Green tea polyphenol epigallocatechin-3-gallate shows therapeutic antioxidative effects in a murine model of colitis.
OBJECTIVE
Leukocyte infiltration, up-regulation of proinflammatory cytokines and severe oxidative stress caused by increased amounts of reactive oxygen species are characteristics of inflammatory bowel disease. The catechin (2R,3R)-2-(3,4,5-Trihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol-3-(3,4,5-trihydroxybenzoate), named epigallocatechin-3-gallate, EGCG, has been demonstrated to exert anti-inflammatory and antioxidative properties, reducing reactive oxygen species in the inflamed tissues. The aim of this study was to evaluate the therapeutic effects of EGCG in a murine model of colitis induced by oral administration of dextran sodium sulfate.


METHODS
Mice received a daily oral administration of 6.9 mg/kg body weight EGCG or Piper nigrum (L.) alkaloid (2E,4E)-5-(1,3-benzodioxol-5-yl)-1-piperidin-1-ylpenta-2,4-dien-1-one, named piperine (2.9 mg/kg body weight) or the combination of the both - piperine was used in this combination to enhance the bioavailability of EGCG.


RESULTS
In vivo data revealed the combination of EGCG and piperine to significantly reduce the loss of body weight, improve the clinical course and increase overall survival in comparison to untreated groups. The attenuated colitis was associated with less histological damages to the colon and reduction of tissue concentrations of malondialdehyde, the final product of lipid peroxidation. Neutrophils accumulation indicator myeloperoxidase was found to be reduced in colon tissue, while antioxidant enzymes like superoxide dismutase and glutathione peroxidase showed an increased activity. In vitro, the treatment with EGCG plus piperine enhanced the expression of SOD as well as GPO and also reduced the production of proinflammatory cytokines.


CONCLUSIONS
These data support the concept of anti-inflammatory properties of EGCG being generally beneficial in the DSS-model of colitis, an effect that may be mediated by its strong antioxidative potential.
Department of Medicine B, Münster University Hospital, Albert-Schweitzer-Campus 1, Gebäude A1, D-48129 Münster, Germany. brueckner_markus@hotmail.com
Markus
M
Brückner
Sabine
S
Westphal
Wolfram
W
Domschke
Torsten
T
Kucharzik
Andreas
A
Lügering
D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D052117:Benzodioxoles / Q000494:pharmacology / Q000627:therapeutic use; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D005260:Female; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D053284:Polyunsaturated Alkamides / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
D000470:Alkaloids; D000975:Antioxidants; D052117:Benzodioxoles; D016209:Interleukin-8; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D002392:Catechin; D016264:Dextran Sulfate; C045651:epigallocatechin gallate; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C008922:piperine