الفهرس 
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Abstract
Diabetes mellitus (DM) represents one of the most common metabolic disorders worldwide. Diabetic vascular complications are the leading cause of end-stage renal failure, acquired blindness, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. This study aimed to assess the possible potential impacts of dimethylfumarate (DMF) and piperine (PIP) in streptozotocin (STZ)-induced diabetic associated vascular complications. Moreover, the possible underlying mechanisms of studied drugs were investigated. Type 1 DM was established after STZ injection in rats, which was evidenced by hyperglycemia (FBG > 250 mg/dL) and weight loss. Over 10 weeks of experimental diabetes, vascular complications were developed as demonstrated in glucose and lipid metabolism disturbance, increased AGE production, aortic oxidative stress, aortic inflammation, vascular dysfunction, and endothelial apoptosis. This study revealed the potential impacts of DMF and PIP treatment on diabetes associated vascular complications, where they successfully delayed its development possibly via their antioxidant, anti-inflammatory, hypolipidemic and hypoglycemic effect. Moreover, they restored vascular reactivity probably via upregulation of eNOS synthase expression, downregulation of iNOS expression and attenuation of endothelial apoptosis. Furthermore, DMF and PIP downregulated ROS-NLRP3 pathway through downregulation of TXNIP and NF-kB expression. The main findings of the current study showed that DMF and PIP exhibited potential vasculoprotective effects against diabetes-induced vascular dysfunction in rats, so both drugs might have bright prospects to be repurposed for future clinical use for reducing vascular complications of diabetes and subsequently may improve mortality and morbidity rate in diabetic patients.