Screening study of the antihyperglycemic action of new solid quercetin dispersions

The aim – to screen new solid dispersions of quercetin for the presence of antihyperglycemic action and to identify the most active substances that are promising for the creation of antidiabetic drugs. Materials and methods. The object of the study was 4 new solid dispersions of quercetin, developed at the National University of Pharmacy. Solid dispersions of quercetin were prepared by the liquid-phase method; hydroxypropyl methylcellulose (HPMC) or polyvinylpyrrolidone (PVP) in ratios of 1:1 and 1:2 were used as a carrier. The antihyperglycemic effect of the studied substances at a dose of 50 mg / kg was assessed in rats by the ability to lower blood glucose levels after carbohydrate loading in a model of impaired glucose tolerance induced by dexamethasone and in experimental type 2 diabetes mellitus induced by dexamethasone. Results. It was found that with impaired glucose tolerance, a solid dispersion of quercetin with HPMC (1:1) showed a pronounced antihyperglycemic effect – the glucose level 30 minutes after glucose load significantly decreased by 28 % and did not differ from the action of metformin, which was confirmed by the value of the area under glycemic crooked. When solid dispersions with PVP (1:1 and 1:2) were used, the antihyperglycemic effect was less pronounced. In a model of type 2 diabetes mellitus, a significant antihyperglycemic effect was found only in a solid dispersion of quercetin with HPMC (1:1) at the metformin level, which indicates an increase in the solubility and absorption of quercetin. Conclusions. A pronounced antihyperglycemic effect at the metformin level was found in a solid dispersion of quercetin with HPMC in a 1:1 ratio with impaired glucose tolerance and type 2 diabetes mellitus. It has been proven that a solid dispersion of quercetin with HPMC is a promising substance for creating a monocomponent drug or for inclusion in a new antidiabetic combined drug

Antihyperglycemic Effect of Lavandula pedunculata: In Vivo, In Vitro and Ex Vivo Approaches

Lavandula pedunculata (Mill.) Cav. (LP) is one of lavender species traditionally used in Morocco to prevent or cure diabetes, alone or in the form of polyherbal preparations (PHP). Therefore, the primary objective of this study was to test the antihyperglycemic effect of the aqueous extract of LP, alone and in combination with Punica granatum L. (PG) and Trigonella foenum-graecum L. (FGK). The secondary objective was to explore some mechanisms of action on the digestive functions. The antihyperglycemic effect of the aqueous extract of LP, alone and in combination with PG and FGK, was studied in vivo using an oral glucose tolerance test (OGTT). In addition, LP extract was tested on the activities of some digestive enzymes (pancreatic α-amylase and intestinal α-glucosidase) in vitro and on the intestinal absorption of glucose ex vivo using a short-circuit current (Isc) technique. Acute and chronic oral administration of LP aqueous extract reduced the peak of the glucose concentration (30 min, p < 0.01) and the area under the curve (AUC, p < 0.01). The effect of LP + PG was at the same amplitude to that of the positive control Metformin (MET). LP aqueous extract inhibited the pancreatic α-amylase with an IC50 almost identical to acarbose (0.44 ± 0.05 mg/mL and 0.36 ± 0.02 mg/mL, respectively), as well as the intestinal α-glucosidase, (IC50 = 131 ± 20 µg/mL) and the intestinal glucose absorption (IC50 = 81.28 ± 4.01 µg/mL) in concentration-dependent manners. LP aqueous extract exhibited potent actions on hyperglycemia, with an inhibition on digestive enzymes and glucose absorption. In addition, the combination with PG and FGK enhanced oral glucose tolerance in rats. These findings back up the traditional use of LP in type 2 diabetes treatment and the effectiveness of the alternative and combinative poly-phytotherapy (ACPP).

Beneficial Effect of Saharan Propolis on Glucose Metabolism in Streptozotocin-induced Diabetic Rats

Aims: The aim of the study was to evaluate the antihyperglycemic activity of propolis from Saharan region of Morocco. Background: Propolis is known from ancient times for its beneficial action on health. Objective: The study aimed to evaluate the effect of Moroccan propolis aqueous extract from the desert region on glycemia and lipid metabolism. Methods: The antihyperglycemic and antidyslipidemic activities of Moroccan propolis aqueous extract were evaluated in streptozotocin-induced diabetic rats. Glycemia was monitored during acute (6h) and subchronic treatments. Histopathological analysis of the liver and the serum lipid profile was also evaluated in addition to the glucose tolerance. Results: This work demonstrated that the aqueous extract of Moroccan propolis exhibited a significant antihyperglycemic effect in diabetic rats. Histopathological data demonstrated that propolis acts positively on the liver of diabetic rats. In addition, the preliminary phytochemical screening revealed that Moroccan propolis contains several phytochemicals. Finally, Moroccan propolis had a potent antioxidant activity which may be due to the richness in polyphenols content (90.91 mg EAG/1 g of extract). Conclusion: The present study shows that Moroccan propolis from the hot desert region possesses a potent antihyperglycemic effect.

Identification of a discrete neuronal circuit that relays insulin signaling into the brain to regulate glucose homeostasis

26RFa (QRFP) is a biologically active peptide that regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity at the periphery. 26RFa is also produced by a neuronal population localized in the hypothalamus. In the present study, we have investigated whether the 26RFa neurons may be involved in the hypothalamic regulation of glucose homeostasis. Our data indicate that 26RFa, i.c.v. injected, induces a robust antihyperglycemic effect associated with an increase of insulin production by the pancreatic islets. In addition, we found that insulin strongly stimulates 26RFa expression and secretion by the hypothalamus. RNAscope experiments revealed that neurons expressing 26RFa in the lateral hypothalamic area and the ventromedial hypothalamic nucleus also express the insulin receptor and that insulin induces the expression of 26RFa in these neurons. Concurrently, we show that the central antihyperglycemic effect of insulin is abolished in presence of a 26RFa receptor (GPR103) antagonist as well as in mice deficient for 26RFa. Finally, our data indicate that the hypothalamic 26RFa neurons are not involved in the central inhibitory effect of insulin on hepatic glucose production, but mediate the central effects of the hormone on its own peripheral production. To conclude, in the present study we have identified a novel actor of the hypothalamic regulation of glucose homeostasis, the 26RFa/GPR103 system and we provide the evidence that this neuronal peptidergic system is a key relay for the central regulation of glucose metabolism by insulin.

Opuntia dillenii (Ker Gawl.) Haw., Seeds Oil Antidiabetic Potential Using In Vivo, In Vitro, In Situ, and Ex Vivo Approaches to Reveal Its Underlying Mechanism of Action

Opuntia dillenii Ker Gawl. is one of the medicinal plants used for the prevention and treatment of diabetes mellitus (DM) in Morocco. This study aims to investigate the antihyperglycemic effect of Opuntia dillenii seed oil (ODSO), its mechanism of action, and any hypoglycemic risk and toxic effects. The antihyperglycemic effect was assessed using the OGTT test in normal and streptozotocin (STZ)-diabetic rats. The mechanisms of action were explored by studying the effect of ODSO on the intestinal absorption of d-glucose using the intestinal in situ single-pass perfusion technique. An Ussing chamber was used to explore the effects of ODSO on intestinal sodium-glucose cotransporter 1 (SGLT1). Additionally, ODSO’s effect on carbohydrate degrading enzymes, pancreatic α-amylase, and intestinal α-glucosidase was evaluated in vitro and in vivo using STZ-diabetic rats. The acute toxicity test on mice was performed, along with a single-dose hypoglycemic effect test. The results showed that ODSO significantly attenuated the postprandial hyperglycemia in normal and STZ-diabetic rats. Indeed, ODSO significantly decreased the intestinal d-glucose absorption in situ. The ex vivo test (Ussing chamber) showed that the ODSO significantly blocks the SGLT1 (IC50 = 60.24 µg/mL). Moreover, ODSO indu\ced a significant inhibition of intestinal α-glucosidase (IC50 = 278 ± 0.01 µg/mL) and pancreatic α-amylase (IC50 = 0.81 ± 0.09 mg/mL) in vitro. A significant decrease of postprandial hyperglycemia was observed in sucrose/starch-loaded normal and STZ-diabetic ODSO-treated rats. On the other hand, ODSO had no risk of hypoglycemia on the basal glucose levels in normal rats. Therefore, no toxic effect was observed in ODSO-treated mice up to 7 mL/kg. The results of this study suggest that ODSO could be suitable as an antidiabetic functional food.