Abstract
BackgroundInsulin deficiency is the prime basis of all diabetic manifestations and agents that can bring about insulin secretion would be of pivotal significance for cure of diabetes. To test this hypothesis, we carried out bioactivity guided fractionation of Oreocnide integrifolia (Urticaceae); a folklore plant consumed for ameliorating diabetic symptoms using experimental models.MethodsWe carried out bioassay guided fractionation using RINmF and C2C12 cell line for glucose stimulated insulin secretion (GSIS) and glucose uptake potential of fractions. Further, the bioactive fraction was challenged for its GSIS in cultured mouse islets with basal (4.5 mM) and stimulated (16.7 mM) levels of glucose concentrations. The Flavonoid rich fraction (FRF) was exposed to 2 mM streptozotocin stress and the anti-ROS/RNS potential was evaluated. Additionally, the bioactive fraction was assessed for its antidiabetic and anti-apoptotic property in-vivo using multidose streptozotocin induced diabetes in BALB/c mice.ResultsThe results suggested FRF to be the most active fraction as assessed by GSIS in RINm5F cells and its ability for glucose uptake in C2C12 cells. FRF displayed significant potential in terms of increasing intracellular calcium and cAMP levels even in presence of a phosphodiesterase inhibitor, IBMX in cultured pancreatic islets. FRF depicted a dose-dependent reversal of all the cytotoxic manifestations except peroxynitrite and NO formation when subjected in-vitro along with STZ. Further scrutinization of FRF for its in-vivo antidiabetic property demonstrated improved glycemic indices and decreased pancreatic β-cell apoptosis.ConclusionsOverall, the flavonoid mixture has shown to have significant insulin secretogogue, insulinomimetic and cytoprotective effects and can be evaluated for clinical trials as a therapeutant in the management of diabetic manifestations.
Highlights
Insulin deficiency is the prime basis of all diabetic manifestations and agents that can bring about insulin secretion would be of pivotal significance for cure of diabetes
It is in this context that the World Health Organization (WHO) has encouraged and recommended the use of herbs as an alternative therapy for diabetes [6] and, though a wide range of medicinal plants are in use world over, many of them are with no valid scientific sanctity
glucose stimulated insulin secretion (GSIS) of various solvent extracts from RINm5F cell line Except for the ethyl acetate and methanol fractions, which showed a dose-dependent increase in insulin release, none of the other fractions showed any noticeable effect on insulin release under basal (4.5 mM glucose) glucose concentration (Figure 1)
Summary
Insulin deficiency is the prime basis of all diabetic manifestations and agents that can bring about insulin secretion would be of pivotal significance for cure of diabetes. Since the causes of diabetes are multifactorial and fraught with life threatening consequences; the disorder is in urgent need of a multimodal cost-effective therapeutic intervention that is more potent and sans side effects. It is in this context that the World Health Organization (WHO) has encouraged and recommended the use of herbs as an alternative therapy for diabetes [6] and, though a wide range of medicinal plants are in use world over, many of them are with no valid scientific sanctity. Plants/herbs constitute the main stay of health care system in rural areas due to limited access to modern health facilities
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