Thermogenic Modulation of Adipose Depots: A Perspective on Possible Therapeutic Intervention with Early Cardiorenal Complications of Metabolic Impairment.

Cardiovascular complications of diabetes and obesity remain a major cause for morbidity and mortality worldwide. Despite significant advances in the pharmacotherapy of metabolic disease, the available approaches do not prevent or slow the progression of complications. Moreover, a majority of patients present with significant vascular involvement at early stages of dysfunction prior to overt metabolic changes. The lack of disease-modifying therapies affects millions of patients globally, causing a massive economic burden due to these complications. Significantly, adipose tissue inflammation was implicated in the pathogenesis of metabolic syndrome, diabetes, and obesity. Specifically, perivascular adipose tissue (PVAT) and perirenal adipose tissue (PRAT) depots influence cardiovascular and renal structure and function. Accumulating evidence implicates localized PVAT/PRAT inflammation as the earliest response to metabolic impairment leading to cardiorenal dysfunction. Increased mitochondrial uncoupling protein 1 (UCP1) expression and function lead to PVAT/PRAT hypoxia and inflammation as well as vascular, cardiac, and renal dysfunction. As UCP1 function remains an undruggable target so far, modulation of the augmented UCP1-mediated PVAT/PRAT thermogenesis constitutes a lucrative target for drug development to mitigate early cardiorenal involvement. This can be achieved either by subtle targeted reduction in UCP-1 expression using innovative proteolysis activating chimeric molecules (PROTACs) or by supplementation with cyclocreatine phosphate, which augments the mitochondrial futile creatine cycling and thus decreases UCP1 activity, enhances the efficiency of oxygen use, and reduces hypoxia. Once developed, these molecules will be first-in-class therapeutic tools to directly interfere with and reverse the earliest pathology underlying cardiac, vascular, and renal dysfunction accompanying the early metabolic deterioration. SIGNIFICANCE STATEMENT: Adipose tissue dysfunction plays a major role in the pathogenesis of metabolic diseases and their complications. Although mitochondrial alterations are common in metabolic impairment, it was only recently shown that the early stages of metabolic challenge involve inflammatory changes in select adipose depots associated with increased uncoupling protein 1 thermogenesis and hypoxia. Manipulating this mode of thermogenesis can help mitigate the early inflammation and the consequent cardiorenal complications.

Production of functional pita bread using date seed powder.

Functional foods represent a novel approach to prevent diet-related diseases. Due to its excellent nutritional and antioxidant properties, date seed was used to develop functional pita bread. Flour was replaced by 5, 10, 15 and 20 % date seed powder. Regular and whole wheat pita breads were the references. Results clearly showed that date seed powder containing bread contained comparable dietary fibers levels as in whole wheat bread and higher levels of flavonoids and phenolics. Date seed powder containing breads were particularly rich in flavan-3-ols whereas reference breads did not contain any of them and only a limited amount of other phenolic compounds. They also exhibited a much higher antioxidant capacity. Additionally, compared to regular bread, acrylamide level was significantly lower in 5 % date seed powder containing bread, and lower in all date seed powder containing breads compared to whole wheat bread. Date seed powder supplemented bread appears as a promising functional ingredient to prevent chronic diseases.

Polyphenolic compounds in date fruit seed (Phoenix dactylifera): characterisation and quantification by using UPLC-DAD-ESI-MS.

BACKGROUND: Date fruit seeds have been demonstrated to possess high antioxidant activities due to their high content of flavonoids and phenolic compounds. The objective of this work was to identify and quantify the phenolic composition of date seeds. METHODS: Two UPLC-DAD-ESI-MS analyses were performed on the seed of the Khalas variety as follows: (1) an analysis of simple phenolic compounds [phenolic acids, hydroxycinnamic acids, flavonols, flavones, flavan-3-ols (monomers, dimers and trimers)]; and (2) an analysis of all flavan-3-ols (monomers, and proanthocyanidin oligomers and polymers) after depolymerisation. RESULTS: The amount of total phenolic compounds before depolymerisation was found to be 2.194 ± 0.040 g kg(-1) date seed. The analysis of flavan-3-ol monomers and constitutive units of proanthocyanidins after depolymerisation revealed 50.180 ± 1.360 g kg(-1) flavan-3-ols with 46.800 ± 1.012 g kg(-1) epicatechin and 3.380 ± 0.349 g kg(-1) catechin. CONCLUSION: The results indicate that date seeds are a very rich source of bioactive compounds, thus constituting strong candidates for functional food additives and nutraceuticals.

Soybean peroxidase-mediated degradation of an azo dye- a detailed mechanistic study.

BACKGROUND: Peroxidases are emerging as an important class of enzymes that can be used for the efficient degradation of organic pollutants. However, detailed studies identifying the various intermediates produced and the mechanisms involved in the enzyme-mediated pollutant degradation are not widely published. RESULTS: In the present study, the enzymatic degradation of an azo dye (Crystal Ponceau 6R, CP6R) was studied using commercially available soybean peroxidase (SBP) enzyme. Several operational parameters affecting the enzymatic degradation of dye were evaluated and optimized, such as initial dye concentration, H2O2 dosage, mediator amount and pH of the solution. Under optimized conditions, 40 ppm dye solution could be completely degraded in under one minute by SBP in the presence of H2O2 and a redox mediator. Dye degradation was also confirmed using HPLC and TOC analyses, which showed that most of the dye was being mineralized to CO2 in the process. CONCLUSIONS: Detailed analysis of metabolites, based on LC/MS results, showed that the enzyme-based degradation of the CP6R dye proceeded in two different reaction pathways- via symmetric azo bond cleavage as well as asymmetric azo bond breakage in the dye molecule. In addition, various critical transformative and oxidative steps such as deamination, desulfonation, keto-oxidation are explained on an electronic level. Furthermore, LC/MS/MS analyses confirmed that the end products in both pathways were small chain aliphatic carboxylic acids.

Use of 4-D proteomics to differentiate between bovine and camel lactoferrin.

Lactoferrin is a multifunctional protein that has various biological activities and applications. However, different sources of lactoferrin may have different properties and characteristics. In this study, we hypothesized that ultra-performance liquid chromatography quadrupole time-of-flight mass spectroscopy (UPLC-QTOF-IMS) coupled with UNIFI software can differentiate bovine lactoferrin from camel lactoferrin based on the unique peptides produced by trypsin digestion. We enzymatically digested the proteins using trypsin and analyzed the resulting peptides using Uniport software and in silico digestion. We identified 14 marker peptides that were unique to bovine lactoferrin and could be used to distinguish it from camel lactoferrin. We also demonstrated the advantages of 4D proteomics over 3D proteomics in separating and identifying peptides based on their mass, retention time, intensity, and ion mobility. This method can be applied to other lactoferrin sources and improve the quality control and authentication of lactoferrin products.

Physicochemical and Sensory Properties and Shelf Life of Block-Type Processed Cheeses Fortified with Date Seeds (Phoenix dactylifera L.) as a Functional Food.

Processed cheese has rapidly been established as a commercial product in recent years. A new ingredient, a byproduct from date fruit seed (DFS), was obtained and tested as a fortified fiber from food industrial waste in block-type processed cheese. This is the first inclusive investigation to report such a test. Different concentrations of DFS (0%, 5%, 10%, 15%, and 20%) were added to block-type processed cheese as a partial substitution for butter. The current investigation was undertaken to estimate the impact of the partial substitution of butter by DFS and its effect on the product's quality in terms of its shelf life and physicochemical, microstructure, color, and sensory properties. Quality was assessed over a 150-day storage period. The results indicate that adding DFS to cheese increased its nutritional value due to the addition of fiber. Additionally, the texture profile of cheese was decreased in terms of hardness, adhesion, springiness, and cohesiveness. The overall structure of cheeses became less compact and had a more open cheese network, which increased with increasing DFS% and duration of storage. Moreover, DFS exhibited the darkest color with increasing ratios of supplementary DFS and duration of storage. Based on the results found in the present investigation, it was concluded that an acceptable quality of block-type processed cheese could be achieved using DFS fiber at 5% and 10% levels of fortification.

Valorization of Second-Grade Date Fruit Byproducts and Nonstandard Sweet Potato Tubers to Produce Novel Biofortified Functional Jam.

Byproducts of second-grade dates and sweet potato tubers of noncommercial standard are produced along with the main product and are just as important as the main product but cannot be sold in the open market, as they may not be considered acceptable by consumers. Such byproducts can be valorized through the manufacture of a wide range of functional food products with high market appeal, such as jams. The research approach of this study included measuring antioxidant activity, total flavonoids, polyphenols, physicochemical and color indices, pH, and total sugar, as well as conducting a sensory evaluation, of mixed jams composed of different ratios of date jam (DFJ) to sweet potato jam (SPJ), namely, DP1 (80:20), DP2 (70:30), DP3 (60:40), and DP4 (50:50). To date, no other studies have considered producing mixed jam from dates and sweet potato byproducts. The sensory evaluation results indicated that jam DP4 (consisting of 50% date and 50% sweet potato) had the maximum overall acceptability. This investigation reveals the potential of using mixed byproducts in jams as natural functional ingredients, suggesting the economic value of valorization byproducts as low-cost ingredients to expand the properties, nutritional value, antioxidant content, and overall acceptability of jams. The discovered optimal mixed fruit jam has significant potential for further development as a commercial product.

Palm Fruit (Phoenix dactylifera L.) Pollen Extract Inhibits Cancer Cell and Enzyme Activities and DNA and Protein Damage.

Palm fruit pollen extract (PFPE) is a natural source of bioactive polyphenols. The primary aim of the study was to determine the antioxidant, antimicrobial, anticancer, enzyme inhibition, bovine serum albumin (BSA), and DNA-protective properties of PFPE and identify and quantify the phenolic compounds present in PFPE. The results demonstrated that PFPE exhibited potent antioxidant activity in various radical-scavenging assays, including (2,2-diphenyl-1-picrylhydrazyl) (DPPH•), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•), nitric oxide (NO), ferric-reducing/antioxidant power (FRAP), and total antioxidant capacity (TAC). PFPE also displayed antimicrobial activity against several pathogenic bacteria. Similarly, PFPE reduced acetylcholinesterase, tyrosinase, and α-amylase activities. PFPE has been proven to have an anticancer effect against colon carcinoma (Caco-2), hepatoma (HepG-2), and breast carcinoma (MDA) cancer cells. Apoptosis occurred in PFPE-treated cells in a dose-dependent manner, and cell cycle arrest was observed. Furthermore, in breast cancer cells, PFPE down-regulated Bcl-2 and p21 and up-regulated p53 and Caspase-9. These results show that PFPE constitutes a potential source of polyphenols for pharmaceutical, nutraceutical, and functional food applications.

Antioxidant, Anti-Inflammatory, Antimicrobial, and Anticancer Activities of Pomegranate Juice Concentrate.

Pomegranate juice concentrate (PJC) is a rich source of polyphenols, which exhibit significant antioxidant activity and potential health benefits for disease prevention and therapy. In this study, the polyphenolic profile of PJC was investigated for the first time, and it was found that PJC can inhibit oxidative damage to bovine serum albumin (BSA) and deoxyribonucleic acid (DNA), as well as acetylcholinesterase, α-amylase, and tyrosinase activities. The primary polyphenols identified in PJC were 4-Hydroxy-3-Methoxybenzoate, epicatechin, catechin, rutin, ferulic acid, P-coumaric acid, and cinnamic acid. Additionally, PJC demonstrated potent antibacterial effects against human pathogens such as Streptococcus mutans and Aeromonas hydrophila and dose-dependently reduced the proliferation of colorectal, breast, and hepatic cancer cells via apoptosis. Furthermore, PJC blocked B-cell lymphoma 2 (BCl-2) and the expression of a potent cyclin-dependent kinase inhibitor (P21) and enhanced tumor protein (P53) expression, compared to both untreated cells and cells treated with fluoropyrimidine 5-fluorouracil (5-FU). As a result, PJC may be a beneficial ingredient in the formulation of emerging natural-compound-based chemotherapy and functional foods and could be utilized by the food, nutraceutical, and pharmaceutical industries.

Grape seed proanthocyanidin extract inhibits DNA and protein damage and labile iron, enzyme, and cancer cell activities.

Grape seed extract from (Vitis vinifera) (VGSE) is an excellent source of various polyphenols that exhibit highly potent antioxidant and disease prevention properties. Although numerous biological activities, with potential for improving human health, have been reported for VGSE, there is a lack of data relating to the health benefits of VGSE on DNA damage, protein damage, labile iron activity, and enzyme inhibitory effects. This investigation demonstrated, for the first time, that VGSE inhibits DNA and BSA damage and labile iron activity in-vitro. Moreover, VGSE also inhibited in-vitro activities of AChE, tyrosinase, and α-amylase. VGSE treatment significantly reduced viability of MCF-7, Hep-G2, Caco-2, and Huh-7 cells after 48-h treatments. The results obtained provide additional support for the purported health benefits of VGSE and reinforce its potential in disease prevention and therapy, especially in relation to cancer.

Polyphenol-Rich Date Palm Fruit Seed (Phoenix Dactylifera L.) Extract Inhibits Labile Iron, Enzyme, and Cancer Cell Activities, and DNA and Protein Damage.

Date palm fruit seed (Phoenix dactylifera L.) extract (DSE), an under-utilized resource, is a rich source of polyphenols with high potency for disease prevention and antioxidative activities. For the first time, the present study demonstrated that DSE inhibits labile iron activity and DNA and BSA damage and inhibits acetylcholinesterase and tyrosinase activities. Moreover, DSE reduces the proliferation of hepatic, colorectal, and breast cancer cells dose-dependently through apoptotic mechanisms. Furthermore, DSE significantly suppressed the expression of both BCl-2 and P21 genes and increased the P53 expression level when compared with the untreated cells and the 5-FU treated cells. These findings suggest a strong potential for DSE in protecting against the iron-catalyzed ferroptosis that results in programmed cell death. The results also confirm the efficacy of DSE against cancer cells. Therefore, DSE constitutes a valuable candidate for developing functional foods and for natural compound-based chemotherapy for the pharmaceutical and nutraceutical industries.

Nutritional quality of 18 date fruit varieties.

The aim of the present study was to analyze and compare the chemical and physical properties of 18 varieties of the date fruits from date palm (Phoenix dactylifera), which are regarded as popular fruit commodities among the populace of the Middle Eastern peninsula. Dietary fiber, proximate analysis, micronutrients (micro-elements and macro-elements) and physical properties (weight, length, and density) of the selected 18 leading varieties of dates cultivated in the United Arab Emirates-namely Khalas, Barhe, Lulu, Shikat alkahlas, Sokkery, Bomaan, Sagay, Shishi, Maghool, Sultana, Fard, Maktoomi, Naptit saif, Jabri, Khodary, Dabbas, Raziz and Shabebe-were determined and compared. Significant differences (P < 0.05) in the measured parameters were observed among the different varieties. However, the results depict that date fruits, depending on the variety, contain significant but quite variable amounts of macro-elements and micro-elements. The macro-elements measured are calcium, phosphorous, sodium, potassium and magnesium, while the essential micro-elements and the possibly essential micro-elements are iron, zinc, copper, manganese, cobalt and molybdenum, and aluminum, arsenic, barium, cadmium, chromium, nickel, lead, strontium and vanadium, respectively.

Effect of date seeds on oxidative damage and antioxidant status in vivo.

BACKGROUND: Date seeds have been shown to contain high amounts of antioxidants. However, in vivo studies on date seeds are lacking. Therefore the purpose of this study was to determine the effect of date seeds on oxidative damage and antioxidant status in vivo. Male Wistar rats were fed a basal diet containing 0, 70 or 140 g kg(-1) date seeds for 30 days. All three diets were isonitrogenous and isocaloric. Indication of oxidative damage was assessed in the liver and serum, and antioxidant status was assessed in the liver. Serum biochemical parameters, including indicators of tissue cellular damage and complete blood count with differential, were also determined. RESULTS: The results showed that date seeds significantly (P<0.05) reduced liver and serum malondialdehyde (a lipid peroxidative damage product) and serum lactate dehydrogenase and creatine kinase. Liver antioxidants (vitamin E, vitamin C, glutathione, superoxide dismutase, glutathione peroxidase and catalase), complete blood count with differential and other serum biochemical parameters assessed were not significantly altered by date seeds. CONCLUSION: The results obtained suggest a protective effect of date seeds against in vivo oxidative damage, possibly through the action of their bioactive antioxidants.

Nutritional value of 10 traditional dishes of the United Arab Emirates.

In the present study, 10 traditional dishes commonly consumed in the United Arab Emirates (U.A.E.) were chemically analyzed for proximate composition and mineral content. In addition, exchange lists for meal planning were developed for those dishes. Significant variations in nutritional value were found among the dishes. Protein content was lowest in chicken harese (3.33%) and highest in maleh (23.57%). The fat content ranged from 1.19% in ragag bread to15.47% in legemat (a sweet dish) while carbohydrate levels ranged from traces in maleh to 76.83% in ragag bread. Significant variations were also observed in major elements and trace elements among the dishes. Data from this study will be useful in calculating nutrient contributions from common traditional dishes in the U.A.E. as well as in planning normal and therapeutic diets. Further studies on the nutritional contributions of other traditional dishes in the U.A.E. are needed.

Inhibitory effects of honey from arid land on some enzymes and protein damage.

Although arid land honey is outstanding for its conventional uses in food and medicine, there is an absence of data regarding its health benefits from the perspective of enzyme inhibitory effects that are affirmed by the current study. For the first time, this investigation demonstrates that different types of honey exert inhibitory effects on the activities of angiotensin, tyrosinase, xanthine oxidase, -α -amylase, acetylcholinesterase, and lipase, in addition to the inhibition of bovine serum albumin damage. The present study also provides a comparison with perceived healthy honey from non-arid areas. The results indicated huge contrasts among honey samples through all assessed parameters. Results also demonstrated that at least one type of honey from arid land contained a higher inhibition effect when compared with honey from other regions. Therefore, a possible application of arid land honey and its active compounds can be the utilization as a therapeutic agent against several diseases.

The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators.

Iron overload is increasingly implicated as a contributor to the pathogenesis of COVID-19. Indeed, several of the manifestations of COVID-19, such as inflammation, hypercoagulation, hyperferritinemia, and immune dysfunction are also reminiscent of iron overload. Although iron is essential for all living cells, free unbound iron, resulting from iron dysregulation and overload, is very reactive and potentially toxic due to its role in the generation of reactive oxygen species (ROS). ROS react with and damage cellular lipids, nucleic acids, and proteins, with consequent activation of either acute or chronic inflammatory processes implicated in multiple clinical conditions. Moreover, iron-catalyzed lipid damage exerts a direct causative effect on the newly discovered nonapoptotic cell death known as ferroptosis. Unlike apoptosis, ferroptosis is immunogenic and not only leads to amplified cell death but also promotes a series of reactions associated with inflammation. Iron chelators are generally safe and are proven to protect patients in clinical conditions characterized by iron overload. There is also an abundance of evidence that iron chelators possess antiviral activities. Furthermore, the naturally occurring iron chelator lactoferrin (Lf) exerts immunomodulatory as well as anti-inflammatory effects and can bind to several receptors used by coronaviruses thereby blocking their entry into host cells. Iron chelators may consequently be of high therapeutic value during the present COVID-19 pandemic.

Nutritional quality evaluation of eighteen date pit varieties.

The pits from date palm fruits (Phoenix dactylifera L.) are nutrient dense but the nutrient composition across varieties has not been extensively studied. In the present study, 18 leading varieties of date pits from date fruits cultivated in the United Arab Emirates (Khalas, Barhe, Lulu, Shikat alkahlas, Sokkery, Bomaan, Sagay, Shishi, Maghool, Sultana, Fard, Maktoomi, Naptit Saif, Jabri, Kodary, Dabbas, Raziz and Shabebe) were analyzed and compared for their chemical and physical properties. Dietary fiber, proximate analysis, micronutrients, and physical properties (weight, length, and density) were determined. Significant differences (P<0.05) in the measured parameters were observed among the different varieties. The results show that date pits, depending on the variety, contain significant but quite variable amounts of macronutrients and micronutrients, but all varieties are excellent sources of dietary fiber and may therefore serve as important constituents of functional foods.

Effect of Ramadan fasting on markers of oxidative stress and serum biochemical markers of cellular damage in healthy subjects.

BACKGROUND/AIMS: Ramadan is a holy month for Muslims during which they abstain from eating, drinking and smoking from dawn to sunset. This makes Ramadan a unique model for studying the effects of altered meal patterns in humans. The aim of this study was to determine the effect of Ramadan fasting on markers of oxidative stress and serum biochemical markers of cellular damage in healthy subjects. METHODS: Fourteen healthy volunteers (9 men and 5 women aged 25-58 years) who fasted during Ramadan participated in the study. Blood sampling was conducted 2 days before Ramadan and on days 14 and 28 of Ramadan. The following were measured: (1) in serum, malondialdehyde (MDA), aspartate aminotransferase, alanine aminotransferase, creatine kinase, alkaline phosphatase, lactate dehydrogenase, blood urea nitrogen, total proteins, uric acid, albumin, glucose, triglycerides and total cholesterol; (2) in plasma, protein-bound carbonyls, alpha-tocopherol, gamma-tocopherol, retinol, vitamin C and carotenoids, and (3) in erythrocytes, MDA, glutathione, glutathione peroxidase and catalase. RESULTS: Erythrocyte MDA, serum glucose and triglycerides and plasma total carotenoids were significantly lower (p<0.05) on day 28 of Ramadan compared to before Ramadan. The rest of the variables were not significantly altered by Ramadan fasting. CONCLUSION: The results obtained indicate that with the exception of a slight reduction in lipid peroxidative damage in erythrocytes, Ramadan fasting does not alter oxidative stress parameters or biochemical markers of cellular damage in healthy subjects.

Isoflavone-rich soy isolate reduces lipid peroxidation in mouse liver.

The purpose of this study was to determine if an isoflavone-rich soy isolate affords protection against peroxidative damage in vivo. Weanling C57BL6 male mice were fed a basal diet (AIN-93G) supplemented with either nothing or 1.08 gram isoflavone-rich soy isolate/kg diet for 60 days. The soy isolate contained 400 mg/g isoflavone aglycones (226 mg/g genistein and 174 mg/g daidzein). Immediately following sacrifice liver was processed for measuring the levels of lipid peroxidation products, malondialdehyde (MDA) and conjugated dienes, and the levels of alpha-tocopherol, glutathione (GSH), and ascorbic acid, as well as the activities of catalase, selenium-dependent glutathione peroxidase (Se-GPx), selenium-nondependent glutathione peroxidase (non-Se-GPx), and superoxide dismutase (SOD). Compared with the control group, mice fed the diet supplemented with soy isolate had significantly (p<0.05) lower hepatic levels of MDA and conjugated dienes. The activities of catalase and SOD were significantly increased (p<0.05) in the liver of soy isolate-supplemented mice. The levels of vitamin E, GSH, and ascorbic acid and the activities of Se-GPx and non-Se-GPx were not significantly altered by the soy isolate. The results obtained provide experimental evidence that isoflavone supplementation confers protection against peroxidative damage to membrane lipids in vivo, possibly through enhancing the activities of the antioxidant enzymes catalase and SOD.

Effect of dietary inclusion of sugar syrup on production performance, egg quality and blood biochemical parameters in laying hens.

The effects of dietary inclusion of sugar syrup on quality of egg, cholesterol level, production performance, serum total protein and blood biochemical parameters were evaluated in laying hens. A total of 300 commercial Lohmann LSL hens (30 weeks of age) were randomly distributed into 3 dietary treatments which consisted of a normal corn diet containing corn-soy and 2 diets containing 5% and 10% sugar syrup. Each treatment was replicated 5 times (n = 20). Egg production, feed intake, body weight and egg weight of laying hens fed different diets were recorded. The experiment lasted for 20 weeks. The Haugh unit scores of hens fed diets with sugar syrup were significantly increased (P < 0.05) compared with the control treatment. The sugar syrup had no significant effect on liver enzymes, total protein, blood glucose and creatinine in all treatments. The eggs laid by hens fed sugar syrup diets had lower cholesterol level (P < 0.05) compared with those laid by hens fed the control diet. Electrophoresis analysis showed that comparable electrophoretic patterns were noticed between serum proteins of treatment groups. From the results, it can be concluded that sugar syrup diets and corn diets have similar effects on feed intake, body weight, production of eggs and blood biochemical parameters in layer hens, which suggests sugar syrup can be used as an energy source for replacing part of corn in poultry layer diets.