Abstract
BackgroundCurcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. A novel water soluble curcumin derivative (NCD) has been developed to overcome low invivo bioavailability of curcumin. We evaluated the effect of the NCD on signaling mechanisms involved in cardiomyocyte hypertrophy and studied whether its action is mediated via inducible HO-1.Materials and methodsRats were divided into controls, controls receiving NCD, diabetic, diabetic receiving NCD, diabetic receiving pure curcumin, diabetic receiving HO inhibitor, zinc protoporphyrin IX (ZnPP IX) and diabetic receiving NCD and ZnPP IX. NCD and curcumin were given orally. After 45 days, cardiac physiologic parameters, plasma glucose, insulin, glycated hemoglobin (GHb), HO-1 gene expression and HO activity in pancreas and cardiac tissues were assessed. Gene expression of p300, atrial natriuretic peptide (ANP) and myocyte enhancer factor 2 (MEF2A and MEF2C) were studied.ResultsNCD and curcumin decreased plasma glucose, GHb and increased insulin levels significantly in diabetic rats. This action may be partially mediated by induction of HO-1 gene. HO-1 gene expression and HO activity were significantly increased in diabetic heart and pancreas. Diabetes upregulated the expression of ANP, MEF2A, MEF2C and p300. NCD and curcumin prevented diabetes-induced upregulation of these parameters and improved left ventricular function. The effect of the NCD was better than the same dose of curcumin.
Highlights
Curcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300
In diabetic rats receiving the novel water soluble curcumin derivative (NCD) or pure curcumin, left ventricular function was improved as indicated by increased heart rate, LVDP, LV dp/dt and decreased systolic blood pressure when compared with diabetic rats
Diabetic rats receiving pure curcumin showed no significant difference in left ventricular function compared with the diabetic group receiving the NCD
Summary
Curcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. Curcumin (turmeric) exhibits therapeutic actions in DM. Abdel Aziz et al [6] reported that insulin secretion, HO-1 gene expression and HO activity were significantly increased when rat isolated islets of Langerhans were incubated in curcumin. This increase in insulin secretion was significantly decreased by incubation of islets in the HO inhibitor, stannous mesoporphyrin (SnMP) suggesting that the action of curcumin on insulin secretion from isolated islets may be, in part, mediated through increased HO-1 gene expression
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