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

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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/