Antihyperglycemic Effects and Mode of Actions of Leaf and Fruit Peel Hydroethanolic Extracts in Nicotinamide/Streptozotocin-Induced Diabetic Rats.

The present study aimed to evaluate the antihyperglycemic effects of () leaf and fruit peel hydroethanolic extracts and to suggest their probable mode of actions in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic rats. The leaf and fruit peel hydroethanolic extracts were analyzed by GC-MS that indicated the presence of phytol, octadecatrienoic acid, hexadecanoic acid, and octadecadienoic acid as major components in the leaf extract and vitamin E, octadecenamide, -sitosterol, and stigmasterol as major phytochemicals in the fruit peel extract. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight) dissolved in citrate buffer (pH 4.5), 15 minutes after intraperitoneal injection of NA (120 mg/kg body weight). The NA/STZ-induced diabetic rats were, respectively, treated with . leaf and fruit peel hydroethanolic extracts at a dose of 100 mg/kg body weight/day by oral administration for 28 days. The treatment of NA/STZ-induced diabetic rats with leaf and fruit peel extracts significantly improved the impaired oral glucose tolerance and significantly increased the lowered serum insulin and C-peptide levels. The HOMA-IR (as the index of insulin resistance) and QUICKI (as a marker for insulin sensitivity), as well as HOMA- cell function were significantly alleviated as a result of treatment of diabetic rats with leaf and fruit peel extracts. In association, the elevated serum-free fatty acids, TNF-, and IL-6 levels were significantly decreased. In addition, the suppressed adipose tissue PPAR, GLUT4, adiponectin, and insulin receptor -subunit mRNA expressions were upregulated while the elevated adipose tissue resistin expression was downregulated in diabetic rats as a result of treatment with the leaf and peel extract. Based on these results, it can be concluded that leaf and fruit peel hydroethanolic extracts have antihyperglycemic effects which may be mediated via their insulinotropic and insulin-sensitizing effects.