Minimization of the Risk of Diabetic Microangiopathy in Rats by Nigella sativa

BACKGROUND: Microangiopathy is a chronic diabetic complication resulting from metabolic derangements, oxidative stress, and increased pro-inflammatory cytokine production. Nigella sativa Linn. is used as an herbal medicine that exerts hypoglycemic, antilipidemic, anti-inflammatory, and antioxidant effects. OBJECTIVE: To examine the effects of N. sativa extract on cutaneous microvascular changes in diabetic rats. MATERIALS AND METHODS: Sprague-Dawley rats were randomly assigned into the following four groups: Untreated and N. sativa-treated normal controls and untreated and N. sativa-treated rats with streptozotocin-induced diabetes. A cold-pressed N. sativa extract was then orally administered (1000 mg/kg/day). After 8 weeks of treatment, the glucose, glycosylated hemoglobin (HbA(1c)), tumor necrosis factor-alpha (TNF-α), insulin levels, and lipid profile were determined in cardiac blood. Dermal capillary wall thickness was measured in tail skin sections stained with periodic acid-Schiff. Endothelial apoptosis was morphologically evaluated by hematoxylin and eosin staining. RESULTS: Diabetes significantly reduced the circulating insulin and low-density lipoprotein levels and caused elevations in the glucose, HbA(1c), and triglyceride levels, accompanied by a slight increase in total cholesterol levels and no change in the high-density lipoprotein and TNF-α levels. Capillary basement membrane thickening and a decreased capillary luminal diameter despite no evidence of endothelial cell apoptosis were also observed. N. sativa treatment of diabetic rats reduced the mean HbA(1c) concentration by 1.4%, enlarged the capillary lumens, and tended to attenuate dermal capillary basement membrane thickening without affecting the lipid profile or TNF-α level. CONCLUSION: Our results indicate that N. sativa may be used to minimize the risk of diabetic microangiopathy, potentially due in part to its glycemic control activity. SUMMARY: Diabetes causes dermal capillary basement membrane thickening and a decreased capillary luminal diameter. Nigella sativa treatment of diabetic rats enlarged the capillary lumens and tended to attenuate dermal capillary basement membrane thickening. N. sativa treatment of diabetic rats reduced the mean glycosylated hemoglobin concentration by 1.4%, which exceeds the necessary reduction previously described to decrease the risk of diabetic microangiopathy, without affecting the lipid profile or tumor necrosis factor-alpha level. N. sativa improves rat diabetic microangiopathy, potentially due in part to its glycemic control activity. Abbreviations used: H and E: Hematoxylin and eosin, HbA1c: Glycosylated hemoglobin, HDL-C: High-density lipoprotein cholesterol, LDL-C: Low-density lipoprotein cholesterol, PAS: Periodic acid-Schiff, STZ: Streptozotocin,