Farag, M. A., A. R. Khattab, H. H. Farghal, W. M. Ismail, and H. A. Fahmy, "Gas chromatography/mass spectrometry-based metabolite profiling of chia and quinoa seeds in comparison with wheat and oat.", Phytochemical analysis : PCA, 2024. Abstract

INTRODUCTION: With an increasing interest in healthy and affordable cereal intake, efforts are made toward exploiting underutilized cereals with high nutritional values.

OBJECTIVES: The current study aims to explore the metabolome diversity in 14 cultivars of chia and quinoa collected from Germany, Austria, and Egypt, compared with wheat and oat as major cereals.

MATERIAL AND METHODS: The samples were analyzed using gas chromatography-mass spectrometry (GC-MS). Multivariate data analysis (MVA) was employed for sample classification and markers characterization.

RESULTS: A total of 114 metabolites were quantified (sugars, alcohols, organic and amino acids/nitrogenous compounds, fatty acids/esters), but the inorganic and phenolic acids were only identified. Fatty acids were the major class followed by amino acids in quinoa and chia. Chia and oats were richer in sucrose. Quinoa encompassed higher amino acids. Quinoa and chia were rich in essential amino acids. Higher levels of unsaturated fatty acids especially omega 6 and omega 9 were detected in quinoa versus omega 3 in chia compared with oat and wheat, whereas ω6/ω3 fatty acid ratio of chia was the lowest. To the best of our knowledge, this is the first comprehensive metabolite profiling of these pseudo cereals.

CONCLUSION: Quinoa and chia, especially red chia, are more nutritionally valuable compared with oat and wheat because of their compositional profile of free amino acids, organic acids, and essential fatty acids, besides their low ω6/ω3 fatty acid ratio. Such results pose them as inexpensive alternative to animal proteins and encourage their inclusion in infant formulas.

m Fayek, N., M. H. Baky, Z. Li, I. Khalifa, E. Capanoglu, and M. A. Farag, "Metabolome classification of olive by-products from different oil presses providing insights into its potential health benefits and valorization as analyzed via multiplex MS-based techniques coupled to chemometrics.", Phytochemical analysis : PCA, 2024. Abstract

INTRODUCTION: The Olive (Olea europaea L.) is one of the most popular edible oil-producing fruits, consumed worldwide for its myriad nutritional and health benefits. Olive oil production generates huge quantities of by-products from the fruit, which are considered environmental hazards. Recently, more and more efforts have been made to valorize olive by-products as a source of low-cost, value-added food applications.

OBJECTIVE: The main objective of this study was to globally assess the metabolome of olive fruit by-products, including olive mill wastewater, olive pomace, and olive seeds from fruits from two areas, Siwa and Anshas, Egypt.

METHODS: Gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography with mass spectrometry (UPLC-MS) were used for profiling primary and secondary metabolites in olive by-products. Also, multivariate data analyses were used to assess variations between olive by-product samples.

RESULTS: A total of 103 primary metabolites and 105 secondary metabolites were identified by GC-MS and UPLC-MS, respectively. Fatty acids amounted to a major class in the olive by-products at 53-91%, with oleic acid dominating, especially in the pomace of Siwa. Mill wastewater was discriminated from other by-products by the presence of phenolics mainly tyrosol, hydroxyl tyrosol, and α-tocopherol as analyzed by UPLC-MS indicating their potential antioxidant activity. Pomace and seeds were rich in fatty acids/esters and hydroxy fatty acids and not readily distinguishable from each other.

CONCLUSION: The current work discusses the metabolome profile of olive waste products for valorization purposes. Pomace and seeds were enriched in fatty acids/esters, though not readily distinguishable from each other.

Peng, S., J. Wang, M. A. Farag, M. Salah, L. Liu, Y. Fang, and W. Zhang, "Impact of refining on phytochemicals and anti-inflammatory activity of papaya (Carica papaya L.) seed oil in LPS-stimulated THP-1 cells.", Food chemistry, vol. 459, pp. 140299, 2024. Abstract

This study investigated the changes in phytochemical composition and inflammatory response of crude papaya (Carica papaya L.) seed oil (CPO) and its refined forms (degummed, PDG; deacidified, PDA; decolorized, PDC; deodorized, PDO). Oils were analyzed for their phytochemical composition, oil quality parameters, antioxidant activity, and their inflammatory response in LPS-stimulated THP-1 macrophages. At higher refining degrees, particularly after deacidification, the contents of phytochemicals (sterols, tocopherols, and polyphenols) decreased while oxidation products increased. Both CPO (0.1-1.0 mg/mL) and PDG reduced the secretion and mRNA expression of LPS-stimulated inflammatory cytokines and mediators and also blocked the activation of the NF-κB pathway. PDA, PDC, and PDO showed low anti-inflammatory or even pro-inflammatory activity. Correlation analysis showed that 4 polyphenols and 2 phytosterols were responsible for the oil's anti-inflammatory effects. These findings indicated that moderate refining is suggested for papaya seed oil processing for retaining bioactive ingredients and anti-inflammatory ability.

Yang, L., Y. Gao, J. Gong, Q. Su, Z. Guo, M. A. Farag, and J. Xiao, "Myricetin ameliorates prediabetes through gut microbiota-SCFAs-Gpr43 axis.", Critical reviews in food science and nutrition, pp. 1-18, 2024.
Li, B., Y. Zhou, L. Wen, B. Yang, M. A. Farag, and Y. Jiang, "The occurrence, role, and management strategies for phytic acid in foods.", Comprehensive reviews in food science and food safety, vol. 23, issue 5, pp. e13416, 2024. Abstract

Phytic acid, a naturally occurring compound predominantly found in cereals and legumes, is the focus of this review. This review investigates its distribution across various food sources, elucidating its dual roles in foods. It also provides new insights into the change in phytic acid level during food storage and the evolving trends in phytic acid management. Although phytic acid can function as a potent color stabilizer, flavor enhancer, and preservative, its antinutritional effects in foods restrict its applications. In terms of management strategies, numerous treatments for degrading phytic acid have been reported, each with varying degradation efficacies and distinct mechanisms of action. These treatments encompass traditional methods, biological approaches, and emerging technologies. Traditional processing techniques such as soaking, milling, dehulling, heating, and germination appear to effectively reduce phytic acid levels in processed foods. Additionally, fermentation and phytase hydrolysis demonstrated significant potential for managing phytic acid in food processing. In the future, genetic modification, due to its high efficiency and minimal environmental impact, should be prioritized to downregulate the biosynthesis of phytic acid. The review also delves into the biosynthesis and metabolism of phytic acid and elaborates on the mitigation mechanism of phytic acid using biotechnology. The challenges in the application of phytic acid in the food industry were also discussed. This study contributes to a better understanding of the roles phytic acid plays in food and the sustainability and safety of the food industry.

Farag, M. A., E. M. Kabbash, A. Mediani, S. Döll, T. Esatbeyoglu, and S. M. Afifi, "Comparative Metabolite Fingerprinting of Four Different Cinnamon Species Analyzed via UPLC-MS and GC-MS and Chemometric Tools.", Molecules (Basel, Switzerland), vol. 27, issue 9, 2022. Abstract

The present study aimed to assess metabolites heterogeneity among four major species, including true cinnamon () and less explored species (, , and ). UPLC-MS led to the annotation of 74 secondary metabolites belonging to different classes, including phenolic acids, tannins, flavonoids, and lignans. A new proanthocyanidin was identified for the first time in along with several glycosylated flavonoid and dicarboxylic fatty acids reported for the first time in cinnamon. Multivariate data analyses revealed, for cinnamates, an abundance in versus procyandins, dihydro-coumaroylglycosides, and coumarin in . A total of 51 primary metabolites were detected using GC-MS analysis encompassing different classes, . sugars, fatty acids, and sugar alcohols, with true cinnamon from Malaysia suggested as a good sugar source for diabetic patients. Glycerol in , erythritol in , and glucose and fructose in from Malaysia were major metabolites contributing to the discrimination among species.

Tawfick, M. M., H. Xie, C. Zhao, P. Shao, and M. A. Farag, "Inulin fructans in diet: Role in gut homeostasis, immunity, health outcomes and potential therapeutics.", International journal of biological macromolecules, vol. 208, pp. 948-961, 2022. Abstract

Inulin consumption in both humans and animal models is recognized for its prebiotic action with the most consistent change that lies in enhancing the growth and functionality of Bifidobacterium bacteria, as well as its effect on host gene expression and metabolism. Further, inulin-type fructans are utilized in the colon by bacterial fermentation to yield short-chain fatty acids (SCFAs), which play important role in its biological effects both locally inside the gut and in systemic actions. The gut symbiosis sustained by inulin supplementation among other dietary fibers exerts preventive and/or therapeutic options for many metabolic disorders including obesity, type 2 diabetes mellitus, cardiometabolic diseases, kidney diseases and hyperuricemia. Although, gastrointestinal negative effects due to inulin consumption were reported, such as gastrointestinal symptoms in humans and exacerbated inflammatory bowel disease (IBD) in mice. This comprehensive review aims to present the whole story of how inulin functions as a prebiotic at cellular levels and the interplay between physiological, functional and immunological responses inside the animal or human gut as influenced by inulin in diets, in context to its structural composition. Such review is of importance to identify management and feed strategies to optimize gut health, for instance, consumption of the tolerated doses to healthy adults of 10 g/day of native inulin or 5 g/day of naturally inulin-rich chicory extract. In addition, inulin-drug interactions should be further clarified particularly if used as a supplement for the treatment of degenerative diseases (e.g., diabetes) over a long period. The combined effect of probiotics and inulin appears more effective, and more research on this synergy is still needed.

Qiu, Y., X. Gao, R. Chen, S. Lu, X. Wan, M. A. Farag, and C. Zhao, "Metabolomics and biochemical insights on the regulation of aging-related diabetes by a low-molecular-weight polysaccharide from green microalga .", Food chemistry: X, vol. 14, pp. 100316, 2022. Abstract

Globally, aging and diabetes are considered prevalent threats to human health. polysaccharide (CPP) is a natural active ingredient with multiple health benefits including antioxidant and hypolipidemic activities. In this study, the aging-related diabetic (AD) mice model was established to investigate the underlying hypoglycemic and antioxidant mechanisms of CPP. It improved superoxide dismutase, catalase (CAT), glutathione peroxidase (GSH-px), and malondialdehyde activities in liver and insulin secretion. CAT and GSH-px activity in the brain increased after CPP administration. In addition, through histopathological examinations, it was evident that injuries in the liver, brain, jejunum, and pancreas were restored by CPP. This restoration was likely mediated via the activation of glucagon-like peptide-1 receptor/FOXO-1 (forkhead box O1) pathway concurrent with the inhibition of interleukin-6 receptor/FOXO-1 pathway. Furthermore, metabolomics and correlation analysis revealed that CPP possibly relived AD through changes in insulin levels and declined oxidative stress as regulated by phenylpyruvic acid. These findings suggested that CPP exerted antioxidant and hypoglycemic roles in an AD mice model, thereby providing a sound scientific foundation for further development and utilization of CPP.

Chen, Y., Y. Ouyang, X. Chen, R. Chen, Q. Ruan, M. A. Farag, X. Chen, and C. Zhao, "Hypoglycaemic and anti-ageing activities of green alga Ulva lactuca polysaccharide via gut microbiota in ageing-associated diabetic mice.", International journal of biological macromolecules, vol. 212, pp. 97-110, 2022. Abstract

Ageing-related type 2 diabetes is a significant public health problem. Particularly, the number of cases and fatality rates of ageing-associated diabetes increase with population ageing. This study aimed to investigate the structural characterisation of Ulva lactuca polysaccharide (ULP) and the hypoglycaemic effect on ageing-associated diabetic mice using gut microbiota variation. Sugar residuals analysis showed that the purified ULP (ULP-1) comprised β-D-Xylp-(1→3)-β-D-Arap-(1→6)-β-D-Galp-(1→6)-β-D-Glcp linked to [→α-L-Rhap-(1→4)-β-D-GlcpA→] and α-D-Manp-(1→4)-α-L-Rhap(2SO)-(1→2)-α-L-Rhap(4SO)-(1→2)-α-L-Arap-(1→2)-α-L-Rhap-(1→ as its side chains at β-D-Glcp. Moreover, ULP modulated the expression levels of p16, MMP2, FoxO1, GLP-1/GLP-1R, STAT3, and GLUT4 to improve the status of ageing and diabetes, which was concurrent with the increased abundance of Dubosiella, Enterococcus, Romboutsia, Bifidobacterium, Kurthia, Clostridium_sensu_stricto_1, Corynebacterium, Faecalibaculum, Aerococcus and Vibrio. Notably, Dubosiella, Romboutsia, Bifidobacterium, Turicibacter and Clostridium_sensu_stricto_1 could serve as important intermediates for delaying ageing and diabetes. Additionally, the ULP-1 structure is strongly binding interaction with the target protein through hydrogen bonding and Van der Waals force, especially for GLP-1 (-10.34 kcal/mol), p16 (-10.51 kcal/mol) and GLP-1R (-8.57 kcal/mol). Moreover, the average length of the hydrogen bond was observed to be 2.36 MPa, which is smaller than that of the traditional hydrogen bond. Therefore, ULP has the potential to function as a nutraceutical to delay or prevent the development of ageing-related type 2 diabetes.

Shakour, Z. T., and M. A. Farag, "Diverse host-associated fungal systems as a dynamic source of novel bioactive anthraquinones in drug discovery: Current status and future perspectives.", Journal of advanced research, vol. 39, pp. 257-273, 2022. Abstract

BACKGROUND: Despite, a large number of bioactive anthraquinones (AQs) isolated from host-living fungi, only plant-derived AQs were introduced in the global consumer markets. Host-living fungi represents renewable and extendible resources of diversified metabolites to be exploited for bioactives production. Unique classes of AQs from fungi include halogenated and steroidal AQs, and absent from planta are of potential to explore for biological activity against urging diseases such as cancer and multidrug-resistant pathogens. The structural diversity of fungal AQs, monomers, dimers, trimers, halogenated, etc… results in a vast range of pharmacological activities.

AIM OF REVIEW: The current study capitalizes on uncovering the diversity and distribution of host-living fungal systems producing AQs in different terrestrial ecosystems ranging from plant endophytes, lichens, animals and insects. Furthermore, the potential bioactivities of fungal derived AQs i.e., antibacterial, antifungal, antiviral (anti-HIV), anticancer, antioxidant, diuretic and laxative activities are assembled in relation to their structure activity relationship (SAR). Analyzing for structure-activity relationship among fungal AQs may facilitate bioengineering of more potential analogues. Withal, elucidation of AQs biosynthetic pathways in fungi is discussed from different fungal hosts to open up new possibilities for potential biotechnological applications. Such comprehensive review unravels terrestrial host-living fungal systems as a treasure trove in drug discovery, in addition to future perspectives and trends for their exploitation in pharmaceutical industries.

KEY SCIENTIFIC CONCEPTS OF REVIEW: Such comprehensive review unravels terrestrialhost-living fungal systems as a treasure trove in drug discovery, in addition to future perspectives and trends for their exploitation in pharmaceutical industries.

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