates hyperglycemia, body composition changes, and bone loss in male streptozotocin‐induced type 1 diabetic mice, J Cell Physiol, 2017, 1

10.1074/jbc.M106219200

10.1172/JCI11245

10.3389/fendo.2017.00006

10.1074/jbc.M704213200

10.1007/BF00253736

10.3389/fmicb.2016.01186

10.1172/JCI23621

10.1161/01.CIR.0000034509.14906.AE

10.1016/j.foodchem.2015.08.129

10.1136/archdischild-2013-304237

10.1186/s12950-015-0080-5

10.1016/j.jff.2016.06.026

Hatanaka SA, 2015, Factors associated with elevated serum alanine aminotransferase in patients with type 1 diabetes mellitus, Minerva Gastroenterol Dietol, 61, 137

10.1089/jmf.2004.7.487

10.1093/oxfordjournals.jbchem.a021405

10.3402/fnr.v60.31304

10.1021/jf505975k

10.1073/pnas.1103451108

10.1002/hep.21752

10.1111/j.1365-313X.2008.03568.x

10.1016/j.fitote.2003.12.021

10.1002/hep.22109

10.1002/hep.20701

10.1016/j.toxlet.2015.06.016

10.1016/j.metabol.2014.01.003

10.1016/j.cell.2005.11.026

10.1210/jc.2010-1047

10.1006/meth.2001.1262

10.1002/3527608109.ch12

10.1016/j.phytochem.2011.11.009

10.1016/j.bbalip.2005.03.006

10.2337/diacare.25.12.2153

10.1111/j.1463-1326.2006.00599.x

10.1016/j.vph.2016.08.007

10.1074/jbc.M901488200

10.1016/j.phymed.2015.01.004

10.1194/jlr.M037812

10.1111/j.1472-8206.2009.00784.x

10.1155/2014/909586

10.1172/JCI34275

10.1016/j.lfs.2016.09.022

10.1900/RDS.2011.8.454

10.1074/jbc.273.34.22059

10.1002/ptr.1170

10.1007/s13197-014-1270-5

10.1002/hep.20919

10.1016/j.cell.2010.01.022

Verma A, 2013, Hypoglycemic and hypolipidemic activity of scopoletin (coumarin derivative) in streptozotocin induced diabetic rats, Int J Pharm Sci Rev Res, 22, 79

10.1007/s00125-009-1405-9

Yamamato M, 2010, Current views of toll‐like receptor signalling pathways, Gastroenterol Res Pract, 240, 240365

10.1074/jbc.M412989200

10.3389/fphys.2012.00138

10.1080/07853890510037383

10.1186/s12967-015-0529-6