Efficacy of nobiletin, a citrus flavonoid, in the treatment of the cardiovascular dysfunction of diabetes in rats.
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.
Department of Pharmacology, SPP School of Pharmacy and Technology Management, NMIMS University, Vile Parle (W), Mumbai, 400056, India. addepalliv@gmail.com and Dr Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, 400056, India.
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Parkar
Dr Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, 400056, India.
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Bhatt
Department of Pharmacology, SPP School of Pharmacy and Technology Management, NMIMS University, Vile Parle (W), Mumbai, 400056, India. addepalliv@gmail.com.
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Addepalli
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D006332:Cardiomegaly / Q000188:drug therapy* / Q000209:etiology; D002957:Citrus / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy; D047309:Flavones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006439:Hemodynamics; D006943:Hyperglycemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D015415:Biomarkers; D047309:Flavones; D005419:Flavonoids; D010656:Phenylephrine; C008661:nobiletin; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D000109:Acetylcholine