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Improvement of antihyperglycemic activity of nano-thymoquinone in rat model of type-2 diabetes.

Thymoquinone is a bioactive constituent of Nigella sativa seeds. It has been reported to possess antihyperglycemic effect in rats. However, the effect of nanoformulation (NF) of thymoquinone has not been reported in literature. So, the present study was designed with the aim to investigate the effect of nanoformulation of thymoquinone in streptozotocin-nicotinamide induced type-2 diabetic rats and compare its effect with pure bioactive compound as well as metformin, a standard antidiabetic drug. It is the first study reporting the use of thymoquinone NF against diabetes. Polymeric nanocapsules (NCs) of thymoquinone and metformin were prepared by nanoprecipitation method using gum rosin, a biocompatible polymer. Box-Behnken statistical analysis tool was used for the optimization of polymer and other excipients. The NCs were then characterized with respect to particle size, stability, morphology, and in vitro drug dissolution profiles. Furthermore, thymoquinone (20, 40 & 80 mg/kg), metformin (150 mg/kg) and their nanoformulations (20, 40 & 80 mg/kg for thymoquinone and 80 mg/kg for metformin) per se were administered for 21 successive days to type-2 diabetic rats. Body weight and blood glucose levels were measured every week for 3 weeks. Serum lipid profile and glycosylated hemoglobin were estimated on 22nd day. The nanocapsules were stable, spherical in shape and size was less than 100 nm. Thymoquinone-and metformin-loaded NCs showed sustained release profile as compared to their pure forms. Oral administration of thymoquinone, metformin and their nanoformulations significantly decreased blood glucose level and glycated haemoglobin; and improved the lipid profile of diabetic rats as compared to diabetic control rats. Thymoquinone-loaded NCs (containing 10, 20 and 40 mg of thymoquinone) produced dose-dependent antihyperglycemic effect and this effect was comparable to thymoquinone and metformin. In conclusion, thymoquinone nanocapsules (actually containing half of the doses of thymoquinone) produced better antihyperglycemic effect in type-2 diabetic rats as compared to thymoquinone alone.

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