Curcumin prevents diabetic cardiomyopathy in streptozotocin-induced diabetic rats: Possible involvement of PKC-MAPK signaling pathway

被引：132

作者：

Soetikno, Vivian ^{[1
,2
]}

Sari, Flori R. ^{[1
]}

Sukumaran, Vijayakumar ^{[1
]}

Lakshmanan, Arun Prasath ^{[1
]}

Mito, Sayaka ^{[1
]}

Harima, Meilei ^{[1
]}

Thandavarayan, Rajarajan A. ^{[1
]}

Suzuki, Kenji ^{[3
]}

Nagata, Masaki ^{[4
]}

Takagi, Ritsuo ^{[4
]}

Watanabe, Kenichi ^{[1
]}

机构：

[1] Niigata Univ Pharm & Appl Life Sci, Fac Pharmaceut Sci, Dept Clin Pharmacol, Niigata 9568603, Japan

[2] Univ Indonesia, Dept Pharmacol, Fac Med, Jakarta 10430, Indonesia

[3] Niigata Univ, Grad Sch Med & Dent Sci, Dept Gastroenterol & Hepatol, Niigata 9518510, Japan

[4] Niigata Univ, Grad Sch Med & Dent Sci, Dept Oral & Maxillofacial Surg, Niigata 9518510, Japan

来源：

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES | 2012年 / 47卷 / 03期

关键词：

Diabetic cardiomyopathy; Curcumin; Protein kinase C; Mitogen-activated protein kinase; PROTEIN-KINASE-C; SMOOTH-MUSCLE-CELLS; NF-KAPPA-B; OXYGEN SPECIES GENERATION; OXIDATIVE STRESS; HIGH GLUCOSE; SUPEROXIDE-PRODUCTION; FIBRONECTIN SYNTHESIS; CARDIAC-HYPERTROPHY; HUMAN NEUTROPHILS;

D O I：

10.1016/j.ejps.2012.04.018

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：604 / 614

页数：11

共 75 条

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