Effects of Polyphenolic Derivatives on Heme Oxygenase-System in Metabolic Dysfunctions

The aim of this review is to summarize the effects of various naturally occurring polyphenols in the management of metabolic dysfunctions. This cluster of metabolic abnormalities comprises insulin resistance, increased levels of free fatty acids, hypercholesterolemia, obesity, hyperglycemia and hypertension, diabetes mellitus (DM) type 1 (T1DM) and type 2 (T2DM) along with DM-induced complications. Most of them are included in the well-known metabolic syndrome (MS). These metabolic dysfunctions in turn are tightly associated to a high risk of development of cardiovascular diseases. Although molecular mechanisms underlying the onset of metabolic dysfunctions and related complications are not yet clear, it is widely recognized that they are associated to oxidative stress and chronic low-grade of inflammatory levels.

We undertook a structured search of bibliographic references through the use of SciFinder. The database was provided by a division of ACS (American Chemical Society) and guarantees access to the world's most extensive and authoritative source of references. The search was performed using "heme oxygenase-1" as research topic and a subsequent refinement was done by using inclusion/exclusion criteria. The quality of retrieved papers was evaluated on the basis of standard tools.

From a careful review of the selected literature, of interest, the use of natural antioxidant polyphenols seems to be the ideal pharmacological treatment since they are endowed with strong antioxidant and anti-inflammatory properties. In particular, some polyphenols such as curcumin, quercetin, genistein, and caffeic acid phenethyl ester are able to potently activate nuclear factor erythroid 2-related factor 2 (Nrf2) and related downstream expression of enzymes such as heme oxygenase-1 (HO-1). Indeed, an overexpression of HO-1 has been demonstrated to play a beneficial role in metabolic diseases.

The following review is intended to stimulate interest in the role of natural occurring HO-1 inducers in metabolic dysfunction, focusing on the clinical potential of HO-1 activity to restore the balance between pro-oxidant and anti-oxidants systems.