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Background: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Idebenone (IDE) has been proposed for the treatment of neurodegenerative diseases involving mitochondria dysfunctions. Unfortunately, to date, IDE therapeutic treatments have not been as successful as expected. To improve IDE efficacy, in this work we describe a two-step approach: (1) synthesis of IDE ester derivatives by covalent linking IDE to other two antioxidants, trolox (IDETRL) and lipoic acid (IDELIP), to obtain a synergic effect; (2) loading of IDE, IDETRL, or IDELIP into solid lipid nanoparticles (SLN) to improve IDE and its esters' water solubility while increasing and prolonging their antioxidant activity. IDE and its derivatives loaded SLN showed good physico-chemical and technological properties (spherical shape, mean particle sizes 23-25 nm, single peak in the size distribution, ζ potential values -1.76/-2.89 mV, and good stability at room temperature). In vitro antioxidant activity of these SLN was evaluated in comparison with free drugs by means of oxygen radical absorbance capacity (ORAC) test. IDETRL and IDELIP showed a greater antioxidant activity than IDE and encapsulation of IDE and its derivatives into SLN was able to prolong their antioxidant activity. These results suggest that loading IDETRL and IDELIP into SLN could be a useful strategy to improve IDE efficacy., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Background: Heme Oxygenase-1 (HO-1) is a metabolic enzyme strongly involved in processes including cytoprotection, modulation of inflammatory response, anti-oxidative functions, regulation of cellular proliferation, angiogenesis, cardiovascular homeostasis, and immuno-modulation. HO-1 induction and/or activation is able to counterbalance, at least in part, oxidative stress and inflammation. For this reason, HO-1 can be regarded as an attractive target to ameliorate different stress-related pathologies. Caffeic acid phenethyl ester, a natural polyphenolic compound, behaves as HO-1 inducer and possesses a plethora of beneficial effects under oxidative stress conditions., Objectives: A small focused series of caffeic acid phenethyl ester (Cape) analogues was designed and synthesized with the aim of obtaining more potent HO-1 inducers., Method: The capacity of these new compounds to modify the levels of HO-1 was evaluated in human mesenchymal stem cells (hMSCs) derived from bone marrow., Results and Conclusion: Some of tested compounds were found to be good HO-1 inducers and 3-(3,4- dihydroxyphenyl)-(2E)-2-propenoic acid 2-(3,4-dimethoxyphenyl) ethyl ester (VP961) was the most potent. VP961 tested to measure HO-1 protein expression and HO activity in in vitro system resulted more potent than the parent compound Cape both as inducer and as direct activator of the enzyme. VP961, selected as lead compound for further characterization, showed antioxidant properties in a model of H2O2-mediated ROS production and cytoprotective effects in a model of H2O2 cells viability impairment. To the best of our knowledge, VP961 is the first known compound able to activate directly HO-1 enzyme and to induce at the same time its protein expression., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Eggplant fruit is a very rich source of polyphenol compounds endowed with antioxidant properties. The aim of this study was to extract polyphenols from eggplant entire fruit, pulp, or skin, both fresh and dry, and compare results between conventional extraction and microwave-assisted extraction (MAE). The effects of time exposure (15, 30, 60, and 90 min) and solvent (water 100% or ethanol/water 50%) were also evaluated. The highest amount of polyphenols was found in the extract obtained from dry peeled skin treated with 50% aqueous ethanol, irradiated with microwave; this extract contained also high quantity of flavonoids and showed good antioxidant activity expressed by its capacity to scavenge superoxide anion and to inhibit lipid peroxidation.

We previously described a series of imidazole-based inhibitors substituted at N-1 with an arylethanone chain as interesting inhibitors of neuronal nitric oxide synthase (nNOS), endowed with good selectivity vs endothelial nitric oxide synthase (eNOS). As a follow up of these studies, several analogs characterized by the presence of substituted imidazoles or other mono or bicyclic nitrogen-containing heterocycles instead of simple imidazole were synthesized, and their biological evaluation as in vitro inhibitors of both nNOS and eNOS is described herein. Most of these compounds showed improved nNOS and eNOS inhibitory activity with respect to reference inhibitors. Selected compounds were also tested to analyze their antioxidant properties. Some of them displayed good capacity to scavenge free radicals and ability to reduce lipid peroxidation., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Eggplant fruit is a very rich source of polyphenol compounds endowed with antioxidant properties. The aim of this study was to extract polyphenols from eggplant entire fruit, pulp, or skin, both fresh and dry, and compare results between conventional extraction and microwave-assisted extraction (MAE). The effects of time exposure (15, 30, 60, and 90 min) and solvent (water 100% or ethanol/water 50%) were also evaluated. The highest amount of polyphenols was found in the extract obtained from dry peeled skin treated with 50% aqueous ethanol, irradiated with microwave; this extract contained also high quantity of flavonoids and showed good antioxidant activity expressed by its capacity to scavenge superoxide anion and to inhibit lipid peroxidation. [ABSTRACT FROM AUTHOR]