Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review

Abstract

Polyphenolic compounds are thought to show considerable promise for the treatment of various metabolic disorders, including type 2 diabetes mellitus (T2DM). This review addresses evidence from in vitro, in vivo, and clinical studies for the antidiabetic effects of certain polyphenolic compounds. We focus on the role of cytotoxic human amylin (hA) aggregates in the pathogenesis of T2DM, and how polyphenols can ameliorate this process by suppressing or modifying their formation. Small, soluble amylin oligomers elicit cytotoxicity in pancreatic islet β-cells and may thus cause β-cell disruption in T2DM. Amylin oligomers may also contribute to oxidative stress and inflammation that lead to the triggering of β-cell apoptosis. Polyphenols may exert antidiabetic effects via their ability to inhibit hA aggregation, and to modulate oxidative stress, inflammation, and other pathways that are β-cell-protective or insulin-sensitizing. There is evidence that their ability to inhibit and destabilize self-assembly by hA requires aromatic molecular structures that bind to misfolding monomers or oligomers, coupled with adjacent hydroxyl groups present on single phenyl rings. Thus, these multifunctional compounds have the potential to be effective against the pleiotropic mechanisms of T2DM. However, substantial further research will be required before it can be determined whether a polyphenol-based molecular entity can be used as a therapeutic for type 2 diabetes.

Supplementation with a Cocoa–Carob Blend, Alone or in Combination with Metformin, Attenuates Diabetic Cardiomyopathy, Cardiac Oxidative Stress and Inflammation in Zucker Diabetic Rats

“…Chronic supplementation with CCB significantly ameliorated fasting and postprandial hyperglycaemia, glucose intolerance and insulin resistance in diabetic animals and these effects were similar to those obtained just with metformin, used as a reference. These results agree with previous reports showing the potential antidiabetic effects of cocoa [ 16 , 17 ] and carob [ 22 , 23 , 24 ] and support the relevance of flavonoid rich-diets for controlling metabolic disorders such as diabetes [ 29 ]. Indeed, foods rich in flavonoids contain many bioactive compounds with multiple targets, which can exert synergistic effects, and, therefore, have the potential to be effective in restoring the multiple molecular pathways altered in T2D [ 13 ].…”

Hepatic AMPK activation in response to dynamic REDOX balance is a biomarker of exercise to improve blood glucose control

“…The remission of diabetes by antioxidant intervention has been well documented. Some compounds in food that have a vigorous antioxidant activity or inhibit NADPH oxidase, such as polyphenols and flavonoids ( 37 ), have been confirmed to improve blood glucose and relieve type 2 diabetes in animal experiments. Several clinical trials also demonstrated the relief of antioxidants in diabetic hyperglycaemia ( 38, 39 ).…”

Computational Methods for the Interaction between Cyclodextrins and Natural Compounds: Technology, Benefits, Limitations, and Trends

“…In addition to improving the above-mentioned activities of natural compounds, the inclusion with CDs can also improve the anti-inflammatory, antiviral, antidiabetic, and other activities of natural compounds. The biological activities of these compounds all involve receptor–ligand interactions, − thus the corresponding mechanisms may be complicated. Similarly, appropriate computational methods can be used to simulate binding conformations, key forces, and modes of interaction to explain the mechanism of action of these compounds.…”