METHODS: Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg) in to male Sprague-Dawley rats. Rats were divided into six different groups; normal control rats were not induced with STZ and served as reference, STZ diabetic control rats were given normal saline. Three groups were treated with OS aqueous extract at 0.2, 0.3 and 0.5 g/kg, orally twice daily continuously for 21 d. The fifth group was treated with glibenclamide (6 mg/kg) in aqueous solution orally continuously for 21 d. After completion of the treatment period, biochemical parameters and expression levels of glucose transporter 2 (Slc2a2), glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PCK1) were determined in liver by quantitative real time PCR.
RESULTS: Administration of OS at different doses to STZ induced diabetic rats, resulted in significant decrease (P<0.05) in blood glucose level in a dose dependent manner by 36%, 48%, and 64% at doses of 0.2, 0.3 and 0.5 g/kg, respectively, in comparison to the STZ control values. Treatment with OS elicited an increase in the expression level of Slc2a2 gene but reduced the expression of G6Pase and PCK1 genes. Morefore, OS treated rats, showed significantly lower levels of serum alanine transaminase (ALT), aspartate aminotransferase (AST) and urea levels compared to STZ untreated rats. The extract at different doses elicited signs of recovery in body weight gain when compared to STZ diabetic controls although food and water consumption were significantly lower in treated groups compared to STZ diabetic control group.
CONCLUSIONS: O. sumatrana aqueous extract is beneficial for improvement of hyperglycemia by increasing gene expression of liver Slc2a2 and reducing expression of G6Pase and PCK1 genes in streptozotocin-induced diabetic rats.
MATERIALS AND METHODS: Male and female Sprague-Dawley rats received three doses of mitragynine (1, 10, 100mg/kg, p.o) for 28 days respectively. Food intake and relative body weight were measured during the experiment. After completion of drug treatment biochemical, hematological, and histological analyses were performed.
RESULTS: No mortality was observed in any of the treatment groups. The groups of rats treated with the lower and intermediate doses showed no toxic effects during the study. However, the relative body weight of the group of female rats treated with the 100mg/kg dose was decreased significantly. Food intake also tended to decrease in the same group. Only relative liver weight increased after treatment with the high dose of mitragynine (100mg/ kg) in both the male and female treatment groups of rats. Biochemical and hematological parameters were also altered especially in high dose treatment group which corresponds to the histopathological changes.
CONCLUSIONS: The study demonstrated that mitragynine is relatively safe at lower sub-chronic doses (1-10mg/kg) but exhibited toxicity at a highest dose (sub-chronic 28 days: 100mg/kg). This was confirmed by liver, kidney, and brain histopathological changes, as well as hematological and biochemical changes.