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.

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.

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.

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.

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.

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.

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.

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.

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.

DNA and BSA damage inhibitory activities, and anti-acetylcholinesterase, anti-porcine α-amylase and antioxidant properties of Dolichos lablab beans.

The underutilized Kenyan variety of Dolichos lablab bean seeds serve as a good source of natural antioxidants, which can probably be effective in reducing the risk of occurrence of several diseases. This study was undertaken for the first time to address the limited knowledge regarding the antioxidant activities of lablab beans. Moreover, their DNA damage inhibitory activity, bovine serum albumin (BSA) damage inhibitory activity, and the inhibition of acetylcholinesterase and porcine α-amylase were also investigated. The antioxidant capacity of Dolichos lablab bean seeds extracted with methanol, water or methanol/water combination was evaluated by the ferric-reducing antioxidant power (FRAP) assay, free radical-scavenging activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO) radical-scavenging assay, and 2,20-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Results reported in the present study indicate that water, methanol and water/methanol extracts of lablab bean flour exhibited good antioxidant activity by effectively scavenging various free radicals, such as DPPH, NO, and ABTS radicals. The extracts also exhibited protective effects against DNA and BSA damage and inhibitory effects on porcine α-amylase. Findings of this study suggest that extracts from the lablab bean flour would have potential application in food supplements, and pharmaceutical and cosmetic industries.

Functional, bioactive, biochemical, and physicochemical properties of the Dolichos lablab bean.

The underutilized Kenyan variety of Dolichos lablab bean seeds serves as a good source of nutrients. This study was undertaken for the first time to address the limited knowledge regarding the bioactive, biochemical, physicochemical, and functional properties of Dolichos lablab beans. Proximate analysis, mineral, total and free amino acid profiles, total protein, total dietary and profile of fiber, carotenoids and fat soluble vitamins, total phenolics, and total flavonoids were evaluated. The results clearly show that Dolichos lablab beans contain many health-promoting components, such as fiber, proteins, minerals, and numerous phytochemicals endowed with useful biological activities, that allow it to contribute in a relevant way to the daily intake of these nutrients.

Graded levels of sugar syrup in broiler rations and its effect on growth performance and blood biochemical parameters.

Dietary energy for chickens normally includes cereal grains and fat. This innovative study investigated the effect of replacing part of the corn and fat in broiler chicken rations with graded levels of sugar syrup on growth performance and biochemical parameters. Experimental treatments consisted of feeding a corn-soy basal diet alone, or with graded levels of sugar syrup in increments of 5%, 10% and 15%. All starter diets were isonitrogenous and isocaloric. Body weight gain and efficiency of feed utilization of chicks fed the control diet alone were not significantly (P < 0.05) different from chicks fed diets supplemented with either 5% or 15% sugar syrup. Supplementation of sugar syrup to broiler diets had no significant effect on blood glucose, creatinine, total protein, or liver enzymes. Adding 5% sugar syrup to broiler rations significantly decreased blood cholesterol and triglycerides in chickens fed the sugar syrup diet compared with birds fed the control diet. In conclusion, the results shows sugar syrup can be used in poultry ration to replace part of the corn as a source of energy. These results allowed the authors to recommend the safe usage of sugar syrup in broiler rations.

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.

Physicochemical and biochemical properties of honeys from arid regions.

This study was conducted to evaluate the quality of 11 honeys from arid regions for first time, and compare it with 5 different honeys from non-arid regions. Mean values obtained for physicochemical parameters were: pH 4.76 ± 0.55; 17.32 ± 1.8% moisture; 80.95 ± 1.60 °Brix sugar; 69.05 ± 4.41% total sugar; 413.81 ± 178.48 µS cm(-1) electrical conductivity; 17.58 ± 7.68 meq/kg free acidity; 11.05 ± 3.18 meq/kg lactonic acidity; 28.63 ± 9.6 meq/kg total acidity; 12.66 ± 20.39 mg/kg HMF; 0.58 ± 0.03 water activity; and 0.98 ± 0.62 colour intensity. Potassium was the major mineral (1760.54 ± 685.24 mg/kg). All the samples showed considerable significant variations with reference to their physicochemical and biochemical properties, moreover, the total free amino acids and total carotenoids were 61.13 ± 63.16 mg/100g and 4.07 ± 10.05 µg/100g respectively. Acrylamide was detected only in one sample at 2.39 ± 0.22 µg/kg.

Bioactive components, antioxidant and DNA damage inhibitory activities of honeys from arid regions.

Honey serves as a good source of natural antioxidants, which are effective in reducing the risk of occurrence of several diseases. This study was undertaken to address the limited knowledge regarding the polyphenolic content, antioxidant and DNA damage inhibitory activities of honeys produced in arid regions and compare them with well-recognized honeys from non-arid regions. Different types of honey were assessed for their contents of total phenolics, total flavonoids, and certain types of phenolic compounds. The antioxidant capacity of honey was evaluated by ferric-reducing/antioxidant power assay (FRAP), free radical-scavenging activity (DPPH), nitric oxide (NO) radical-scavenging assay, total antioxidant activity, and DNA damage. Results clearly showed significant differences among honeys with all the evaluated parameters. Results also showed that one or more types of honey from arid regions contained higher levels of phenolic compounds, free radical-scavenging activities, or DNA damage inhibitory activities compared with the evaluated honeys from non-arid regions.

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.

Mitochondrial superoxide mediates labile iron level: evidence from Mn-SOD-transgenic mice and heterozygous knockout mice and isolated rat liver mitochondria.

Superoxide is the main reactive oxygen species (ROS) generated by aerobic cells primarily in mitochondria. It is also capable of producing other ROS and reactive nitrogen species (RNS). Moreover, superoxide has the potential to release iron from its protein complexes. Unbound or loosely bound cellular iron, known as labile iron, can catalyze the formation of the highly reactive hydroxyl radical. ROS/RNS can cause mitochondrial dysfunction and damage. Manganese superoxide dismutase (Mn-SOD) is the chief ROS-scavenging enzyme and thereby the primary antioxidant involved in protecting mitochondria from oxidative damage. To investigate whether mitochondrial superoxide mediates labile iron in vivo, the levels of labile iron were determined in the tissues of mice overexpressing Mn-SOD and heterozygous Mn-SOD-knockout mice. Furthermore, the effect of increased mitochondrial superoxide generation on labile iron levels was determined in isolated rat liver mitochondria exposed to various electron transport inhibitors. The results clearly showed that increased expression of Mn-SOD significantly lowered the levels of labile iron in heart, liver, kidney, and skeletal muscle, whereas decreased expression of Mn-SOD significantly increased the levels of labile iron in the same organs. In addition, the data showed that peroxidative damage to membrane lipids closely correlated with the levels of labile iron in various tissues and that altering the status of Mn-SOD did not alter the status of other antioxidant systems. Results also showed that increased ROS production in isolated liver mitochondria significantly increased the levels of mitochondrial labile iron. These findings constitute the first evidence suggesting that mitochondrial superoxide is capable of releasing iron from its protein complexes in vivo and that it could also release iron from protein complexes contained within the organelle.