The purpose of this review is to discuss the recent developments related to the chemistry and medicinal properties of flavonoids. Major flavonoids that show well categorized structures and well defined structure function-relationships are: flavans, flavanones, flavones, flavanonols, flavonols, catechins, anthocyanidins and isoflavone. The biological properties of flavonoids include antioxidant, anti-inflamatory, antitumoral, antiviral and antibacterial, as well as a direct cytoprotective effect on coronary and vascular systems, the pancreas and the liver. These characteristics place them among the most attractive natural substances available to enrich the current therapy options.

The purpose of this review is to discuss the cellular and molecular mechanisms of action of flavonoids focusing on carbohydrate metabolism. The beneficial effects of flavonoids have been studied in relation to diabetes mellitus, either through their capacity to avoid glucose absorption or to improve glucose tolerance. Furthermore, flavonoids stimulate glucose uptake in peripheral tissues, regulate the activity and/or expression of the rate-limiting enzymes in the carbohydrate metabolism pathway and act per se as insulin secretagogues or insulin mimetics, probably, by influencing the pleiotropic mechanisms of insulin signaling, to ameliorate the diabetes status.

A stimulatory effect of kaempferol 3-neohesperidoside ( 1) on glucose uptake (35% and 21%) was observed when the rat soleus muscle was incubated with 1 and 100 nM of this flavonoid glycoside, respectively. The concentration-response curve of insulin showed a stimulatory effect at 3.5 and 7.0 nM (42% and 50%) on glucose uptake when compared with the control group. The effect of 1 on glucose uptake was completely nullified by pretreatment with LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), and RO318220, an inhibitor of protein kinase C (PKC). However, no significant change occurred on glucose uptake stimulated by 1 when muscles were pretreated with PD98059, an inhibitor of mitogen-activated protein kinase (MEK), and cycloheximide, an inhibitor of protein synthesis. Compound 1 and insulin (7 nM) did not show a synergistic effect on glucose uptake. Additionally, 100 mg/kg of 1 by oral gavage was able to increase glycogen content in the muscle. These results suggest that 1 stimulates glucose uptake in the rat soleus muscle via the PI3K and PKC pathways and, at least in part, independently of MEK pathways and the synthesis of new glucose transporters.

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