title: Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice.
abstract: BACKGROUND
  Caffeic acid (CA) and ellagic acid (EA) are phenolic acids naturally occurring in many plant foods. Cardiac protective effects of these compounds against dyslipidemia, hypercoagulability, oxidative stress and inflammation in diabetic mice were examined.
  
  
  METHODS
  Diabetic mice were divided into three groups (15 mice per group): diabetic mice with normal diet, 2% CA treatment, or 2% EA treatment. One group of non-diabetic mice with normal diet was used for comparison. After 12 weeks supplement, mice were sacrificed, and the variation of biomarkers for hypercoagulability, oxidative stress and inflammation in cardiac tissue of diabetic mice were measured.
  
  
  RESULTS
  The intake of CA or EA significantly increased cardiac content of these compounds, alleviated body weight loss, elevated plasma insulin and decreased plasma glucose levels in diabetic mice (p < 0.05). These treatments also significantly enhanced plasma antithrombin-III and protein C activities (p < 0.05); and decreased triglyceride content in cardiac tissue and plasma (p < 0.05), in which the hypolipidemic effects of EA were significantly greater than that of CA (p < 0.05). CA or EA significantly lowered cardiac levels of malondialdehyde, reactive oxygen species, interleukin (IL)-beta, IL-6, tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1 (p < 0.05); and retained cardiac activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (p < 0.05). These compounds also significantly up-regulated cardiac mRNA expression of GPX1, SOD and catalase; and down-regulated IL-1beta, IL-6, TNF-alpha and MCP-1 mRNA expression in diabetic mice (p < 0.05).
  
  
  CONCLUSIONS
  These results support that CA and EA could provide triglyceride-lowering, anti-coagulatory, anti-oxidative, and anti-inflammatory protection in cardiac tissue of diabetic mice. Thus, the supplement of these agents might be helpful for the prevention or attenuation of diabetic cardiomyopathy.
authors.affiliation: Department of Nutrition, China Medical University, Taichung City, Taiwan, Republic of China. cshc029@csh.org.tw
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Chao
authors.forename: Cheng-Chin
authors.initials: CC
authors.lastname: Hsu
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Yin
references.citation: Clin Chem. 1975 Mar;21(3):437-41
references.pmid: 1112059
references.citation: Photochem Photobiol. 2006 Nov-Dec;82(6):1668-76
references.pmid: 16836471
references.citation: Semin Thromb Hemost. 2000;26(1):39-42
references.pmid: 10805280
references.citation: Free Radic Biol Med. 1997;22(4):593-6
references.pmid: 9013122
references.citation: Anticancer Res. 2006 Sep-Oct;26(5A):3601-6
references.pmid: 17094489
references.citation: J Intern Med. 2001 Nov;250(5):415-21
references.pmid: 11887976
references.citation: Coron Artery Dis. 2005 Nov;16 Suppl 1:S3-S10
references.pmid: 16340402
references.citation: Cardiovasc Res. 2009 Feb 15;81(3):457-64
references.pmid: 19047340
references.citation: J Am Coll Cardiol. 2008 Aug 19;52(8):655-66
references.pmid: 18702970
references.citation: Hypertension. 2001 Apr;37(4):1053-9
references.pmid: 11304502
references.citation: Food Chem Toxicol. 2007 Oct;45(10):1899-909
references.pmid: 17560706
references.citation: J Lipid Res. 1973 May;14(3):364-6
references.pmid: 14580182
references.citation: Diabetes Res Clin Pract. 2000 Jul;49(1):23-31
references.pmid: 10808060
references.citation: Endocr Regul. 2008 Sep;42(4):129-35
references.pmid: 18999900
references.citation: Diabet Med. 2003 Nov;20(11):930-4
references.pmid: 14632719
references.citation: J Pharmacol Exp Ther. 2006 Aug;318(2):476-83
references.pmid: 16644902
references.citation: J Biol Chem. 2003 Nov 21;278(47):46654-60
references.pmid: 13129912
references.citation: Diabetes. 2004 May;53(5):1336-43
references.pmid: 15111504
references.citation: Eur J Clin Invest. 2000 Nov;30(11):995-1001
references.pmid: 11114962
references.citation: Thromb Haemost. 1997 Sep;78(3):1030-6
references.pmid: 9308749
references.citation: J Agric Food Chem. 2002 Jun 19;50(13):3660-7
references.pmid: 12059140
references.citation: Horm Metab Res. 2003 Apr;35(4):251-8
references.pmid: 12778369
references.citation: J Cardiovasc Pharmacol. 2008 Aug;52(2):136-44
references.pmid: 18670366
references.citation: Int J Food Sci Nutr. 2007 Feb;58(1):18-28
references.pmid: 17415953
references.citation: Food Chem Toxicol. 2008 Mar;46(3):1119-24
references.pmid: 18155344
references.citation: J Agric Food Chem. 2002 Apr 10;50(8):2432-8
references.pmid: 11929309
references.citation: Circ J. 2005 Dec;69(12):1484-9
references.pmid: 16308496
references.citation: Hypertension. 2003 Aug;42(2):206-12
references.pmid: 12847113
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713