Anthocyanins as Protective Agents Against Metabolic Syndrome-Related Dysfunctions: Potential Mechanisms Underlying Preventive and Therapeutic Benefits

Metabolic syndrome (MetS) is the name for a group of risk factors which severely increases the risk of type II diabetes and cardiovascular diseases. Current evidence supported the potential of natural bioactive compounds to alleviate MetS components. Due to their multiple properties, anthocyanins (ACN), a class of polyphenolic compounds widely found in several mediterranean medicinal plants, provided evidence of protective effects in metabolic-related disorders contributing to vascular homeostasis, reducing hypertension, inflammation and platelet aggregation, and also improving insulin resistance and dyslipidaemia. Additionally, ACN can reduce fat accumulation in adipose tissue decreasing oxidative stress and inflammation and mitigating adipocytokine dysregulation. However, it is now considered that the in vivo beneficial effects of these phytochemicals are unlikely to be explained just by their antioxidant capability. Several plant antioxidants exhibit hormetic properties, by acting as “low-dose stressors” that may prepare cells to resist more severe stress. The discovery of specific genes regulated by Antioxidant Responsive Element – ARE (HO-1, NQO1, gGCS) and pathways (Nrf2 mediated adaptive response) affected by antioxidants, led to the hypothesis that ACN may act as modulators of gene regulatory and signal transduction pathways. Furthemore, ACN positively regulate glucose transporters density and function in both skeletal muscle and adipose tissues via the insulin signaling pathway and induce switching of the cells from an anabolic to a catabolic state through the upregulation of AMPK signaling. Here, the ACN-mediated protective effects against obesity, type 2 diabetes and vascular dysfunction will be discussed focusing on the underlying molecular mechanisms.