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Nowadays, synthetic chemical antidiabetic drugs, besides their therapeutic effects, present adverse effects that could be hard to handle over time. In the last decade, studies reported new alternative molecules with more health benefits and less adverse effects. The goal of this study is to optimize a new antidiabetic formulation using plant flavonoids: Catechin, Epicatechin, and Rutin. They are also a powerful antioxidant and anti-inflammatory molecules. A mixture design experiment will optimize their combination to obtain a new, safe multi-targets antidiabetic formulation making it a powerful combination for the management of diabetes and its complications. To study the variation of blood glucose level in response to the treatment over the time we performed an Oral Glucose Tolerance Test. The blood glucose level variations recorded as responses for the mixture design experiment. We used the molecules at a dose of 10 mg/kg. According to the software analysis, the prediction profiler showed us the optimum combination, and the result was a binary combination between Rutin and Epicatechin (25% and 75%, respectively). This combination prevented hyperglycemia and hypoglycemia, along with the best area under the curve, and after that, we validated it through a repeated oral administration on alloxan-induced diabetic mice for 28 d. Rutin, Catechin, and Epicatechin exhibit a potent antihyperglycemic activity, their synergistic combination validates a new formulation that could be a real candidate to conventional drugs., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Coriandrum sativum L. seeds are traditionally used to treat diabetes and its complications (inflammation and formation of reactive oxygen species) around the world. The present study investigates the antidiabetic, anti-inflammatory, and antioxidant effects of the polyphenol fraction of Coriandrum sativum seeds (PCS). Diabetic mice were orally administered with PCS (25 and 50 mg/kg b.w.) for 28 days. Oral glucose tolerance (OGTT) was also evaluated along with the anti-inflammatory effect, assessed by measuring paw edema development induced with carrageenan in Wistar rat and the antioxidant activity assessed using two tests (β-carotene discoloration and DPPH). Treatment of diabetic mice with PCS for four weeks managed their high fasting blood glucose levels, improved their overall health, also revealed an excellent antihyperlipidemic activity. The OGTT result showed a potent antihyperglycemic activity, and following the anti-inflammatory and antioxidant effects, the PCS exhibited a perfect activity. LC-MS/MS result revealed the presence of 9 polyphenols. This modest work indicates that the PCS have an important antidiabetic, antihyperglycemic, antihyperlipidemic, anti-inflammatory, and antioxidant effect that can be well established treatment of diabetes and its complications.

Withania frutescens L. is a wild perennial woody plant used by the local population for diverse therapeutic purposes. This work aims to study for the first time the potential inhibitory effect of this plant hydroethanolic extract on α-amylase and α-glucosidase activities using in vitro methods and its antidiabetic and antihyperglycemic activities using alloxan-induced diabetic mice as a model for experimental diabetes. Two doses were selected for the in vivo study (200 and 400 mg/kg) and glibenclamide, a well-known antidiabetic drug (positive control) in a subacute study (28 days) where the antihyperglycemic activity was also assessed over a period of 12 h on diabetic mice. The continuous treatment of diabetic mice with the extract of Withania frutescens for 4 weeks succeeded to slowly manage their high fasting blood glucose levels (after two weeks), while the antihyperglycemic test result revealed that the extract of this plant did not control hyperglycemia in the short term. No toxicity signs or death were noted for the groups treated with the plant extract, and it shows a protective effect on the liver and kidney. The in vitro assays demonstrated that the inhibition of alpha-amylase and alpha-glucosidase might be one of the mechanisms of action exhibited by the extract of this plant to control and prevent postprandial hyperglycemia. This work indicates that W. frutescens have an important long term antidiabetic effect that can be well established to treat diabetes.

Background: Olea europea L. subsp. europaea var. sylvestris (Mill) Lehr (Oleaster) is a wild endemic olive tree indigenous to the Mediterranean region. Olea europea leaves represent a natural reservoir of bioactive molecules that can be used for therapeutic purposes., Aim of the Study: This work was conducted to study antidiabetic and antihyperglycemic activities of flavonoids from oleaster leaves using alloxan-induced diabetic mice. The mode of action of flavonoids against eight receptors that have a high impact on diabetes management and complication was also investigated using molecular docking., Results: During 28 days of mice treatment with doses 25 and 50 mg/kg b.w, the studied flavonoids managed a severe diabetic state (<450 mg/dL), exhibiting a spectacular antidiabetic and antihyperglycemic activity, and improved mice health status compared to diabetic control. The in-silico mode of action of oleaster flavonoids revealed the inhibition of protein tyrosine phosphatase 1B (PTP1B), Dipeptidyl-peptidase 4 (DPP4), α-Amylase (AAM), α-Glucosidase inhibition, Aldose reductase (AldR), Glycogen phosphorylase (GP), and the activation of free fatty acid receptor 1 (FFAR1)., Conclusion: The findings obtained in the present work indicate that the flavonoids from the oleaster may constitute a safe multi-target remedy to treat diabetes.