Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 47, Issue 3, Pages 604-614Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2012.04.018
Keywords
Diabetic cardiomyopathy; Curcumin; Protein kinase C; Mitogen-activated protein kinase
Categories
Funding
- Ministry of Education, Culture, Sports and Technology of Japan
- Promotion and Mutual Aid Corporation for Private Schools, Japan
Ask authors/readers for more resources
The development of diabetic cardiomyopathy is accompanied with a high membrane-bound protein kinase C (PKC) levels. Curcumin is a naturally occurring compound which is known to inhibit PKC activity. However, the effects of curcumin on ameliorating diabetic cardiomyopathy are still undefined. We evaluated whether curcumin treatment is associated with the modulation of PKC-alpha and -beta(2)-mitogen-activated protein kinase (MAPK) pathway in experimental diabetic cardiomyopathy. Diabetes was induced in male Sprague-Dawley rats by streptozotocin (STZ). Curcumin (100 mg/kg/day) was started three weeks after STZ injection and was given for 8 weeks. We demonstrate that curcumin significantly prevented diabetes-induced translocation of PKC-alpha and -beta 2 to membranous fraction and diabetes-induced increased phosphorylation of p38MAPK and extracellular regulated-signal kinase (ERK)1/2 in left ventricular tissues of diabetic rats. Curcumin treatment also markedly decreased NAD(P)H oxidase subunits (p67phox, p22phox, gp91phox), growth factors (transforming growth factor-beta, osteopontin) and myocyte enhancer factor-2 protein expression as well as inhibited NF-kappa B activity at nuclear level. Furthermore, curcumin decreased the mRNA expression of transcriptional coactivator p300 and atrial natriuretic peptide, decreased accumulation of ECM protein and reversed the increment of superoxide production in left ventricular tissues, as evidenced by dihydroethidium staining. It is also significantly lowered plasma glucose and attenuated oxidative stress, as determined by lipid peroxidation and activity of anti-oxidant enzyme, and as a result attenuated cardiomyocyte hypertrophy, myocardial fibrosis and left ventricular dysfunction. Taken together, it is suggested that curcumin by inhibiting PKC-alpha and -beta(2)-MAPK pathway may be useful as an adjuvant therapy for the prevention of diabetic cardiomyopathy. (C) 2012 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available