Flavonoids and type 2 diabetes: Evidence of efficacy in clinical and animal studies and delivery strategies to enhance their therapeutic efficacy.

Diabetes mellitus type 2 (T2DM) is a metabolic disorder develops due to the overproduction of free radicals where oxidative stress could contribute it. Possible factors are defective insulin signals, glucose oxidation, and degradation of glycated proteins as well as alteration in glutathione metabolism which induced hyperglycemia. Previous studies revealed a link between T2DM with oxidative stress, inflammation and insulin resistance which are assumed to be regulated by numerous cellular networks such as NF-κB, PI3K/Akt, MAPK, GSK3 and PPARγ. Flavonoids are ubiquitously present in the nature and classified according to their chemical structures for example, flavonols, flavones, flavan-3-ols, anthocyanidins, flavanones, and isoflavones. Flavonoids indicate poor bioavailability which could be improved by employing various nano-delivery systems against the occurrences of T2DM. These bioactive compounds exert versatile anti-diabetic activities via modulating targeted cellular signaling networks, thereby, improving glucose metabolism, α -glycosidase, and glucose transport or aldose reductase by carbohydrate metabolic pathway in pancreatic β-cells, hepatocytes, adipocytes and skeletal myofibres. Moreover, anti-diabetic properties of flavonoids also encounter diabetic related complications. This review article has designed to shed light on the anti-diabetic potential of flavonoids, contribution of oxidative stress, evidence of efficacy in clinical, cellular and animal studies and nano-delivery approaches to enhance their therapeutic efficacy. This article might give some new insights for therapeutic intervention against T2DM in near future.