Standardized extract of Ficus deltoidea stimulates insulin secretion and blocks hepatic glucose production by regulating the expression of glucose-metabolic genes in streptozitocin-induced diabetic rats

Abstract

BackgroundRecently, there has been increasing interest in Ficus deltoidea Jack. (Moraceae) due to its chemical composition and the potential health benefits. The present study was undertaken to investigate the effect of extracts of F. deltoidea leaves on diabetes.MethodsThe petroleum ether, chloroform and methanol extracts of F. deltoidea were prepared and subjected to standardization using preliminary phytochemical and HPLC analysis. Dose selection was made on the basis of acute oral toxicity study (50–5000 mg/kg b. w.) as per OECD guidelines. Diabetes mellitus was induced with streptozotocin and rats found diabetic were orally administered with the extract (250, 500 and 1000 mg/kg) for 14 days. Levels of blood glucose and insulin were measured in control as well as diabetic rats on 0, 7 and 14th day. In addition, glucose metabolism regulating gene expression was assessed using RT-PCR.ResultsHPLC analysis revealed that the methanol extract is enriched with C-glycosylflavones particularly, vitexin and isovitexin. In oral glucose tolerance test, oral administration of the methanol extract increased the glucose tolerance. The methanol extract showed significant (P < 0.01) antidiabetic activity. The extract treatment caused significant reduction (p < 0.01) in elevated fasting blood glucose level in streptozotocin-induced diabetic rats. The streptozotocin-related weight loss in rats was noticeably reversed by the extract treatment. Finally, RT-PCR analysis revealed a novel mechanisms for the anti-diabetic action of methanol extract of F. deltoidea. The extract exerted its effect via an increase of insulin secretion which impeded the hepatic glucose production, via down-regulation of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase genes expression on one hand, and up-regulation of hepatic GK and PPARγ genes expression on the other hand. The extract caused an increased expression of GLUT-4 gene expression in skeletal muscles which leads to normalize the hyperglycemia. The extract also nullified the toxic effects of streptozitocin by blocking its entry into the islet β-cells through reducing the expression of GLUT-2 gene.ConclusionIt can be concluded that, F. deltoidea could potentially inhibits the streptozitocin-induced hyperglycemia in rats. Further the herb can be utilized as useful remedy for alleviation of diabetes complications.

Ficus deltoideaextract down-regulates protein tyrosine phosphatase 1B expression in a rat model of type 2 diabetes mellitus: a new insight into its antidiabetic mechanism

“…In the present study, diabetic rats showed up-regulation of mRNA expression of the rate-limiting gluconeogenic enzymes, G6Pase and PEPCK (Figs 9(B) and (C)). These results are consistent with Farsi et al and Xia et al (13,94) . As selective enhancement of insulin signalling in the liver would suppress gluconeogenesis, FD-induced improvement in insulin signalling was expected to inhibit the expression of gluconeogenesis-related genes.…”

“…These findings could be attributed to stimulation of basal and insulin-mediated glucose uptake into adipocytes and liver cells due to the insulin-mimic activity of FD (9,11,60) . Moreover, Farsi et al (13) stated that the bioactive flavone C-glycosides, vitexin and isovitexin contents of FD are efficient antioxidants, and play a crucial role in cytoprotection and scavenging of free radicals, thereby protecting the β-cells from oxidative damage, and subsequently exerting antidiabetic activity. Additionally, FD stimulates insulin secretion due to its content of water-soluble insulin-secreting compounds and its involvement in the K + -ATP-dependent pathway.…”

Inhibition of the hepatic glucose output is responsible for the hypoglycemic effect of Crataegus aronia against type 2 diabetes mellitus in rats

“…The procedure was optimized for semiquantitative detection using primer pairs and conditions described in Supplementary Table S2 and previously used by Farsi et al [27]. Total RNA was extracted from frozen liver parts (30 mg) using an RNeasy Mini Kit (Qiagen Pty.…”

Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in the Quest for the Molecules With Therapeutic and Preventive Potential

“…The methanol extract of Ficus deltoidea leaves, which is also enriched in both compounds, displayed major antidiabetic effects when administered to SZT‐induced diabetic rats, including plasma glucose reduction, increased insulin secretion, and reduced gluconeogenesis through the inhibition of PEPCK and G6Pase hepatic enzymes. Furthermore, it enhanced the expression of GLUT‐4 glucose transporters in skeletal muscles . However, the potency of these compounds is divergent and seemingly dependent upon the glycosylation pattern: in fact, when tested separately in sucrose‐loaded induced diabetic mice, isovitexin significantly reduced postprandial glucose levels when administered orally at 20 mg/kg, while vitexin required a higher dose (50 mg/kg) to achieve a similar effect.…”