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

• Published in: Food & function 2016-07, Vol.7 (7), p.3121-3129
• Main Authors: Parkar, N. A, Bhatt, L. K, Addepalli, V
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Animals; Antioxidants - pharmacology; Biomarkers - blood; Cardiomegaly - drug therapy; Cardiomegaly - etiology; Citrus; Citrus - chemistry; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Flavones - pharmacology; Flavonoids - pharmacology; Hemodynamics; Hyperglycemia - blood; Hyperglycemia - complications; Hyperglycemia - drug therapy; Male; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Oxidative Stress - drug effects; Phenylephrine - pharmacology; Rats; Rats, Wistar
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/c6fo00294c

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. Nobiletin, due to its MMP-2 & MMP-9 inhibitory and antioxidant effects, may ameliorate the cardiovascular dysfunction of diabetes.