METHODS: In the Nrf2 induction study, mice were divided into control, 2000 mg/kg TRF and diethyl maleate treated groups. After acute treatment, mice were sacrificed at specific time points. Liver nuclear extracts were prepared and Nrf2 nuclear translocation was detected through Western blotting. To determine the effect of increasing doses of TRF on the extent of liver nuclear Nrf2 translocation and its implication on the expression levels of several Nrf2-regulated genes, mice were divided into 5 groups (control, 200, 500 and 1000 mg/kg TRF, and butylated hydroxyanisole-treated groups). After 14 days, mice were sacrificed and liver RNA was extracted for qPCR assay.
RESULTS: 2000 mg/kg TRF administration initiated Nrf2 nuclear translocation within 30 min, reached a maximum level of around 1 h and dropped to half-maximal levels by 24 h. Incremental doses of TRF resulted in dose-dependent increases in liver Nrf2 nuclear levels, along with concomitant dosedependent increases in the expressions of Nrf2-regulated genes.
CONCLUSION: TRF activated the liver Nrf2 pathway resulting in increased expression of Nrf2-regulated cytoprotective genes.
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.