Intervention Of Crocin On Vascular Injury In Experimental Diabetes

Background:Diabetes mellitus is a chronic metabolic diseases caused by either lack of insulin secretion or hyposensitivity to insulin, including metabolic disorder of carbohydrate, fat and protein, and is chiefly characterized by hyperglycemia. Diabetes mellitus usually associated with cardiovascular complications which are the principal cause of diabetic mortality, therefore it is of clinical importance to look for available drugs for their prevention and treatment. Lots of researchs have showed crocin exert many kinds of bioactivity, such as anti-hypertensive, anti-hyperlipidemia, anti-atherosclerosis and anti-oxidative stress. However, it remains unknown whether crocin have beneficial effects on diabetic vascular system. Objective:To explore the intervention effects of crocin on experimental diabetic vascular indury and its underlying mechanisms. Methods:Vascular protection of crocin for12weeks on experimental diabetic rat model induced by streptozotocin (60mg/kg, i.p.) was assayed. Effect of crocin on thoracic aortas perfused by high glucose (44mM,4h) or pyrogallol (500μM,10min) were measured. Moreover, biochemical indicator, such as reactive oxygen species (ROS) production, nitric oxide (NO) level, and superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and total nitric oxide synthase (tNOS) activity were detected. Results:Treatment with crocin (25,50,100mg/kg) for12 weeks did not reduce the blood glucose level in diabetic rats. Endothelium-dependent vasorelaxation of diabetic aortas were improved by crocin in dose dependent way, and these protective effects were cancelled by L-NAME and methylene blue, while SNP-induced vasorelaxation were not changed. In diabetic rat serum, treatment of crocin (100mg/kg) induced ROS production, enhanced SOD activity, improved NO level and tNOS activity, but not changed GSH-PX activity. Acute treatment with crocin (1,10,100μM) inhibited the impairment of endothelium-dependent vasorelaxation, which was cancelled by L-NAME and methylene blue, while didn’t impact SNP-induced vasorelaxation or basic tension in high glucose perfused aortas. The activities of SOD and tNOS in high glucose perfused aortas were enhanced by crocin (100μM). In pyrogallol-induced acute aorta injury model, crocin (1,10,100μM) markedly inhibited the impairment of endothelium-dependent vasorelaxation induced by pyrogallol, which was cancelled by L-NAME and methylene blue, but didn’t impact SNP-induced vasorelaxation. What’s more, treatment with crocin (100μM) also enhanced the activities of SOD and tNOS in pyrogallol perfused aortas. Conclusions: The results indicate that crocin might improve endothelium-dependent vasorelaxation in high glucose injured or diabetic aortas by enhancing SOD activity, reducing ROS production and activating aortic NOS-NO-sGC pathway.