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Curcumin Regulates Expression and Activity of Matrix Metalloproteinases 9 and 2 during Prevention and Healing of Indomethacin-induced Gastric Ulcer

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Curcumin Regulates Expression and Activity of Matrix Metalloproteinases 9 and 2 during Prevention and Healing of Indomethacin-induced Gastric Ulcer
 
Creator Swarnakar, Snehasikta
Ganguly, Krishnendu
Kundu, Parag
Banerjee, Aditi
Maity, Pallab
Sharma, Anamika V.
 
Subject Drug Development/Diagnostics & Biotechnology
 
Description Matrix metalloproteinases (MMPs) are suggested to play a critical role in extracellular matrix degradation and remodeling during inflammation and wound healing processes. However, the role of MMPs in indomethacin- induced gastric ulcer and its healing process are not clearly understood. This study is aimed at determining the regulation of MMP-9 and -2 activities in indomethacin- induced acute gastric ulceration and healing. Indomethacin- ulcerated stomach extracts exhibit significant up-regulation of pro-MMP-9 (92 kDa) activity and moderate reduction of MMP-2 activity, which strongly correlate with indomethacin dose and severity of ulcer. The anti-inflammatory and antioxidant properties of curcumin, an active component of turmeric, suggest that curcumin may exert antiulcer activity through scavenging reactive oxygen species, by regulating MMP activity, or both. To test these possibilities, the effect of curcumin in indomethacin-induced gastric ulcer is examined by biochemical and histological methods. The results show that curcumin exhibits potent antiulcer activity in acute ulcer in rat model by preventing glutathione depletion, lipid peroxidation, and protein oxidation. Denudation of epithelial cells during damage of gastric lumen is reversed by curcumin through re-epithelialization. Furthermore, both oral and intraperitoneal administration of curcumin blocks gastric ulceration in a dose-dependent manner. It accelerates the healing process and protects gastric ulcer through attenuation of MMP-9 activity and amelioration of MMP-2 activity. Omeprazole, an established antiulcer drug does not inhibit MMP-9 while protecting indomethacin-induced gastric ulcer. We conclude that antiulcer activity of curcumin is primarily attributed to MMP-9 inhibition, one of the major pathways of ulcer healing.
 
Publisher American Society for Biochemistry and Molecular Biology
 
Date 2005
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/512/1/JOURNAL_OF_BIOLOGICAL_CHEMISTRY_280_(10_9409%2D9415;2005[84].pdf
Swarnakar, Snehasikta and Ganguly, Krishnendu and Kundu, Parag and Banerjee, Aditi and Maity, Pallab and Sharma, Anamika V. (2005) Curcumin Regulates Expression and Activity of Matrix Metalloproteinases 9 and 2 during Prevention and Healing of Indomethacin-induced Gastric Ulcer. The Journal of Biological Chemistry, 280 (10). pp. 9409-9415.
 
Relation Http://dx.doi.org/10.1074/jbc.M413398200
http://www.eprints.iicb.res.in/512/