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Diabetes mellitus is a complex metabolic disease characterized by high blood sugar levels. Different pathogenic processes are involved in the etiology of the disease. Indeed, chronic diabetes hyperglycemia is often associated with severe long-term complications including cardiovascular symptoms, retinopathy, nephropathy, and neuropathy. Although the precise molecular mechanisms underlying diabetes are not yet clear, it is widely accepted that increased levels of oxidative stress are involved in the onset, development and progression of diabetes and its related complications. In this regard, the use of natural antioxidant polyphenols, able to control free radical production, to increase intracellular antioxidant defense and to prevent the onset of oxidative stress, can be of high interest. Caffeic acid phenethyl ester (CAPE), a natural polyphenolic substance, is one of the main components of propolis. Due to its multifaceted biological activities, including antioxidant, antimicrobial, anti-inflammatory, antitumor, and immunomodulatory effects, CAPE has received great attention during the last few decades. In the present paper the therapeutic potential of CAPE in diabetes is extensively reviewed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.)

Sulla coronaria is indigenous to the Mediterranean region. It is grown as fodder in southern Italy because it contains various secondary metabolites with beneficial activities on animals. Recently, its potential use in cosmeceutical treatments for skin problems was reported. In this scenario, to contribute to a possible cosmeceutical application, we characterized the phytochemical profile of Sulla coronaria flowers' hydroalcoholic extract by HPLC-DAD, Folin-Ciocalteu, Aluminum Chloride methods, DPPH assay, and, for the first time, we evaluated the antioxidant and anti-inflammatory activities on dermal fibroblasts. The phytochemical analysis confirmed the significant content of phenolic compounds (TPC 69.8 ± 0.6 mg GAE/g extract, TFC 15.07 mg CE/g extract) and the remarkable presence of rutin, quercetin, and isorhamnetin derivatives that give to the phytocomplex a good antioxidant activity as highlighted by the DPPH assay (IC50 of 8.04 ± 0.5 µg/mL). Through the reduction in NO• and ROS levels in human dermal fibroblasts, the biological tests demonstrated both the safety of the extract and its ability to counteract the inflammatory state generated by Interleukin-1β exposure. Our findings indicate that the antioxidant activities of the phytocomplex are strictly related to the anti-inflammatory action of the Sulla coronaria flowers extract, confirming that this plant could be a valuable source of bioactive molecules for cosmeceutical and nutraceutical applications. [ABSTRACT FROM AUTHOR]

The tripeptide glutathione plays important roles in many cell processes, including differentiation, proliferation, and apoptosis; in fact, disorders in glutathione homeostasis are involved both in the etiology and in the progression of several human diseases, including cancer. Natural compounds have been found to modulate glutathione levels and function beyond their role as mere antioxidants. For example, certain compounds can upregulate the expression of glutathione-related enzymes, increase the availability of cysteine, the limiting amino acid for glutathione synthesis, or directly interact with glutathione and modulate its function. These compounds may have therapeutic potential in a variety of disease states where glutathione dysregulation is a contributing factor. On the other hand, flavonoids' potential to deplete glutathione levels could be significant for cancer treatment. Overall, while natural compounds may have potential therapeutic and/or preventive properties and may be able to increase glutathione levels, more research is needed to fully understand their mechanisms of action and their potential benefits for the prevention and treatment of several diseases. In this review, particular emphasis will be placed on phytochemical compounds belonging to the class of polyphenols, terpenoids, and glucosinolates that have an impact on glutathione-related processes, both in physiological and pathological conditions. These classes of secondary metabolites represent the most food-derived bioactive compounds that have been intensively explored and studied in the last few decades. [ABSTRACT FROM AUTHOR]

Cynara cardunculus subsp. sylvestris (wild artichoke) is widespread in Sicily, where it has been used for food and medicinal purposes since ancient times; decoctions of the aerial parts of this plant have been traditionally employed as a remedy for different hepatic diseases. In this study, the phenolic profile and cell-free antioxidant properties of the leaf aqueous extract of wild artichokes grown in Sicily (Italy) were investigated. The crude extract was also tested in cells for its antioxidant characteristics and potential oxidative stress inhibitory effects. To resemble the features of the early stage of mild steatosis in humans, human HepG2 cells treated with free fatty acids at the concentration of 1.5 mM were used. HPLC-DAD analysis revealed the presence of several phenolic acids (caffeoylquinic acids) and flavonoids (luteolin and apigenin derivatives). At the same time, DPPH assay showed a promising antioxidant power (IC50 = 20.04 ± 2.52 µg/mL). Biological investigations showed the safety of the crude extract and its capacity to counteract the injury induced by FFA exposure by restoring cell viability and counteracting oxidative stress through inhibiting reactive oxygen species and lipid peroxidation and increasing thiol-group levels. In addition, the extract increased mRNA expression of some proteins implicated in the antioxidant defense (Nrf2, Gpx, and SOD1) and decreased mRNA levels of inflammatory cytokines (IL-6, TNF-α, and IL-1β), which were modified by FFA treatment. Results suggest that the total phytocomplex contained in wild artichoke leaves effectively modulates FFA-induced hepatic oxidative stress. [ABSTRACT FROM AUTHOR]

Brassica villosa subsp. drepanensis (Caruel) Raimondo & Mazzola, belonging to the Brassica oleracea complex, is a wild edible plant endemic to western Sicily and a relative of modern cultivated Brassica crops. In this study, the antioxidant properties, anti-inflammatory activities, enzymatic inhibition, and cytotoxicity in cancer cells of B. villosa subsp. drepanensis leaf ethanolic extract were analysed for the first time. In addition, its chemical profile was investigated partitioning the total 70% ethanol extract among ethyl acetate, n-butanol, and water to obtain three residues that were subjected to chromatographic separation. Two flavonol glycosides, a phenol glucoside, two amino acids, and purine/pyrimidine bases were obtained. The presence of the glucosinolate glucoiberin was detected in the water extract by UHPLC-MS analysis. The total polyphenol and flavonoid content of the 70% ethanol extract showed good antioxidant capacities and anti-inflammatory properties by reducing nitric oxide release and reactive oxygen species levels and increasing glutathione in lipopolysaccharide-stimulated RAW 264.7 cells. The extract inhibited the enzymatic activity of α-amylase, α-glucosidase, and, significantly, of lipase. The MTT assay showed that the extract did not affect the viability of normal HFF-1 and RAW 264.7 cells. Among the cancer cell lines tested, an antiproliferative action was only observed in CaCo-2. The cytotoxicity of the extract was further confirmed by LDH release assay and by the destabilization of the oxidative balance. Results confirmed the antioxidant properties of the crude extract responsible for the anti-inflammatory effect on healthy cells and cytotoxicity in cancer cells. [ABSTRACT FROM AUTHOR]

Castanea sativa is particularly exploited in the Mediterranean basin, for fruit and wood production. Several authors studied the possible effects of C. sativa compounds as interesting ingredients for food supplements, cosmetics and pharmaceutical products. Some of the most antioxidant molecules are not always found in fruits, but in matrices richer in polyphenols like flowers or shells. In the present study, antioxidant, antimicrobial and anticancer properties of C. sativa (Fagaceae) aqueous and ethanolic pellicle extracts were investigated for the first time. The ethanolic extract had the highest total polyphenol and flavonoid content and was also found to have the highest antioxidant activity in dose dependent manner. The antimicrobial tests showed that only ethanolic extract inhibited the growth of bacteria, whereas no activity was recorded by the aqueous extract. The cytotoxicity of both extracts was evaluated on MCF-7 breast cancer cell line by the MTT assay and reactive oxygen species (ROS) determination, suggesting a potential antiproliferative activity. Our results suggested that C. sativa ethanolic pellicle extract might represent a good natural source of antioxidant, antimicrobial and anticancer agents with potential health benefits. [ABSTRACT FROM AUTHOR]

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]

Acquaviva R, Lanteri R, Li Destri G, Caltabiano R, Vanella L, Lanzafame 8, Di Cataldo A, Li Volti G, Di Giacomo C. Beneficial effects of rutin and L-arginine coadministration in a rat model of liver ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol 296: G664-G670, 2009. First published December 24, 2008; doi: 10.1152/ajpgi.90609.2008.-Reperfusion following liver ischemia results in oxidative stress leading to liver injury. The aim of this study was to investigate the combined effects of two antioxidant agents, rutin and L-arginine, in rat liver ischemia-reperfusion (I/R). Male Wistar rats were divided into five groups: 1) sham operated, 2) hR. 3) hR + rutin, 4) hR + L-arginine, and 5) YR + rutin + L-arginlne. Plasmatic and hepatic levels of alanine transaminase (ALT), aspartate transaminase (AST), lipid peroxides (LOOH), and thiol groups (RSH) were examined, as well as DNA fragmentation and liver histopathology. Furthermore, to elucidate the pathophysiological processes involved in the antioxidant mechanism(s) of rutin and L-arginine, we assessed the expression of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) isoforms and heme oxygenase-1 (HO-1), both playing key roles in the biochemical cascade of liver injury. Significant increase in plasmatic ALT and AST activities were observed in untreated YR rats compared with sham-operated animals, whereas treatment with rutin or L-arginine in YR rats reduced hepatic damage. Interestingly, combined therapy with rutin and Larginine resulted in a further reduction of plasmatic ALT and AST activities compared with rutin or L-arginine alone. These results were further confirmed by the analysis of DNA fragmentation, LOOH, RSH groups, and liver histopathology, which showed the highest protective effects following the coadministration of rutin and Larginine. Finally, the combined therapy protocol resulted in a significant induction of liver HO-1 and a concomitant reduction of iNOS expression that may both be responsible for the beneficial effects of the proposed pharmacological protocol. [ABSTRACT FROM AUTHOR]

Pathophysiological mechanisms correlating diabetes mellitus with associated complications are still not completely clear, even though oxidative stress seems to play a pivotal role. Literature data suggest that cell damages induced by hyperglycemia, although multifactorial, have a common pathway in oxidative/nitrosative stress. The present study evaluated the effects of Betula etnensis Raf. bark extract, a plant belonging to the Betulaceae family endemic to Sicily, on oxidative stress and in preventing and/or retarding diabetes-associated complications in streptozotocin diabetic rats treated with the extract at dose of 0.5 g/kg body weight per day for 28 consecutive days. The extract administration significant decreased food and water intake, fasting blood glucose, weight loss and polyuria, compared with untreated diabetic animals. Furthermore, oxidative stress markers particularly, lipid hydroperoxides (LOOH) and nitrite/nitrate levels, non-proteic thiol groups (RSH), γ-glutamyl-cysteine-synthetase (γ-GCS) activities and expression, heme oxygenase-1 (HO-1), endothelial and inducible nitric oxide synthases (i-NOS e-NOS) expression, significantly changed by streptozocin treatment, were markedly restored both in plasma and tissues together with nuclear sirtuins activity (Sirt1). Results suggested that B. etnensis bark alcoholic extract is able to counteract oxidative stress and to ameliorate some general parameters related to diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Diabetes mellitus is associated with a higher oxidative stress and reduced activity of the antioxidant defense system in different brain regions. Results from numerous studies reported impaired cognitive and neurochemical function in diabetic patients and streptozotocin induced diabetic rodents. It is well established that polyphenols exert potent antioxidant and protective functions. Based on recent findings, one potential target for the antioxidant/antinflammatory properties of polyphenols is the heme oxygenase (HO)-1 pathway. Among various compounds tested silibinin, the main component of silymarin, has been shown to possess a strong antioxidant effect in various experimental models; however a study on the possible neuroprotective effect of this compound on the brain of diabetic animals is currently lacking. Therefore, we studied and measured in lean mice (db/m) and knock out mice for the leptin receptors mice (db/db) the effect of silibinin on HO-1 protein levels, non proteic thiol groups, isoprostanes and 8-OH deoxyguanosine (markers of lipid peroxidation and DNA damage, respectively) in different brain regions. Our results showed that HO-1 is differently expressed in various brain regions in db/db mice when compared to lean animals. Furthermore, silibinin provides DNA protection and reduces oxidative stress in a brain specific area, in part via the activation of the HO system. Silibinin may provide a valid tool to counteract oxidative stress in the diabetic status in the central nervous system under diabetic condition. [Copyright &y& Elsevier]