Antioxidative peptides: enzymatic production, in vitro and in vivo antioxidant activity and potential applications of milk-derived antioxidative peptides

The beneficial effects of food-derived antioxidants in health promotion and disease prevention are being increasingly recognized. Recently, there has been a particular focus on milk-derived peptides; as a source of antioxidants, these peptides are inactive within the sequence of the parent protein but can be released during enzyme hydrolysis. Once released, the peptides have been shown to possess radical scavenging, metal ion chelation properties and the ability to inhibit lipid peroxidation. A variety of methods have been used to evaluate in vitro antioxidant activity, however, there is no standardised methodology, which hinders comparison of data. This review provides an overview on the generation of antioxidative peptides from milk proteins, the proposed mechanisms of protein/peptide induced antioxidant activity, in vitro measurement of antioxidant activity, in vivo evaluation of plasma antioxidant capacity and the bioavailability of antioxidative peptides. The understanding gained from other food proteins is referred to where specific data on milk-derived peptides are limited. The potential applications and health benefits of antioxidant peptides are discussed with a particular focus on the aging population. The regulatory requirements for peptide-based antioxidant functional foods are also considered.     

The content of phenolic compounds in medicinal plants of a botanical garden (Kaliningrad oblast)

The total content of phenolic compounds and antioxidants has been determined in medicinal plants (66 species from 31 families). Promising plant species with high antioxidant activity and maximum content of phenols have been found. Based on these data, the plants can be used as a basis for making innovative functional food products with an increased antioxidant effect.     

Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise

The liver is remarkably important during exercise outcomes due to its contribution to detoxification, synthesis, and release of biomolecules, and energy supply to the exercising muscles. Recently, liver has been also shown to play an important role in redox status and inflammatory modulation during exercise. However, while several studies have described the adaptations of skeletal muscles to acute and chronic exercise, hepatic changes are still scarcely investigated. Indeed, acute intense exercise challenges the liver with increased reactive oxygen species (ROS) and inflammation onset, whereas regular training induces hepatic antioxidant and anti-inflammatory improvements. Acute and regular exercise protocols in combination with antioxidant and anti-inflammatory supplementation have been also tested to verify hepatic adaptations to exercise. Although positive results have been reported in some acute models, several studies have shown an increased exercise-related stress upon liver. A similar trend has been observed during training: while synergistic effects of training and antioxidant/anti-inflammatory supplementations have been occasionally found, others reported a blunting of relevant adaptations to exercise, following the patterns described in skeletal muscles. This review discusses current data regarding liver responses and adaptation to acute and regular exercise protocols alone or combined with antioxidant and anti-inflammatory supplementation. The understanding of the mechanisms behind these modulations is of interest for both exercise-related health and performance outcomes.     

Suppression of the later stages of radiation-induced carcinogenesis by antioxidant dietary formulations

We have previously reported data from a long-term carcinogenesis study indicating that dietary antioxidant supplements can suppress radiation-induced malignant lymphoma and harderian gland tumors induced by space radiations (specifically, 1 GeV/n iron ions or protons) in CBA/J mice. Two different antioxidant dietary supplements were used in these studies: a supplement containing a mixture of antioxidant agents [l-selenomethionine (SeM), N-acetyl cysteine (NAC), ascorbic acid, co-enzyme Q10, α-lipoic acid and vitamin E succinate], termed the AOX supplement, and another supplement known as Bowman-Birk Inhibitor Concentrate (BBIC). In the present report, the results from the earlier analysis of the harderian gland data from the published long-term animal study have been combined with new data derived from the same long-term animal study. In the earlier analysis, harderian glands were removed from animals exhibiting abnormalities (e.g. visibly swollen areas) around the eyes at the time of euthanasia or death in the long-term animal study. Abnormalities around the eyes were usually due to the development of tumors in the harderian glands of these mice. The new data presented here focused on the histopathological results obtained from analyses of the harderian glands of mice that did not have visible abnormalities around the eyes at the time of necropsy in the long-term animal study. In this paper, the original published data and the new data have been combined to provide a more complete evaluation of the harderian glands from animals in the long-term carcinogenesis study, with all available harderian glands from the animals processed and prepared for histopathological evaluation. The results indicate that, although dietary antioxidant supplements suppressed harderian gland tumors in a statistically significant fashion when all glands were analyzed, the antioxidant diets were less effective at suppressing the incidence of all harderian gland tumors than they were at suppressing the incidence of large harderian gland tumors (>2 mm) observed at animal necropsy. These results suggest that the dietary antioxidant formulations had major suppressive effects in the later stages of radiation-induced carcinogenesis in vivo. It is hypothesized that the dietary antioxidant formulations prevented the early-stage neoplastic growths from progressing to fully developed, malignant tumors. In addition, the antioxidant dietary formulations were very effective at preventing the development of proton- or iron-ion-induced malignant tumors, because, in contrast to irradiated controls, no malignant tumors were observed in the irradiated animals maintained on either of the dietary antioxidant diets.     

Distachyasin: A new antioxidant metabolite from the leaves of Carex distachya

A novel antioxidant prenylated stilbenoid, distachyasin, has been isolated from the leaves of Carex distachya. Its structure has been elucidated on the basis of the spectroscopic characteristics. Bidimensional NMR, and crystallographic data and computational calculations have furnished important data useful for the characterization and the stereochemistry of the molecule. The compound has a tetracyclic skeleton derived from carexane. The compound has been assayed, for the antioxidant activity, by measuring its capacity to scavenge the H(2)O(2), nitric oxide, superoxide radical and to inhibit formation of TBARS (thiobarbituric acid reactive species).     

Effect of iodide on total antioxidant status of human serum

Free radicals and subsequent lipid peroxidation have been implicated in the pathogenesis of several degenerative and chronic diseases which are also treated frequently in spas. There are some data arising from previous studies which support an antioxidant or scavenging effect of iodide, being the essential ingredient of a therapeutically used local brine. The aim of the study was to test the antioxidant capacity of iodide in human serum. For this reason we measured the so-called Total Antioxidant Status determined by a colorimetric method, which reflects the protection against the attack of reactive oxygen species, including enzymic and non-enzymic antioxidants. Exogenous iodide applied as NaI, shows a significantly increased antioxidant capacity in comparison with NaCl at a concentration of 15 microM, which is quite comparable to the upper range of serum iodide levels achieved through balneo-therapeutical intervention. This result is in accordance with previous results from in vitro depolymerization experiments with hyaluronic acid. The antioxidant effect of 15 microM NaI has been found to be approaching the physiologically relevant concentration of ascorbic acid (50 microM).     

Modified peroxiredoxins as prototypes of drugs with powerful antioxidant action

The possibility of using modified peroxiredoxins as powerful antioxidant agents has been considered. Peroxiredoxins immobilized on perfluorocarbon emulsions and PTD-modified peroxiredoxins have been studied. It has been shown that peroxiredoxins efficiently bind to particles of perfluorocarbon emulsions, while maintaining their antioxidant properties. A panel of PTD-modified peroxiredoxins has been created and peroxiredoxins most effective both in antioxidant properties and the ability to penetrate cells have been selected. The modified peroxiredoxins obtained may serve as the basis for the design of drug with powerful antioxidant action.     

Lipid peroxidation and antioxidant defence enzyme activity in multiple sclerosis

Changes of state of lipid peroxidation and activity of antioxidant defence enzymes katalase, superoxide dismutase, glutathione peroxidase and glutathione reductase - in the brain and liver tissue of guinea-pig in conditions of different stages of experimental autoimmune encephalomyelitis (EAE; 11th, 21st, 27th day after inoculation) and in blood of multiple sclerosis (MS) patients with different types, degrees of severity and length of disease and blood level of reduced glutathione have been investigated. We have found, that the development of oxidative stress in animal organism during the disease development is progressive and intensive lipid peroxide oxidation without compensation by antioxidant mechanisms have been shown in the late period (27th day) of the experiment. In MS conditions this state was accompanied with high activity of demyelination process, severe degree of neuronal injury and length of disease above 5 years. In addition reduced glutathione level was increased in many patient groups: remitting type, light (II) degree of severity and among the patients with strongly disturbed neurological functions and long course of the disease. The obtained data allow us to suppose that the development of oxidative stress under demyelination conditions is a result of strong metabolic disorders and decrease of antioxidant defence in the patients during the disease development. The necessity of individual approaches for antioxidant therapy of patients with MS is discussed.     

DFT-Based Quantum Chemical Studies on Conformational, Electronic and Antioxidant Properties of Isobavachalcone and 4-Hydroxyderricin

Isobavachalcone and 4-hydroxyderricin which exhibit numerous biological activities are two major chalcone constituents isolated from the roots of Angelica keiskei KOIDZUMI. The conformational and antioxidant activity properties have been investigated by quantum chemical calculations based on the density functional theory, with the aim of verifying dominant antioxidant mechanisms. Three parameters of the O-H bond dissociation enthalpy (BDE), ionization potential (IP) and acidity in the presence of an implicit solvent for methanol are computed to estimate the antioxidant capacities. Results reveal that the order of antioxidant efficacies predicted by BDE and IP, different from that predicted by acidity, is in agreement with that obtained by experimental data. This demonstrates the importance of the hydrogen atom transfer and single electron transfer mechanisms to explain their capacities to scavenge 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical.     

Antioxidant activity of extracts from leaves and roots of Salvia miltiorrhiza Bunge, S. przewalskii Maxim., and S. verticillata L

Three Salvia species have been studied for antioxidant activity in methanol extracts from roots and leaves. The presence of the polyphenols and tanshinones was screened by HPLC and spectrophotometric assays and related to the antioxidant potential. The antioxidant capacity of the studied species is high, but differences between species and organs have been also revealed. Salvia przewalskii leaf extract was the strongest one in all tests, followed by Salvia miltiorrhiza root and Salvia verticillata leaf. Among the roots, the most active was S. miltiorrhiza extract, followed by S. verticillata. The antioxidant activity correlates to the total polyphenol and, depending on the assay, to the hydroxycinnamic acids content. The high content of tanshinones in both S. miltiorrhiza and S. przewalskii roots is unlikely to contribute to the antioxidant activity.     

Peptides with antioxidant properties identified from casein,whey, and egg albumin hydrolysates generated by two novel fungal proteases

Abstract

There are many diseases linked to oxidative stress, including cancer. Importantly, endogenous antioxidants are insufficient to protect against this process. Peptides derived from food proteins produced by hydrolysis have been investigated as exogenous antioxidants. The present study aimed to identify novel peptides with antioxidant potential produced from egg and milk proteins hydrolysis with two new fungal proteases isolated from Eupenicillium javanicum and Myceliophthora thermophila. The degree of hydrolysis at several time points was calculated and correlated to DPPH scavenging and metal chelating assays, all hydrolysates presented antioxidant activity. Casein hydrolyzed by the M. thermophila protease showed the best antioxidant activity. The identified sequences showed that the proportions of amino acids that influence antioxidant activity support the antioxidant assay. Our data reveal the conditions necessary for the successful generation of antioxidant peptides using two novel fungal proteases. This opens a potential new avenue for the design and manufacture of antioxidant molecules.     

Natural dibenzoxazepinones from leaves of Carex distachya: Structural elucidation and radical scavenging activity

Two new dibenzoxazepinones have been isolated from the leaves of Carex distachya, an herbaceous plant growing in the Mediterranean area. The structures have been elucidated on the basis of their spectroscopic properties. Bidimensional NMR (DQ-COSY, TOCSY, NOESY, ROESY, HSQC, and HMBC) furnished important data useful for the characterization of the molecules. The compounds have been assayed, for the antioxidant activity, by measuring its capacity to scavenge the DPPH, the superoxide anion, and nitric oxide radicals.     

Modified peroxiredoxins as prototypes of drugs a powerful antioxidant

The possibility of using modified peroxyredoxins as powerful antioxidant agents has been considered. Peroxyredoxins immobilized on perfluorocarbon emulsions and PTD-modified peroxyredoxins have been studied. It has been shown that peroxyredoxins efficiently bind to particles of perfluorocarbon emulsions, while maintaining their antioxidant properties. A panel of PTD-modified peroxyredoxins has been created and peroxyredoxins most effective both in antioxidant properties and the ability to penetrate cells have been selected. The modified peroxyredoxins obtained may serve as the basis for the design of drug with powerful antioxidant action.     

Protein Antioxidant Response to the Stress and the Relationship between Molecular Structure and Antioxidant Function

Background

Proteins have long been considered a principal target for oxidants as a result of their abundance in biological systems. However, there is increasing evidence about the significant antioxidant activity in proteins such as albumin. It is leading to new concepts that even consider albumin not only as an antioxidant but as the major antioxidant in plasma known to be exposed to continuous oxidative stress. Evidence presented here establishes a previously unrecognized relationship between proteins'' antioxidant capacity and structural stress.

Methodology/Principal Findings

A chemiluminiscence based antioxidant assay was achieved to quantify the antioxidant capacity of albumin and other proteins. The capabilities of proteins as antioxidants were presented, but in addition a new and powerful component of the protein antioxidant capacity was discovered. The intrinsic component, designated as Response Surplus (RS), represents a silent reserve of antioxidant power that awakens when proteins face a structural perturbation (stressor) such as temperature, short wave UV light, the same reactive oxygen species, and more extreme changes like glucose or aldehyde-mediated structural modifications. The work also highlights the importance of structural changes in protein antioxidant properties and the participation of sulfhydryl groups (SHs) in the RS antioxidant component. Based on recent evidence about the SH group chemistry, a possible model for explaining RS is proposed.

Conclusions/Significance

The data presented show the significant antioxidant behavior of proteins and demonstrate the existence of a previously unrecognized antioxidant response to the stress. Several implications, including changes in elementary concepts about antioxidants and protein function, should emerge from here.     

Effect of dietary sesame oil as antioxidant on brain hippocampus of rat in focal cerebral ischemia

Oxidative stress may be regarded as an imbalance between free radical production and opposing antioxidant defenses. Free radical oxidative stress is implicated in rat cerebral ischemia and naturaceutical antioxidants are dietary supplements that have been reported to have neuroprotective activity. Many studies have reported dietary sesame oil (SO) as an effective antioxidant. In the present study the neuroprotective effect of dietary SO was evaluated against middle cerebral artery occlusion (MCAO)-induced cerebral ischemia injury in rats. Rats were fed on diet (20% SO) for 15 days. The middle cerebral artery of adult male Wistar rat was occluded for 2 h and reperfused for 22 h. The antioxidant properties of brain were measured as levels of reduced glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxide (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS). A decrease in the activity of all the enzymatic and non-enzymatic antioxidants was observed along with an increase in lipid peroxidation (LPO) in MCAO group. The neurobehavioral activity of rats was also observed by using videopath analyzer. Dietary SO improved the antioxidant status in MCAO+SO group when compared with MCAO group. The results of neurobehavioral activity also support our biochemical data. The results obtained suggest protective effect of SO against cerebral ischemia in rat brain through their antioxidant properties.     

Dynamics of Vitamin E Action against LDL Oxidation

Vitamin E acts as an important antioxidant against oxidative modification of low density lipoprotein (LDL) which is accepted as an initial event in the pathogenesis of atherosclerosis. In spite of the numerous studies and reports, the action and role of vitamin E have not been fully elucidated yet. In this brief overview, the dynamics of action of vitamin E as an antioxidant have been discussed and it is emphasized that the total antioxidant potency is determined by the relative importance of many competing reactions which is determined by the reactivities and concentrations of substrates, radicals and antioxidant and by physical factors of the environment.     

Antioxidant properties of drugs used in Type 2 diabetes management: could they contribute to,confound or conceal effects of antioxidant therapy?

Objectives: This is a narrative review, investigating the antioxidant properties of drugs used in the management of diabetes, and discusses whether these antioxidant effects contribute to, confound, or conceal the effects of antioxidant therapy.Methods: A systematic search for articles reporting trials, or observational studies on the antioxidant effect of drugs used in the treatment of diabetes in humans or animals was performed using Web of Science, PubMed, and Ovid. Data were extracted, including data on a number of subjects, type of treatment (and duration) received, and primary and secondary outcomes. The primary outcomes were reporting on changes in biomarkers of antioxidants concentrations and secondary outcomes were reporting on changes in biomarkers of oxidative stress. Results: Diabetes Mellitus is a disease characterized by increased oxidative stress. It is often accompanied by a spectrum of other metabolic disturbances, including elevated plasma lipids, elevated uric acid, hypertension, endothelial dysfunction, and central obesity. This review shows evidence that some of the drugs in diabetes management have both in vivo and in vitro antioxidant properties through mechanisms such as scavenging free radicals and upregulating antioxidant gene expression. Conclusion: Pharmaceutical agents used in the treatment of type 2 diabetes has been shown to exert an antioxidant effect..