Abstract 18398: Amelioration of Cardiovascular Dysfunction by Nobiletin in Diabetic Rats
Introduction: Strategies that interrupt the Matrix Metalloproteinase-2 (MMP-2) and Matrix Metalloproteinase-9 (MMP-9) system have been shown to reduce the ensuing threatening risk factors of cardiovascular complications of diabetes by alteration in Extracellular Matrix
Hypothesis: We hypothesized that interruption of MMP-2 and 9 can reduce cardiovascular dysfunction of diabetes. Objective of this study was to investigate efficacy of Nobiletin in treatment of cardiovascular dysfunction of diabetes. Nobiletin is a citrus flavonoid with MMP-2 and MMP-9 inhibitory activity.
Methods: Diabetes was induced by Streptozotocin (55 mg/kg i.p.) in wistar male rats. Four week after the induction of diabetes rats were treated with Nobiletin (25 mg/kg, and 50 mg/kg) for a period of three weeks. At the end of eight week hemodynamic parameters like arterial pressure, heart rate and left ventricular pressure were recorded. Contractile response to phenylephrine (10-5 M) and relaxation responses to acetylcholine (10-9 to 10-4 M) were obtained from aortic rings of diabetic rats. Cardiac hypertrophy was measured and histopathology was done using Masson’s Trichrome stain method. Gel zymography was performed to evaluate MMP-2 and MMP-9 levels.
Results: Diabetes resulted in significant reduction in heart rate, mean arterial pressure, + dp/dtmax and -dp/dtmax (223 ± 26, 83 ± 9 mmHg, 2673 ± 323 and -2035 ± 216 mmHg/s respectively) when compared with normoglycemic group (285 ± 26, 102 ± 8 mmHg, 3546 ± 324 and -3132 ± 235 mmHg/s respectively). Treatment with 50 mg/kg Nobiletin significantly ameliorated these parameters (254 ± 27, 98 ± 9, 3175 ± 357 and - 2932 ± 243 mmHg/s respectively) compared to vehicle treated diabetic group. Endothelium-dependent relaxation responses induced by acetylcholine were decreased in diabetic rats (% relaxation 56.3 ± 1.83) and significantly higher in combination treated group (% relaxation 31.3 ± 2.31). When compared with diabetic control group, collagen, MMP-2 and MMP-9 levels were significantly decreased in combined treated group.
Conclusion: Results of the present study suggest that Nobiletin attenuate cardiovascular dysfunction in diabetic rats by inhibition of MMP-2 & MMP-9 and can be a potential non glycaemic approach for the treatment.
- © 2013 by American Heart Association, Inc.