Rosa canina extract relieves methylation alterations of pancreatic genes in STZ-induced diabetic rats : Gene methylation in diabetic rats treated with an extract.

BACKGROUND: Diabetes is a chronic metabolic disease that affects many parts of the body. Considering diabetes as a beta cells' defect and loss, the focus is on finding mechanisms and compounds involved in stimulating the function and regeneration of pancreatic ß-cells. DNA methylation as an epigenetic mechanism plays a pivotal role in the ß-cells' function and development. Considering the regenerative and anti-diabetic effects of Rosa canina extract, this study aimed to assess the methylation levels of Pdx-1, Pax-4, and Ins-1 genes in diabetic rats treated with Rosa Canina extract. METHODS AND RESULTS: Streptozotocin-induced diabetic rats were used to evaluate the frequency of Pdx-1, Pax-4, and Ins-1 gene methylation. Treatment groups were exposed to Rosa canina as spray-dried and decoction extracts. Following blood glucose measurement, pancreatic DNA was extracted and bisulfited. Genes' methylation was measured using MSP-PCR and qRT-PCR techniques. Oral administration of Rosa canina extracts significantly reduced blood sugar levels in diabetic rats compared to the control group. The methylation levels of the Pdx-1, Pax-4, and Ins-1 genes promoter in streptozotocin-induced diabetic rats increased compared to the control rats while, the treatment of diabetic rats with Rosa canina extracts, spray-dried samples especially, led to a decreased methylation in these genes. CONCLUSION: The results of this study showed that Rosa canina extract as a spray-dried sample could be effective in treating diabetes by regulating the methylation of genes including Pdx-1, Pax-4, and Ins-1 involved in the activity and regeneration of pancreatic islet cells.

Modulation of Notch signaling and angiogenesis via an isolated polysaccharide from Momordica charantia in diabetic rats.

Given the impact of notch signaling in the modulation of metabolic diseases and normal tissue homeostasis, this study aimed to evaluate whether notch signaling has a role in anti-diabetic and islet regenerative effects of the isolated polysaccharide from Momordica charantia in diabetic rats. The polysaccharide was isolated from M. charantia (MCP) and was characterized by using FTIR and LC-MS/MS. The diabetic model was established by intraperitoneal administration of streptozotocin in male Wistar rats and grouped into control, diabetic, metformin (500 mg kg-1  day-1 ), and treatment (10 mg kg-1  day-1 ) groups. The levels of Hes1, Notch 1, DLL4, Jagged1, Pdx1, CD34, CD31, and VEGF were analyzed by using immunohistochemistry and real-time PCR. Structural analyses have revealed the polysaccharide structure of the isolated fraction. High blood glucose was normalized by MCP treatment in diabetic rats. MCP scaled up the mRNA levels of Ins1, jagged1, Pdx1, and Hes1 while it scaled down the levels of Notch1, Dll4, and the ratio of Bax/Bcl2 in diabetic rats. Furthermore, the immunohistochemistry staining levels of hes1, cyclin d1, and VEGF proteins were increased in the pancreas of MCP-treated diabetic rats compared to the diabetic group. These findings provide insights into the anti-diabetic potential of MCP through modulation of islets' regeneration and suggest that modulation of notch and angiogenesis pathways may play a pivotal role in the restoration of the islets to relieve diabetes. PRACTICAL APPLICATIONS: Polysaccharides extracted from Momordica charantia could normalize the level of blood glucose in STZ-induced type 2 diabetic rats through modulation of notch and angiogenesis singling pathways. Given that this effect was associated with the increased expression of Pdx-1 and Insulin in the pancreas, the isolated polysaccharide is expected to be introduced as a convenient medicine in the treatment of diabetes through modulation of ß-cell regeneration.

Antidiabetic potential of the isolated fractions from the plants of Rosaceae family in streptozotocin-induced diabetic rats.

BACKGROUND AND PURPOSE: Diabetes is a group of multifactorial disorders characterized by chronic-elevated blood glucose levels (hyperglycemia). Natural remedies are used as alternative medications to treat diabetes. Here, we tested the protective effect of the plant extracts of the Rosaceae family on improving insulin secretion and repairing the pancreatic beta cells in diabetic rats. EXPERIMENTAL APPROACH: The oligosaccharide fraction was isolated from the Rosaceae family of herbs. LC-MS/MS was applied to characterize the isolated fractions. The male Wistar rats were randomly divided into six groups, 10 each, including the control group with no intervention, diabetic rats without treatment, diabetic rats that received the extract of Malus domestica (apple), Cydonia oblonga (quince), Prunus persica (nectarine), and Prunus persica (peach), separately. Rats were monitored for the weight, fasting plasma glucose, and insulin levels. The effect of extracts in streptozotocin (STZ)-induced diabetic rats on the pancreatic islets was evaluated by morphometric analysis. FINDINGS/RESULTS: LC-MS/MS results indicated a similar mass spectrum of isolated fractions from nectarine and peach with Rosa canina. Oral administration of nectarine and peach extracts to STZ-induced diabetic rats showed restoration of blood glucose levels to normal levels with a concomitant increase in insulin levels. Morphometric analysis of pancreatic sections revealed the increase in number, diameter, volume, and area of the pancreatic islets in the diabetic rats treated with extracts compared to the untreated diabetic rats. CONCLUSION AND IMPLICATIONS: Nectarine and peach extracts' anti-diabetic properties improved insulin secretion and pancreatic beta-cell function and subsequently led to restoring pancreatic islet mass in STZ-induced diabetic rats.

Molecular mechanism of the anti-diabetic activity of an identified oligosaccharide from Rosa canina.

BACKGROUND AND PURPOSE: Because of the high prevalence, diabetes is considered a global health threat. Hence, the need for effective, cheap, and comfortable therapies are highly felt. In previous study, a novel oligosaccharide with strong anti-diabetic activity in the crude extract of Rosa canina fruits, from the rosacea family, was identified. The present study was designed to ensure its efficacy using in vivo and in vitro studies. EXPERIMENTAL APPROACH: Crude extract and its purified oligosaccharide were prepared from corresponding herb. Adult male Wistar rats were randomly divided into four groups of 10 each, as follows: group 1, healthy control rats given only sterile normal saline; group 2, diabetic control rats received sterile normal saline; group 3, diabetic rats treated with crude extract of Rosa canina (40% w/v) by oral gavage for 8 weeks; group 4, diabetic rats treated with purified oligosaccharide of Rosa canina (2 mg/kg) by oral gavage for 8 weeks. After treatment, body weight, fasting blood glucose, serum insulin levels and islet beta-cell repair and proliferation were investigated. The possible cytoprotective action of oligosaccharide was evaluated in vitro. The effect of oligosaccharide on apoptosis and insulin secretion in cell culture media were examined. Real-time PCR was used to determine the expression level of some glucose metabolism-related regulator genes. FINDINGS / RESULTS: In the animal model of diabetes, the insulin levels were increased significantly due to the regeneration of beta-cells in the islands of langerhans by the purified oligosaccharide. In vitro cell apoptosis examination showed that high concentration of oligosaccharide increased cell death, while at low concentration protected cells from streptozotocin-induced apoptosis. Molecular study showed that the expression of Ins1 and Pdx1 insulin production genes were increased, leading to increased expression of insulin-dependent genes such as Gck and Ptp1b. On the other hand, the expression of the Slc2a2 gene, which is related to the glucose transporter 2, was significantly reduced due to insulin concentrations. CONCLUSION AND IMPLICATIONS: The purified oligosaccharide from Rosa canina was a reliable anti-diabetic agent, which acted by increasing insulin production in beta-cells of the islands of Langerhans.