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.

Farag, M. A., S. E. Khaled, Z. El Gingeehy, S. N. Shamma, and A. Zayed, "Comparative Metabolite Profiling and Fingerprinting of Medicinal Cinnamon Bark and Its Commercial Preparations via a Multiplex Approach of GC-MS, UV, and NMR Techniques.", Metabolites, vol. 12, issue 7, 2022. Abstract

Various species of cinnamon ( sp.) are consumed as traditional medicine and popular spice worldwide. The current research aimed to provide the first comparative metabolomics study in nine cinnamon drugs and their different commercial preparations based on three analytical platforms, i.e., solid-phase microextraction coupled to gas chromatography-mass spectrometry method (SPME/GC-MS), nuclear magnetic resonance (NMR), and ultraviolet-visible spectrophotometry (UV/Vis) targeting its metabolome. SPME/GC-MS of cinnamon aroma compounds showed a total of 126 peaks, where ()-cinnamaldehyde was the major volatile detected at 4.2-60.9% and 6.3-64.5% in authenticated and commercial preparations, respectively. Asides, modeling of the GC/MS dataset could relate the commercial products CP-1 and CP-3 to attributed to their higher coumarin and low ()-cinnamaldehyde content. In contrast, NMR fingerprinting identified ()-methoxy cinnamaldehyde and coumarin as alternative markers for and , respectively. Additionally, quantitative NMR (qNMR) standardized cinnamon extracts based on major metabolites. UV/Vis showed to be of low discrimination power, but its orthogonal projections to latent structures discriminant analysis (OPLS-DA) S-plot showed that was more abundant in cinnamic acid compared to other samples. Results of this study provide potential insights into cinnamon drugs QC analysis and identify alternative markers for their discrimination.

Chen, Y., W. Wu, X. Ni, M. A. Farag, E. Capanoglu, and C. Zhao, "Regulatory mechanisms of the green alga oligosaccharide via the metabolomics and gut microbiome in diabetic mice.", Current research in food science, vol. 5, pp. 1127-1139, 2022. Abstract

Type 2 diabetes (T2D) has emerged as one of the most acute public health diseases of the present time, which increases with the population ageing. This study aimed to evaluate the hypoglycaemic activity of oligosaccharide (ULO) under ageing-related diabetes conditions in an animal model. The results demonstrated that ULO can promote hypoglycaemia and delay senescence as mediated GLP-1/GLP-1R pathway to mobilize the intercommunication between the brain and gut. In addition, twenty-six different metabolites and eight different bacteria were screened in the brain and the gut, respectively. A network relationship displayed that all-trans-retinoic acid has positive relationships with and , suggesting that plays a potential key role in maintaining the hypoglycaemic and anti-ageing activities of ULO. Based on these findings, ULO might be an efficient therapy for restoring blood glucose metabolism and delaying brain senescence in elderly T2D patients.

Farag, M. A., A. AbdelWareth, A. Zayed, T. F. Eissa, E. Dokalahy, A. Frolov, and L. A. Wessjohann, "A Comparative Metabolomics Approach for Egyptian Mango Fruits Classification Based on UV and UPLC/MS and in Relation to Its Antioxidant Effect.", Foods (Basel, Switzerland), vol. 11, issue 14, 2022. Abstract

Mango ( L.) is a tropical climacteric fruit that encompasses a myriad of metabolites mediating for its nutritive value, unique taste, flavor, and medicinal uses. Egypt is among the top mango producers worldwide, albeit little characterization has been made toward its fruits' chemical composition. This study aims to assess metabolites difference via comparative profiling and fingerprinting of Egyptian mango in context to its cultivar (cv.) type and/or growth province. To achieve such goal, hyphenated chromatographic techniques (UPLC/MS) and UV spectroscopy were employed and coupled to multivariate data analysis for Egyptian mango fruits' classification for the first time. UPLC/MS led to the detection of a total of 47 peaks identified based on their elution times and MS data, belonging to tannins as gallic acid esters, flavonoids, xanthones, phenolic acids and oxylipids. UV/Vis spectra of mango fruits showed similar absorption patterns mostly attributed to the phenolic metabolites, i.e., gallic acid derivatives and phenolic acids showing λ at ca. 240 and 270 nm. Modeling of both UPLC/MS and UV data sets revealed that cv. effect predominated over geographical origin in fruits segregation. Awees (AS) cv. showed the richest phenolic content and in agreement for its recognition as a premium cv. of mango in Egypt. Results of total phenolic content (TPC) assay revealed that AS was the richest in TPC at 179.1 mg GAE/g extract, while Langara from Ismailia (LI) showed the strongest antioxidant effect at 0.41 mg TE/g extract. Partial least square modeling of UV fingerprint with antioxidant action annotated gallates as potential contributor to antioxidant effect though without identification of exact moieties based on UPLC/MS. The study is considered the first-time investigation of Egyptian mango to aid unravel phytoconstituents responsible for fruits benefits using a metabolomics approach.

Eid, S. M., S. El-Shamy, and M. A. Farag, "Identification of milk quality and adulteration by surface-enhanced infrared absorption spectroscopy coupled to artificial neural networks using citrate-capped silver nanoislands.", Mikrochimica acta, vol. 189, issue 8, pp. 301, 2022. Abstract

Milk is one of the most important multicomponent superfoods owing to its rich macronutrient composition. It requires quality control at all the production stages from the farm to the finished products. A localized surface plasmon resonance optical sensor based on a citrate-capped silver nanoparticle (Cit-AgNP)-coated glass substrate was developed. The fabrication of such sensors involved a single-step synthesis of Cit-AgNPs followed by surface modification of glass slides to be coated with the nanoparticles. The scanning electron microscope micrographs demonstrated that the nanoparticles formed monolayer islands on glass slides. The developed surface-enhanced infrared absorption spectroscopy (SEIRA) sensor was coupled to artificial neural networking (ANN) for the qualitative differentiation between cow, camel, goat, buffalo, and infants' formula powdered milk types. Moreover, it can be used for the quantitative determination of the main milk components such as fat, casein, urea, and lactose in each milk type. The qualitative results showed that the obtained FTIR spectra of cow and buffalo milk have high similarity, whereas camel milk resembled infant formula powdered milk. The most difference in FTIR characteristics was evidenced in the case of goat milk. The developed sensor adds several advantages over the traditional techniques of milk analysis using MilkoScan™ such as less generated waste, elimination of pre-treatment steps, minimal sample volume, low operation time, and on-site analysis.

Baky, M. H., H. Fahmy, and M. A. Farag, "Recent Advances in Nutraceuticals in Relation to Its Hydroxy Citric Acid Level. A Comprehensive Review of Its Bioactive Production, Formulation, and Analysis with Future Perspectives.", ACS omega, vol. 7, issue 30, pp. 25948-25957, 2022. Abstract

(Gaertn.) Desr. (known as Malabar tamarind) is a popular traditional herbal medicine and is one of the well-known folk medicines reported for the treatment of obesity and incorporated in several nutraceuticals worldwide. These effects are mediated by a myriad of bioactive compounds with most effects attributed to its hydroxy citric acid (HCA) content. This review aims to present a holistic overview on novel trends in the production of . bioactive components and how extraction optimization is important to ensure best product quality with its reported nanoformulations with particular emphasis on HCA content. Further, an overview of the different analytical approaches used for quality control assessment of . plant and its nutraceuticals is presented highlighting both advantages and limitations. Moreover, analytical approaches for detecting . metabolites in biological fluids with emphasis on HCA level to determine its pharmacokinetics and proof of efficacy are presented for the first time.