Distribution of antioxidants and phenolic compounds in flour milling fractions from hard red winter wheat

Mature wheat kernels contain three main parts:endosperm,bran,and germ.Flour milling results in multiple streams that are chemically different;however,the distribution of antioxidants and phenolic compounds has not been well documented in terms of conventional milling by-product streams.In this study,multiple analytical methods were used to investigate antioxidant activity and phenolic compound compositions of hard red winter wheat(whole ground wheat),the parts of a wheat kernel(bran,flour,germ),and wheat by-product streams(mill feed,red dog,shorts)for the first time.For each mill stream,phenolic compounds(total,flavonoid,and anthocyanin contents)were determined and antioxidant activities were evaluated with 1,1-diphenyl-2-picrylhydrazyl(DPPH)radical-scavenging activity,ferric reducing/antioxidant power(FRAP),and total antioxidant capacity assays.Significant differences(P<0.05)were observed in phenolic concentrations among fractions of bran,flour,and germ milled from the same kernels and noted that germ accounts for the majority of antioxidant properties,whereas bran contains a substantial portion of phenolic compounds and anthocyanins.Mill feed was high in phenolic content(5.29 mg FAE/g),total antioxidant capacity(866 mg/g),and antioxidant activity(up to 75% DPPH inhibition and 20.26μmol FeSO_(4)/g).The comprehensive information on distribution of antioxidants and phenolic compounds provides insights for future human consumption of commonly produced co-products from flour milling,and for selecting and using different milling fractions to make foods with improved nutritional properties.

Molecular Mechanism and Molecular Design of Lubricating Oil Antioxidants

To overcome the limitations of traditional experimental“trial and error”methods in lubricant additive design,a new molecular design method based on molecular structure parameters is established here.The molecular mechanism of the antioxidant reaction of hindered phenol,diphenylamine,and alkyl sulfide are studied via molecular simulations.Calculation results show that the strong electron-donating ability and high hydrogen-donating activity of the antioxidant molecule and the low hydrogen-abstracting activity of free radicals formed after dehydrogenation are the internal molecular causes of the shielding of phenol and diphenylamine from scavenging peroxy free radicals,and the strong electron-donating ability is the internal molecular cause of the high activity of thioether in decomposing alkyl hydrogen peroxide.Based on this antioxidant molecular mechanism,a molecular design rule of antioxidant is proposed,namely“high EHOMO,large Q(S),low bond dissociation energy BDE(O—H)and BDE(N—H)”.Two new antioxidants,PAS-I and PAS-II,are designed and prepared by chemical bonding of hindered phenol,diphenylamine,and sulfur atoms.Experimental results show that these antioxidants both have excellent antioxidant effects in lubricating oil,and that PAS-II is the superior antioxidant,consistent with theoretical predictions.

Dual Role of Plant Phenolic Compounds as Antioxidants and Prooxidants

Natural phenolic compounds are secondary metabolites found in a wide range of plants including food crops. As many of them are known to be antioxidants and can prevent several chronic and degenerative diseases in humans, they are a part of a healthy diet. However, these antioxidants can act as prooxidants under high phenolic concentration, high pH, or in the presence of transition metal ions such as Cu2+ or Fe3+, producing reactive oxygen species (ROS) including hydroxyl radicals resulting in oxidative stress and cell toxicity. While this can lead to pathogenesis including the development of various types of cancers, elevated levels of ROS are beneficial to kill malignant cells and foodborne pathogens to improve food safety. Thus, the dual nature of phenolic compounds allows them to act as antioxidants and prooxidants. Similarly, depending on the level of prooxidant activity, ROS can induce either pathogenesis or serve as a potential agent to kill malignant cells and foodborne pathogens.

Drought-Mediated Modulation in Metabolomic Profiling of Nigella Sativa Leaf, Growth, Ecophysiology and Antioxidants

Abiotic stresses,including drought,have been found to affect the growth and medicinal quality of numerous herbs.The proposed study aims to study the effects of different drought regimes on the metabolic profile,growth,ecophysiology,cellular antioxidants,and antioxidant potential of Nigella sativa(Black cumin)leaf.Forty-day-old seedlings of N.sativa were exposed to three regimes of drought(control,moderate and high)for a week.UPLCMS/MS metabolic profile of the leaf reveals the presence of more than a hundred metabolites belonging to anthocyanins,chalcones,dihydro flavonoids,flavonoids,flavanols,flavones,flavonoid carbonoside,isoflavones,etc.Drought was found to alter the contents of identified metabolites.Drought stress-induced oxidative stress and increased production of hydrogen peroxide and superoxide anions.Physiological changes,activities of antioxidant enzymes,contents of antioxidants,and proline were significantly high under drought to protect against the low water regimes.Furthermore,stressed leaf extract had higher antioxidant potential.Thus,N.sativa leaf bears multiple metabolic pathways and can tolerate a higher degree of drought or osmotic stress.

Relationship of nocturnal concentrations of melatonin, gamma-aminobutyric acid and total antioxidants in peripheral blood with insomnia after stroke： study protocol for a prospective non-randomized controlled trial

Melatonin and gamma-aminobutyric acid（GABA） have been shown to regulate sleep. The nocturnal concentrations of melatonin, GABA and total antioxidants may relate to insomnia in stroke patients. In this prospective single-center non-randomized controlled clinical trial performed in the China Rehabilitation Research Center, we analyzed the relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke. Patients during rehabilitation of stroke were recruited and assigned to the insomnia group or non-insomnia group. Simultaneously, persons without stroke or insomnia served as normal controls. Each group contained 25 cases. The primary outcome was nocturnal concentrations of melatonin, GABA and total antioxidants in peripheral blood. The secondary outcomes were Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale, Fatigue Severity Scale, Morningness-Eveningness Questionnaire（Chinese version）, and National Institute of Health Stroke Scale. The relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke was analyzed and showed that they were lower in the insomnia group than in the non-insomnia group. The severity of stroke was higher in the insomnia group than in the non-insomnia group. Correlation analysis demonstrated that the nocturnal concentrations of melatonin and GABA were associated with insomnia after stroke. This trial was registered at Clinical Trials.gov, identifier： NCT03202121.

Relationships among alcoholic liver disease,antioxidants,and antioxidant enzymes

Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide.The metabolism of ethanol generates reactive oxygen species,which play a significant role in the deterio-ration of alcoholic liver disease(ALD).Antioxidant phytochemicals,such as polyphenols,regulate the expression of ALD-associated proteins and peptides,namely,catalase,superoxide dismutase,glutathione,glutathione peroxidase,and glutathione reductase.These plant antioxidants have electrophilic activity and may induce antioxidant enzymes via the Kelch-like ECH-associated protein 1--NF--E2--related factor--2 pathway and antioxidant responsive elements.Furthermore,these antioxidants are reported to alleviate cell injury caused by oxidants or inflammatory cytokines.These phenomena are likely induced via the regulation of mitogen--activating protein kinase(MAPK)pathways by plant antioxidants,similar to preconditioning in ischemia-reperfusion models.Although the relationship between plant antioxidants and ALD has not been adequately investigated,plant antioxidants may be preventive for ALD because of their electrophilic and regulatory activities in the MAPK pathway.

The research and development on the antioxidants in prevention of diabetic complications

Diabetes mellitus can damage the eyes,kidneys,nerves and heart.Microvascular and macrovascular disorders are the leading causes of morbidity and mortality in diabetic patients.Hyperglycemia can increase the indicators of lipid peroxidation and oxidative stress in which free radicals have the main role in the pathogenesis of these complications.Therefore,antioxidants which combat oxidative stress should be able to prevent and repair free radicals induced damages.Although free radicals contribute to kidney damage,atherosclerosis,diabetes,heart disease,nephrotoxicity and hepatotoxicity; however,clinical trials do not uniquely confirm a substantial impact on diabetic damage.It seems that antioxidants in vegetables,fruits and grains help preventing diabetes complications; however,there is little evidence that taking single antioxidants such as vitamin E or vitamin C protect these complications.The findings about combination antioxidants are also complicated and not entirely clear.In this review paper we tried to present the role of oxidative stress on microvascular complications of type2 diabetes mellitus.Other objective of this paper is to review the new findings about the role of various antioxidants on prevention and treatment of diabetes mellitus as well as its complications including retinopathy,nephropathy and neuropathy.

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases(MMPs). Degradation of extracellular matrix(ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metallopro-teinase(TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK(reversion including cysteinerich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2,-9 and-14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species(ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.

Evaluation of anti-apoptotic activity of different dietary antioxidants in renal cell carcinoma against hydrogen peroxide

Objective:To evaluate the anti-apoptotic and radical scavenging activities of dietary phenolics, namely ascorbic acid,a-tocopherol acetate,citric acid,salicylic acid,and estimate H_2O_2induced apoptosis in renal cell carcinoma cells.Methods:The intracellular antioxidant potency of antioxidants was investigated.H_2O-2-induced apoptosis in RCC-26 was assayed with the following parameters:cell viability(%apoptosis),nucleosomal damage and DNA fragmentation, bcl-2 levels and flow cytometery analysis(ROS production evaluation).Results:Ine anticancer properties of antioxidants such as ascorbic acid,a- tocopherol acetate,citric acid,salicylic acid with perdurable responses were investigated.It was observed that these antioxidants had protective effect(anti-apoptotic activity) against hydrogen peroxide(H_2O_2) in renal cell carcinoma(RCC-26) cell line.Conclusions:This study reveals and proves the anticancer properties.However,in cancer cell lines anti-apoptotic activity can indirectly reflect the cancer promoter activity through radicals scavenging,and significantly protect nucleus and bcl-2.

The role of antioxidants and pro-oxidants in colon cancer

This review focuses on the roles antioxidants and prooxidants in colorectal cancer(CRC).Considerable evidence suggests that environmental factors play key roles in the incidence of sporadic CRC.If pro-oxidant factors play an etiological role in CRC it is reasonable to expect causal interconnections between the wellcharacterized risk factors for CRC,oxidative stress and genotoxicity.Cigarette smoking,a high dietary consumption of n-6 polyunsaturated fatty acids and alcohol intake are all associated with increased CRC risk.These risk factors are all pro-oxidant stressors and their connections to oxidative stress,the intestinal microbiome,intestinal microfold cells,cyclooxygenase-2 and CRCare detailed in this review.While a strong case can be made for pro-oxidant stressors in causing CRC,the role of food antioxidants in preventing CRC is less certain.It is clear that not every micronutrient with antioxidant activity can prevent CRC.It is plausible,however,that the optimal food antioxidants for preventing CRC have not yet been critically evaluated.Increasing evidence suggests that RRR-gamma-tocopherol(the primary dietary form of vitamin E)or other"non-alpha-tocopherol"forms of vitamin E(e.g.,tocotrienols)might be effective.Aspirin is an antioxidant and its consumption is linked to a decreased risk of CRC.

Effect of Commiphora mukul gum resin on hepatic marker enzymes,lipid peroxidation and antioxidants status in pancreas and heart of streptozotocin induced diabetic rats

Objective:To study the antioxidant efficacy of Commiphora mukul(C.mukul) gum resin ethanolic extract in streptozotocin(STZ) induced diabetic rats.Methods:The male Wistar albino rats were randomly divided into four groups of eight animals each:Control group(C),CM-treated control group(C_+CMEE),Diabetic control group(D),CM- treated diabetic group(D_+CMEE).Diabetes was induced by intraperitoneal injection of STZ(55 mg/kg/ bwt).After being confirmed the diabetic rats were treated with C.mukul gum resin ethanolic extract(CMEE) for 60 days.The biochemical estimations like antioxidant,oxidative stress marker enzymes and hepatic marker enzymes of tissues were performed.Results:The diabetic rats showed increased level of enzymatic activities aspartate aminotransaminase(AST),alanine aminotransaminase(ALT) in liver and kidney and oxidative markers like lipid peroxidation(LPO) and protein oxidation(PO) in pancreas and heart. Antioxidant enzyme activities were significantly decreased in the pancreas and heart compared to control group.Administration of CMEE(200 mg/kg bw) to diabetic rats for 60 days significantly reversed the above parameters towards normalcy.Conclusions:In conclusion,our data indicate the preventive role of C.mukul against STZ-induced diabetic oxidative stress;hence this plant could be used as an adjuvant therapy for the prevention and/or management of diabetes and aggravated antioxidant status.

Neuroprotection and antioxidants

Ischemia as a serious neurodegenerative disorder causes together with reperfusion injury many changes in nervous tissue. Most of the neuronal damage is caused by complex of biochemical reactions and substantial processes, such as protein agregation, reactions of free radicals, insufficient blood supply, glutamate excitotoxicity, and oxidative stress. The result of these processes can be apoptotic or necrotic cell death and it can lead to an irreversible damage. Therefore, neuroprotection and prevention of the neurodegeneration are highly important topics to study. There are several approaches to prevent the ischemic damage. Use of many modern therapeutical methods and the incorporation of several substances into the diet of patients is possible to stimulate the endogenous protective mechanisms and improve the life quality.

The in vitro effects of superoxide, some commercially available antioxidants and red palm oil on sperm motility

In this study, two commercially available superoxide scavengers, tetrakis （1-methyl-4-pyridyl） porphyrin （Mn[III]TMPyP） and superoxide dismutase （SOD）, as well as red palm oil （RPO）, a natural vegetable oil, had been used to investigate their possible in vitro effects against the toxic effects of superoxide （O2＋） on human sperm motility. Semen samples were obtained from 12 normozoospermic healthy volunteer donors aged between 19 and 23 years. The O2＋donor 2,3-dimetoxyl-l,4-naphthoquinone （DMNQ） （2.5 μmol· L^-1-100 μmol· L^-1） was added to normozoospermic post-swim-up sperm in the presence or absence of Mn（III）TMPyP （50 μmol· L^-1）, SOD （50 IU） or RPO （0.1% or 0.5%）. Computer-assisted semen analysis was used to analyze various motility parameters. The parameters of interest were percentage of motile cells, progressive motility, rapid cells and static cells. Concentrations of higher than 25 μmol· L^-1 DMNQ were detrimental to sperm motility. Mn（III）TMPyP was able to attenuate the effect of O2＋ on the motility parameters. In vitro addition of SOD and RPO showed harmful effects on sperm motility.

Antioxidants: Friend or foe?

Reactive oxygen species are the intermediates that are formed during the normal metabolic process which are effectively neutralized by the antioxidant system of the body.Any imbalance in this neutralization process causes oxidative stress which has been implicated as one of the cause in diseases such as Alzheimer's disease, cardiovascular disorders, cancer etc. Research has enabled the use of antioxidants as therapeutic agents in the treatment of various diseases. Literature also puts forth the negative effects of using antioxidants in the treatment of diseases. This review is a compilation of both the beneficial and detrimental effects of use of antioxidants in the treatment of diseases such as cancer, cardiovascular diseases, diabetes and oral diseases.

Oxidative stress and antioxidants in diabetes mellitus

Numerous studies have implicated oxidative stress in the development of complications of diabetes.During hyperglycemia,production of oxidant agents such as reactive oxygen species and reactive nitrogen species increases.This process,along with a decrease in the activity of antioxidant enzymes,induces oxidative stress in the body.This redox imbalance causes damage to vital biomolecules such as proteins,lipids and DNA and results in the generation of harmful products for the body.Mechanisms associated with the creation of oxidative stress conditions and subsequently complications of diabetes are explained through several pathways such as flux through the polyol pathway,intracellular production of advanced glycation end products precursors,protein kinase-C activation,and increased activities of the hexosamine pathway.On the other hand,the study of polymorphism in the antioxidant enzymes genes indicates that some of the gene polymorphisms reduce the antioxidant power of the enzymes.This article aims to review various studies to demonstrate the effect of oxidative stress on the pathogenesis of diabetes and the positive role of antioxidants on diabetic complications.

Effect of Type I and Type II Antioxidants on Oxidative Stability, Microbial Growth, pH, and Color in Raw Poultry Meat

Meat color is an intrinsic property that plays a major role in consumer’s perception. Lipid oxidation by-products as well as free iron can adversely affect meat color. This study was to compare the effect of Type I (radical quenching) antioxidants eugenol and rosmarinic acid (RA) to that of Type II (metal chelating) antioxidants milk mineral (MM), phytate, and sodium tri-polyphosphate (STPP) in raw ground chicken patties packed with a single layer of polyvinylchloride (PVC) overwrap. Packaged patties were stored at 4℃ and analyzed on 0, 1, 4, 7, and 10 days for pH, surface color, extent of lipid oxidation, oxymyoglobin content, and microbial load. Color stability was measured using Hunter MiniScan calorimeter (L*, a*, b* values). An effect was observed in L* values (P < 0.05) of meat color between treatments due to the type of antioxidant. Lightness values for STPP and phytate were low and differed (P < 0.05) from eugenol and rosmarinic acid. Milk mineral effectively preserved fresh color and slowed lipid oxidation in chicken patties by day 10. Aerobic plate counts increased over the entire testing period while values for lightness, redness, yellowness and chroma decreased indicating an increase in pH favored microbial spoilage of the meat or vice versa. By day 10, eugenol and MM were more effective and significantly different (P < 0.05) than STPP in controlling lipid oxidation measured as thiobarbituric acid reactive substances (0.198 mg/kg, 0.198 mg/kg, and 0.268 mg/kg, respectively). A positive correlation (r = 0.24, P < 0.005) between lipid oxidation and color saturation was observed indicating that poultry color darkened with increasing lipid oxidation levels.

Antioxidants in experimental ischemia-reperfusion injury of the testis: Where are we heading towards?

Testicular torsion(TT) is a medical emergency that primary affects newborns and young adolescents.It causes testicular injury due to the torsion of the spermatic cord and its components, initially in the venous blood flow and finally in the arterial blood flow.Prompt diagnosis and early surgical management are necessary in managing this urgent situation.The process of the pathophysiological events in ischemia-reperfusion is multifactorial and deals with the perception of the oxidative stress responsible for the consequences of ischemia/reperfusion(I/R) stress following TT.Duration and severity of torsion also play a significant role in the oxidative stress.A detrimental result of the defense system of the testes takes place resulting finally in testicular atrophy and impaired function.Antioxidant factors have been experimentally studied in an effort to front this state.They have been classified as endogenous or exogenous antioxidants.Endogenous antioxidants comprise a structure of enzymic enzymatic and nonenzymic enzymatic particles presented within cytoplasm and numerous other subunits in the cells.Exogenous antioxidants include a variety of natural and pharmaceutical agents that may prevent or ameliorate the harmful effects of I/R injury.In this study we review those factors and their ability to enhance the oxidative status of the testis.A feature insight into where we are heading is attempted.

Can antioxidants predispose to cancer recurrence?

Objective:To measure and compare pre- and post-treatment levels of serum total glutathione -S-transferase(GST) in stageⅣcervical cancer patients and erythrocytic glutathione(GSH) and malondialdehyde(MDA) and plasma ceruloplasmin(CP) and total GST in stageⅣoral cancer patients and to correlate with the response to treatment during a two year follow-up period in respective cancer groups.Methods:Thirty-four biopsy-proven stageⅣoral cancer and cervical cancer patients(n=17 in each group) who underwent same mode of treatment were chosen for this study.Erythrocytic MDA and GSH,CP and serum total GST were measured in all patients before the onset of treatment,and the GST level was only measured in cervical cancer patients after radiotherapy.The levels were compared with their respective prognosis in 2 years.Results:Oral cancer patients with higher pretreatment levels of GSH,CP and GST came with cancer recurrence within 2 years after the onset of treatment.Cervical cancer patients with higher post radiotherapy levels of serum total GST had higher recurrence tate.Conclusions: This study indicates there may be a role for these antioxidant parameters namely GST,GSH,CP in assessment of long term survival and prognosis of cancer patients.

Effect of natural and synthetic antioxidants on oxidative stability of FAMEs obtained from hevea brasiliensis

Biodiesel(fatty acid alkyl esters),an alternate to fossil fuel,has the tendency of autoxidation and hence requires antioxidants for long term storage.The influence of synthetic and natural antioxidants on the oxidative stability was analysed for fresh FAMEs(fatty acid methyl esters)obtained from hevea brasiliensis at 140 C.Higher activity was observed for synthetic antioxidants following the order of GA】BHT】DTBP】Q】GT-M】PH-M】GT-C,whereas the oxidative stability of stored FAMEs samples measured at 110 C reveals a nearly inverse trend.Storage stability was tested for the FAMEs obtained from hevea brasiliensis stored at 30 C,after addition of synthetic and natural antioxidants—butylated hydroxytoluene(BHT),2,6-di-tert-butylphenol(DTBP),quercetin(Q),gallic acid(GA),methanol extracts from green tea(GTM),pomegranate hull(PH-M),and chloroform extract of green tea(GT-C).Antioxidant activities above 1500 ppm was in the order of DTBP】BHT】GA】GT-C】GT-M】Q】PH-M.Synthetic antioxidants have been found more efficient to improve the storage stability of FAMEs obtained from hevea brasiliensis.DTBP in particular has the highest protection factor.

Liver disease and COVID-19:The link with oxidative stress,antioxidants and nutrition

Varying degrees of liver injuries have been reported in patients infected with the severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2).In general,oxidative stress is actively involved in initiation and progression of liver damage.The liver metabolizes various compounds that produce free radicals.Maintaining the oxidative/antioxidative balance is important in coronavirus disease 2019(COVID-19)patients.Antioxidant vitamins,essential trace elements and food compounds,such as polyphenols,appear to be promising agents,with effects in oxidative burst.Deficiency of these nutrients suppresses immune function and increases susceptibility to COVID-19.Daily micronutrient intake is necessary to support anti-inflammatory and antioxidative effects but for immune function may be higher than current recommended dietary intake.Antioxidant supplements(β-carotene,vitamin A,vitamin C,vitamin E,and selenium)could have a potential role in patients with liver damage.Available evidence suggests that supplementing the diet with a combination of micronutrients may help to optimize immune function and reduce the risk of infection.Clinical trials based on the associations of diet and SARS-CoV-2 infection are lacking.Unfortunately,it is not possible to definitively determine the dose,route of administration and best timing to intervene with antioxidants in COVID-19 patients because clinical trials are still ongoing.Until then,hopefully,this review will enable clinicians to understand the impact of micronutrient dietary intake and liver status assessment in COVID-19 patients.