Efficacy of nobiletin, a citrus flavonoid, in the treatment of the cardiovascular dysfunction of diabetes in rats

Food & Function Pub Date: 2016-05-26 DOI: 10.1039/C6FO00294C

Abstract

Hyperglycemia induced oxidative stress is a prime factor for cardiovascular dysfunction (CVD) in diabetic patients. In this process matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) play important roles. Nobiletin, a polymethoxy citrus flavone, has potent MMP-2 and MMP-9 inhibitory activity in addition to antioxidant activity. We hypothesized that nobiletin due to its MMP-2 & MMP-9 inhibitory and antioxidant effects may ameliorate the cardiovascular dysfunction of diabetes. Diabetes was induced using streptozotocin (50 mg kg?1 i.p.) in male wistar rats. Four weeks after the induction of diabetes, the rats were treated with nobiletin (10 mg kg?1, and 25 mg kg?1) for a period of the following four weeks. At the end of eight weeks, hemodynamic parameters were recorded, cardiac hypertrophy was measured, and antioxidant assays, and gelatin zymography for MMP-2 & MMP-9 analysis and histopathology were performed. The vascular reactivity of the aorta was measured by recording the contractile response to phenylephrine and relaxation responses to acetylcholine. Treatment with 25 mg kg?1 nobiletin ameliorated the hemodynamic parameters, oxidative stress, collagen level, MMP-2 and MMP-9 levels, and vascular reactivity significantly compared with vehicle treated diabetic group. Thus, this study suggests that nobiletin ameliorates the CVD of diabetes by inhibiting oxidative stress, MMP-2 & MMP-9 and can be used as a potential therapeutic approach.

Graphical abstract: Efficacy of nobiletin, a citrus flavonoid, in the treatment of the cardiovascular dysfunction of diabetes in rats
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