RESUMO
BACKGROUND: Diabetes mellitus is a metabolic disorder associated with relative or absolute insulin deficiency or resistance, characterized by hyperglycemia. Modern prescriptions such as pioglitazone have better therapeutic potential, but its side effects and financial burden for developing countries have motivated the researchers to find alternative natural drugs to compete hyperglycemia in patients with diabetes. The present study was conducted to explore the therapeutic potential of selected medicinal plants for the treatment of diabetes as an alternative to allopathic medicines. METHOD: In present study, hydroalcoholic extracts of Curcuma longa, Lavandula stoechas, Aegle marmelos, and Glycyrrhiza glabra and their polyherbal preparation (PHP) as compound drug were investigated for their antihyperglycemic potential in alloxan-induced diabetic mice. The study subjects (mice) were divided into different groups as normal control, diabetic control, pioglitazone treated (standard drug), test groups (plant extract treated 50, 100, and 150 mg/kg body weight), and PHP-treated group. Blood glucose concentration of all the study animals was determined by Glucose strip test. Qualitative phytochemical analysis of all the plant extracts was also performed following standard methods. RESULT: It was investigated that treatment of alloxan-induced diabetic mice with hydroalcoholic extracts of studied medicinal plants showed significant (P < .05) effects on fasting blood glucose levels (from baseline to normal range) in a manner comparable to that of the reference drug, pioglitazone (1 mg/kg body weight intraperitoneal). The tested plant extracts significantly (P < .05) reduced the glucose concentration in blood of diabetes-induced mice in a dose-dependent manner. CONCLUSION: It could be concluded that studied medicinal plants have antihyperglycemic activity. The study findings favor the use of traditional herbal medicinal practices for the management of diabetes that might due to the presence of bioactive phytoconstituents in plants. However, larger studies are required to identify, isolate, and characterize the bioactive phytoconstituents responsible for antihyperglycemic activity of studied medicinal plants.
RESUMO
Protein tyrosine phosphatase predominantly determines the status of protein tyrosine kinase-dependent phosphorylation of specific proteins and controls the survival and death of neurons. Previous studies have shown that protein tyrosine phosphatase activity is decreased during hypoxia in cortical membranes of the newborn piglet. We have also shown that nitric oxide (NO) free radicals are generated during hypoxia, and may result in modification of protein tyrosine phosphatase via peroxynitrite-mediated modification. The present study tests the hypothesis that the hypoxia-induced decrease in protein tyrosine phosphatase activity is NO-mediated. To test this hypothesis, in vitro experiments were conducted by measuring protein tyrosine phosphatase activity in the presence of an NO donor, sodium nitroprusside (SNP), or peroxynitrite. Since 3-nitrotyrosine is produced as a consequence of peroxynitrite reactions, we have also examined the effect of 3-nitrotyrosine on protein phophatase activity. Cerebral cortical P(2) membranes were prepared from seven normoxic newborn piglets and each sample was divided into three aliquots: a control group, a SNP group (exposed to 200 microM SNP), and a peroxynitrite group (exposed to 100 microM peroxynitrite). Protein tyrosine phosphatase activity was determined spectrophotometrically in the presence or absence of 2 microM bpV(phen), a highly selective inhibitor of protein tyrosine phosphatase. The protein tyrosine phosphatase activity was 198+/-25 nmol/mg protein/h in the normoxic group, 177+/-30 nmol/mg protein/h in the SNP group (p=NS versus normoxic) and 77+/-20 nmol/mg protein/h in the peroxynitrite group (p<0.001 versus normoxic). The results show that peroxynitrite but not SNP exposure results in decreased protein tyrosine phosphatase activity in vitro. Furthermore 3-nitrotyrosine (100 microm), a product of peroxynitrite, decreased the enzyme activity from 926+/-102 to 200+/-77 (p<0.001). We conclude that protein tyrosine phosphatase regulation is mediated by peroxynitrite. We propose that hypoxia-induced NO production leading to peroxynitrite formation is a potential mechanism of protein tyrosine phosphatase inactivation in vivo. The NO-induced decrease in protein tyrosine phosphatase and protein phosphatase activity, leading to Bcl-2 protein phosphorylation and loss of its antiapoptotic activity may be a NO-mediated mechanism of programmed cell death in the hypoxic brain.