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2018
Elmassry, M. M., L. Kormod, R. M. Labib, and M. A. Farag, "Metabolome based volatiles mapping of roasted umbelliferous fruits aroma via HS-SPME GC/MS and peroxide levels analyses.", Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, vol. 1099, pp. 117-126, 2018 Nov 01. Abstract

Despite studies on umbelliferous fruits flavor makeup, nothing is known regarding roasting impact on their fruit aroma. Five major umbelliferous crops viz., anise, caraway, coriander, cumin and fennel were analyzed via headspace solid-phase microextraction to reveal for 117 volatile constituents. Oxygenated monoterpenes amounted for the major volatile class in raw fruits at 75% with (E)-anethole, carvone, β-linalool, cuminaldehyde and estragole as major components in anise, caraway, coriander, cumin, and fennel, respectively. Difference was observed in fennel fruit "estragole" levels derived from different origins. Upon roasting, several novel volatiles were detected viz. pyrazines and flavored Milliard type volatiles. Major flavor intensified response was detected in cumin with an increase in its "cuminaldehyde" levels versus a decrease of estragole levels in fennel. Roasted cumin exhibited highest peroxide value 14.2 mEq O/Kg, whereas the least was detected in fennel at 6.1 mEq O/Kg, though with both values not representing a health hazard.

Rasheed, D. M., A. Porzel, A. Frolov, H. R. El Seedi, L. A. Wessjohann, and M. A. Farag, "Comparative analysis of Hibiscus sabdariffa (roselle) hot and cold extracts in respect to their potential for α-glucosidase inhibition.", Food chemistry, vol. 250, pp. 236-244, 2018 Jun 01. Abstract

Roselle (Hibiscus sabdariffa) is a functional food with potential health benefits, consumed either as hot or cold beverage. To ensure quality control of its various products, accurate measurement of active metabolites is warranted. Herein, we propose a combination of ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and nuclear magnetic resonance (NMR) analytical platforms for the untargeted characterization of metabolites in two roselle cultivars, Aswan and Sudan-1. The analyses revealed 33 metabolites, including sugars, flavonoids, anthocyanins, phenolic and aliphatic organic acids. Their relative contents in cultivars were assessed via principle component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS). Impact of the different extraction methods (decoction, infusion and maceration) was compared by quantitative H NMR spectroscopy, revealing cold maceration to be optimal for preserving anthocyanins, whereas infusion was more suited for recovering organic acids. The metabolite pattern revealed by the different extraction methods was found in good correlation for their ability to inhibit α-glucosidase enzyme.

Farag, M. A., A. Meyer, S. E. Ali, M. A. Salem, P. Giavalisco, H. Westphal, and L. A. Wessjohann, "Comparative Metabolomics Approach Detects Stress-Specific Responses during Coral Bleaching in Soft Corals.", Journal of proteome research, vol. 17, issue 6, pp. 2060-2071, 2018 Jun 01. Abstract

Chronic exposure to ocean acidification and elevated sea-surface temperatures pose significant stress to marine ecosystems. This in turn necessitates costly acclimation responses in corals in both the symbiont and host, with a reorganization of cell metabolism and structure. A large-scale untargeted metabolomics approach comprising gas chromatography mass spectrometry (GC-MS) and ultraperformance liquid chromatography coupled to high resolution mass spectrometry (UPLC-MS) was applied to profile the metabolite composition of the soft coral Sarcophyton ehrenbergi and its dinoflagellate symbiont. Metabolite profiling compared ambient conditions with response to simulated climate change stressors and with the sister species, S. glaucum. Among ∼300 monitored metabolites, 13 metabolites were modulated. Incubation experiments providing four selected upregulated metabolites (alanine, GABA, nicotinic acid, and proline) in the culturing water failed to subside the bleaching response at temperature-induced stress, despite their known ability to mitigate heat stress in plants or animals. Thus, the results hint to metabolite accumulation (marker) during heat stress. This study provides the first detailed map of metabolic pathways transition in corals in response to different environmental stresses, accounting for the superior thermal tolerance of S. ehrenbergi versus S. glaucum, which can ultimately help maintain a viable symbiosis and mitigate against coral bleaching.

El-Seedi, H. R., S. A. M. Khalifa, E. A. Taher, M. A. Farag, A. Saeed, M. Gamal, M. - E. F. Hegazy, D. Youssef, S. G. Musharraf, M. M. Alajlani, et al., "Cardenolides: Insights from chemical structure and pharmacological utility.", Pharmacological research, vol. 141, pp. 123-175, 2018 Dec 21. Abstract

Cardiac glycosides (CGs) are a class of naturally occurring steroid-like compounds, and members of this class have been in clinical use for more than 1500 years. They have been used in folk medicine as arrow poisons, abortifacients, heart tonics, emetics, and diuretics as well as in other applications. The major use of CGs today is based on their ability to inhibit the membrane-bound Na/K-ATPase enzyme, and they are regarded as an effective treatment for congestive heart failure (CHF), cardiac arrhythmia and atrial fibrillation. Furthermore, increasing evidence has indicated the potential cytotoxic effects of CGs against various types of cancer. In this review, we highlight some of the structural features of this class of natural products that are crucial for their efficacy, some methods of isolating these compounds from natural resources, and the structural elucidation tools that have been used. We also describe their physicochemical properties and several modern biotechnological approaches for preparing CGs that do not require plant sources.

Taleb, M. H., N. F. Abdeltawab, R. N. Shamma, S. S. Abdelgayed, S. S. Mohamed, M. A. Farag, and M. A. Ramadan, "L. Essential Oil as a Potential Anti-Acne Topical Nanoemulsion-In Vitro and In Vivo Study.", Molecules (Basel, Switzerland), vol. 23, issue 9, 2018 Aug 28. Abstract

Antibiotics are often prescribed in acne treatment; however, and , the two of the major acne-associated bacteria, developed antibiotic resistance. Essential oils (EOs) present a natural, safe, efficacious and multifunctional alternative treatment. This study aimed to assess the potential anti-acne activity of selected seven EOs commonly used in Mediterranean folk medicine. Antimicrobial activity screening of these oils showed oregano to exhibit the strongest antimicrobial activity with minimum inhibitory concentration (MIC) of 0.34 mg/mL and minimum bactericidal concentration (MBC) of 0.67 mg/mL against ; and MIC of 0.67 mg/mL and MBC of 1.34 mg/mL against . The composition of the most effective EOs (oregano and thyme) was determined using gas chromatography-mass spectrometry (GC-MS). Monoterpenoid phenols predominated oregano and thyme EO with thymol percentile 99 and 72, respectively. Thymol showed MIC 0.70 mg/mL against both and whereas MBC was 1.40 and 2.80 mg/mL against and , respectively. Moreover, oregano exhibited the strongest anti-biofilm effect against with MBIC 1.34 mg/mL and killing dynamic time of 12 and 8 h against and , respectively. Oregano, the most effective EO, was formulated and tested as a nanoemulsion in an acne animal mouse model. The formulation showed superior healing and antimicrobial effects compared to the reference antibiotic. Collectively, our data suggested that oregano oil nanoemulsion is a potential natural and effective alternative for treating acne and overcoming the emerging antibiotic resistance.

Farag, M. A., A. R. Khattab, A. Ehrlich, M. Kropf, A. G. Heiss, and L. A. Wessjohann, "Gas Chromatography/Mass Spectrometry-Based Metabolite Profiling of Nutrients and Antinutrients in Eight Lens and Lupinus Seeds (Fabaceae).", Journal of agricultural and food chemistry, vol. 66, issue 16, pp. 4267-4280, 2018 Apr 25. Abstract

Lens culinaris and several Lupinus species are two legumes regarded as potential protein resources aside from their richness in phytochemicals. Consequently, characterization of their metabolite composition seems warranted to be considered as a sustainable commercial functional food. This study presents a discriminatory holistic approach for metabolite profiling in accessions of four lentil cultivars and four Lupinus species via gas chromatography/mass spectrometry. A total of 107 metabolites were identified, encompassing organic and amino acids, sugars, and sterols, along with antinutrients, viz., alkaloids and sugar phosphates. Among the examined specimens, four nutritionally valuable accessions ought to be prioritized for future breeding to include Lupinus hispanicus, enriched in organic ( ca. 11.7%) and amino acids ( ca. 5%), and Lupinus angustifolius, rich in sucrose ( ca. 40%), along with two dark-colored lentil cultivars 'verte du Puy' and 'Black Beluga' enriched in peptides. Antinutrient chemicals were observed in Lupinus polyphyllus, owing to its high alkaloid content. Several species-specific markers were also revealed using multivariate data analyses.

Farag, M. A., N. m Fayek, and I. Abou Reidah, "Volatile profiling in fruit (sumac) from three different geographical origins and upon roasting as analyzed via solid-phase microextraction.", PeerJ, vol. 6, pp. e5121, 2018. Abstract

(sumac) is a fruit grown worldwide for its culinary use as a flavoring agent and for its health benefits. Despite several studies on non-volatile metabolites, much less is recognized concerning volatile composition within that genus. In an effort to expand on flavor profile sumac and its food products, we report on volatile profiling from three accessions of different origins including Palestine, Jordan and Egypt in addition to its cold tea and post roasting via headspace solid-phase microextraction (SPME). Under optimized conditions, 74 volatile components were identified belonging to alcohols, aromatics, esters, ethers, furan/aldehyde, hydrocarbons, ketones, monoterpenes, oxides and sesquiterpene hydrocarbons. Major identified components included α-pinene, naphthalene and o-cymene in Palestinian, Jordanian and Egyptian sumac, respectively. Whereas sesquiterpenes amounted for the major volatile class in fresh at ca. 40-58%, furan/aldehydes were the predominant classes in roasted fruits (58%). Volatile abundance data was further subjected to multivariate data analyses revealing furfural and nonanal enrichment in roasted compared to fresh fruits and their cold tea preparation. Seeds exhibited no aroma components which justified their removal in prior to its use as a food flavor. Such knowledge is expected to be the key for understanding the olfactory and taste properties of and its several food products.

2017
El-Seedi, H. R., M. Azeem, N. S. Khalil, H. H. Sakr, S. A. M. Khalifa, K. Awang, A. Saeed, M. A. Farag, M. F. AlAjmi, K. Pålsson, et al., "Essential oils of aromatic Egyptian plants repel nymphs of the tick Ixodes ricinus (Acari: Ixodidae).", Experimental & applied acarology, vol. 73, issue 1, pp. 139-157, 2017 Sep. Abstract

Due to the role of Ixodes ricinus (L.) (Acari: Ixodidae) in the transmission of many serious pathogens, personal protection against bites of this tick is essential. In the present study the essential oils from 11 aromatic Egyptian plants were isolated and their repellent activity against I. ricinus nymphs was evaluated Three oils (i.e. Conyza dioscoridis L., Artemisia herba-alba Asso and Calendula officinalis L.) elicited high repellent activity in vitro of 94, 84.2 and 82%, respectively. The most active essential oil (C. dioscoridis) was applied in the field at a concentration of 6.5 µg/cmand elicited a significant repellent activity against I. ricinus nymphs by 61.1%. The most repellent plants C. dioscoridis, C. officinalis and A. herba-alba yielded essential oils by 0.17, 0.11 and 0.14%, respectively. These oils were further investigated using gas chromatography-mass spectrometry analysis. α-Cadinol (10.7%) and hexadecanoic acid (10.5%) were the major components of C. dioscoridis whereas in C. officinalis, α-cadinol (21.2%) and carvone (18.2%) were major components. Artemisia herba-alba contained piperitone (26.5%), ethyl cinnamate (9.5%), camphor (7.7%) and hexadecanoic acid (6.9%). Essential oils of these three plants have a potential to be used for personal protection against tick bites.

Farag, M. A., S. E. Ali, R. H. Hodaya, H. R. El-Seedi, H. N. Sultani, A. Laub, T. F. Eissa, F. O. F. Abou-Zaid, and L. A. Wessjohann, "Phytochemical Profiles and Antimicrobial Activities of Allium cepa Red cv. and A. sativum Subjected to Different Drying Methods: A Comparative MS-Based Metabolomics.", Molecules (Basel, Switzerland), vol. 22, issue 5, 2017 May 08. Abstract

Plants of thegenus produce sulphur compounds that give them a characteristic (alliaceous) flavour and mediate for their medicinal use. In this study, the chemical composition and antimicrobial properties ofred cv. andin the context of three different drying processes were assessed using metabolomics. Bulbs were dried using either microwave, air drying, or freeze drying and further subjected to chemical analysis of their composition of volatile and non-volatile metabolites. Volatiles were collected using solid phase micro-extraction (SPME) coupled to gas chromatography-mass spectrometry (GC/MS) with 42 identified volatiles including 30 sulphur compounds, four nitriles, three aromatics, and three esters. Profiling of the polar non-volatile metabolites via ultra-performance liquid chromatography coupled to high resolution MS (UPLC/MS) annotated 51 metabolites including dipeptides, flavonoids, phenolic acids, and fatty acids. Major peaks in GC/MS or UPLC/MS contributing to the discrimination betweenandred cv. were assigned to sulphur compounds and flavonoids. Whereas sulphur conjugates amounted to the major forms in, flavonoids predominated in the chemical composition ofred cv. With regard to drying impact onmetabolites, notable and clear separations among specimens were revealed using principal component analysis (PCA). The PCA scores plot of the UPLC/MS dataset showed closer metabolite composition of microwave dried specimens to freeze dried ones, and distant from air dried bulbs, observed in bothand. Compared to GC/MS, the UPLC/MS derived PCA model was more consistent and better in assessing the impact of drying onmetabolism. A phthalate derivative was found exclusively in a commercial garlic preparation via GC/MS, of yet unknown origin. The freeze dried samples of bothspecies exhibited stronger antimicrobial activities compared to dried specimens withbeing in general more active thanred cv.

Farag, M. A., N. M. Ammar, T. E. Kholeif, N. S. Metwally, N. M. El-Sheikh, L. A. Wessjohann, and A. Z. Abdel-Hamid, "Rats' urinary metabolomes reveal the potential roles of functional foods and exercise in obesity management.", Food & function, vol. 8, issue 3, pp. 985-996, 2017 Mar 22. Abstract

The complexity of the metabolic changes in obese individuals still presents a challenge for the understanding of obesity-related metabolic disruptions and for obesity management. In this study, a gas chromatography mass spectrometry (GC-MS) based metabolomics approach targeting urine metabolism has been applied to assess the potential roles of functional foods and exercise for obesity management in rats. Male albino rats diagnosed as obese via histopathology and biochemical assays were administered functional foods in common use for obesity management including pomegranate, grapefruit, and red cabbage juice extracts in parallel with swimming exercise. Urine samples were collected from these rats, and likewise from healthy control animals, for metabolite analysis using (GC-MS) coupled to multivariate data analysis. The results revealed a significant elevation in oxalate and phosphate levels in obese rat urine concurrent with lower lactate levels as compared to the control group. Furthermore, and to pinpoint the bioactive agents in the administered functional foods, ultra performance liquid chromatography (UPLC) coupled to high resolution time-of-flight mass spectrometry (TOF-MS) was employed for secondary metabolite profiling. The different phenolic classes found in the examined functional foods, viz. ellagitannins in pomegranate, flavanones in grapefruit and flavonols in red cabbage, are likely to mediate their anti-obesity effects. The results indicate that these functional foods and exercise were quite effective in reverting obesity-related metabolic disruptions back to normal status, as revealed by orthogonal partial least squares-discriminant analysis (OPLS-DA).

Farag, M. A., M. I. Fekry, M. A. Al-Hammady, M. N. Khalil, H. R. El-Seedi, A. Meyer, A. Porzel, H. Westphal, and L. A. Wessjohann, "Cytotoxic Effects of Sarcophyton sp. Soft Corals-Is There a Correlation to Their NMR Fingerprints?", Marine drugs, vol. 15, issue 7, 2017 Jul 04. Abstract

sp. soft corals are rich in cembranoid diterpenes, which represent the main chemical defense of corals against their natural predators in addition to their myriad biological effects in humans. Quantitative NMR (qNMR) was applied for assessing the diterpene variation in 16 soft coral specimens in the context of their genotype, origin, and growing habitat. qNMR revealed high diterpene levels insp. compared toand, with (ent)sarcophines as major components (17-100 µg/mg) of the coral tissues. Multivariate data analysis was employed to classify samples based on the quantified level of diterpenes, and compared to the untargeted NMR approach. Results revealed that qNMR provided a stronger classification model ofsp. than untargeted NMR fingerprinting. Additionally, cytotoxicity of soft coral crude extracts was assessed against androgen-dependent prostate cancer cell lines (PC3) and androgen-independent colon cancer cell lines (HT-29), with ICvalues ranging from 10-60 µg/mL. No obvious correlation between the extracts' ICvalues and their diterpene levels was found using either Spearman or Pearson correlations. This suggests that this type of bioactivity may not be easily predicted by NMR metabolomics in soft corals, or is not strongly correlated to measured diterpene levels.

Farag, M. A., G. C. Song, Y. - S. Park, B. Audrain, S. Lee, J. - M. Ghigo, J. W. Kloepper, and C. - M. Ryu, "Biological and chemical strategies for exploring inter- and intra-kingdom communication mediated via bacterial volatile signals.", Nature protocols, vol. 12, issue 7, pp. 1359-1377, 2017 Jul. Abstract

Airborne chemical signals emitted by bacteria influence the behavior of other bacteria and plants. We present an overview of in vitro methods for evaluating bacterial and plant responses to bacterial volatile compounds (BVCs). Three types of equipment have been used to physically separate the bacterial test strains from either other bacterial strains or plants (in our laboratory we use either Arabidopsis or tobacco plant seedlings): a Petri dish containing two compartments (BI Petri dish); two Petri dishes connected with tubing; and a microtiter-based assay. The optimized procedure for the BI Petri dish system is described in this protocol and can be widely used for elucidation of potential function in interactions between diverse microbes and those plant and chemical volatiles emitted by bacteria that are most likely to mediate bacterial or plant responses to BVCs. We also describe a procedure for metabolome-based BVC profiling via dynamic (i.e., continuous airflow) or static headspace sampling using solid-phase microextraction (SPME). Using both these procedures, bacteria-bacteria communications and bacteria-plant interactions mediated by BVCs can be rapidly investigated (within 1-4 weeks).

Farag, M. A., and D. M. El-Kersh, "Volatiles profiling in(Carob bean) from Egypt and in response to roasting as analyzedsolid-phase microextraction coupled to chemometrics.", Journal of advanced research, vol. 8, issue 4, pp. 379-385, 2017 Jul. Abstract

is a legume tree of considerable commercial importance for the flavor and sweets industry cultivated mostly for its pods nutritive value and or several health benefits. Despite extensive studies onpod non-volatile metabolites, much less is known regarding volatiles composition which contributes to the flavor of its many food products. To gain insight intoaroma, 31 volatile constituents from unroasted and roasted pods were profiled using headspace solid-phase micro extraction (HD-SPME) analyzedquadruple mass spectrometer followed by multivariate data analyses. Short chain fatty acids amounted for the major volatile class at. (71-77%) with caproic acid (20%) and pentanoic acid (15-25%) as major components. Compared to ripe pod, roasted ripe pod was found less enriched in major volatile classes., short chain fatty acids and aldehydes, except for higher pyranone levels. Volatiles mediating for unheated and hot carob fruit aroma is likely to be related to its ()-cinnamaldehyde and pyranone content, respectively. Such knowledge is expected to be the key for understanding the olfactory and taste properties ofand its various commercial food products.

Farag, M. A., S. A. Fahmy, M. A. Choucry, M. O. Wahdan, and M. F. Elsebai, "Metabolites profiling reveals for antimicrobial compositional differences and action mechanism in the toothbrushing stick "miswak" Salvadora persica.", Journal of pharmaceutical and biomedical analysis, vol. 133, pp. 32-40, 2017 Jan 30. Abstract

Among many plant species suitable for preparing toothbrushing sticks, miswak (Salvadora persica, family Salvadoraceae) is found the most effective tool for oral hygiene. S. persica possesses antibacterial, antiviral and antifungal effects against oral microbes, mostly due to its benzyl isothiocyanate content. To provide insight into S. persica chemical composition, volatile constituents from roots and stems of S. persica grown in Egypt and Saudi Arabia were profiled using solid-phase microextraction (SPME) coupled to gas chromatography-mass spectrometry (GC-MS). A total of 21 volatiles were identified with sulfur compounds amounting for the major volatile class. Orthogonal projection to latent structures-discriminant analysis (OPLS-DA) revealed for benzyl isothiocyanate (BITC) enrichment in roots versus stems. Primary metabolites contributing to S. persica taste viz. sugars and organic acids were profiled using GC-MS with silylation. Polyols (sugars) viz. arabitol, meso-erythritol, and mannitol were found to predominate sugars composition in S. persica stems being most enriched in meso-erythritol. The impact of saliva on S. persica aroma profile was further assessed and revealing for no enhancement in BITC production with salivation, and further not being detected in toothpaste preparation claimed to contain S. persica extract. This study provides the most complete profile of volatiles, sugars, and organic acids in S. persica organs and more rationalizing its use as a toothbrush.

Ibrahim, S. R. M., H. M. Abdallah, G. A. Mohamed, M. A. Farag, K. Z. Alshali, E. A. Alsherif, and S. A. Ross, "Volatile oil profile of some lamiaceous plants growing in Saudi Arabia and their biological activities.", Zeitschrift fur Naturforschung. C, Journal of biosciences, vol. 72, issue 1-2, pp. 35-41, 2017 Jan 01. Abstract

A comparative investigation of hydro-distilled essential oils from aerial parts of Mentha longifolia L. (ML), Mentha microphylla K.Koch (MM), Mentha australis R.Br. (MA), and Teucrium polium L. (TP) growing in Al Madinah Al Munawwarah, Saudi Arabia, was carried out. The total numbers of identified constituents were 22, 23, 14, and 20 in ML, MM, MA, and TP oils, representing 93.0, 99.3, 78.1, and 81.1% of the total oil composition, respectively. Pulegone (40.7%) and cineole (33.4%) were the major components in ML, whereas carvone (64.6%) was the major one in MM. Furthermore, β-linalool (22.9%) and α-terpineol (12%) were the major components in MA, whereas, (E)-3-caren-2-ol accounted for 12.1% in TP. The essential oils of TP and MA exhibited promising activities against Leishmania donovani promastigotes with IC50 values of 2.3 and 3.7 μg/mL, respectively. In contrast, MA essential oils exhibited antifungal activities towards Candida krusei and C. glabrata with IC50 values of 1 and 1.2 μg/mL, respectively.

Ibrahim, S. R. M., H. M. Abdallah, G. A. Mohamed, M. A. Farag, K. Z. Alshali, E. A. Alsherif, and S. A. Ross, "Volatile oil profile of some lamiaceous plants growing in Saudi Arabia and their biological activities.", Zeitschrift fur Naturforschung. C, Journal of biosciences, vol. 72, issue 1-2, pp. 35-41, 2017 Jan 01. Abstractfarag_et_al_j_naturforsch_2017.pdf

A comparative investigation of hydro-distilled essential oils from aerial parts of Mentha longifolia L. (ML), Mentha microphylla K.Koch (MM), Mentha australis R.Br. (MA), and Teucrium polium L. (TP) growing in Al Madinah Al Munawwarah, Saudi Arabia, was carried out. The total numbers of identified constituents were 22, 23, 14, and 20 in ML, MM, MA, and TP oils, representing 93.0, 99.3, 78.1, and 81.1% of the total oil composition, respectively. Pulegone (40.7%) and cineole (33.4%) were the major components in ML, whereas carvone (64.6%) was the major one in MM. Furthermore, β-linalool (22.9%) and α-terpineol (12%) were the major components in MA, whereas, (E)-3-caren-2-ol accounted for 12.1% in TP. The essential oils of TP and MA exhibited promising activities against Leishmania donovani promastigotes with IC50 values of 2.3 and 3.7 μg/mL, respectively. In contrast, MA essential oils exhibited antifungal activities towards Candida krusei and C. glabrata with IC50 values of 1 and 1.2 μg/mL, respectively.

Ibrahim, S. R. M., H. M. Abdallah, G. A. Mohamed, M. A. Farag, K. Z. Alshali, E. A. Alsherif, and S. A. Ross, "Volatile oil profile of some lamiaceous plants growing in Saudi Arabia and their biological activities.", Zeitschrift fur Naturforschung. C, Journal of biosciences, vol. 72, issue 1-2, pp. 35-41, 2017 Jan 01. Abstractfarag_et_al_j_naturforsch_2017.pdf

A comparative investigation of hydro-distilled essential oils from aerial parts of Mentha longifolia L. (ML), Mentha microphylla K.Koch (MM), Mentha australis R.Br. (MA), and Teucrium polium L. (TP) growing in Al Madinah Al Munawwarah, Saudi Arabia, was carried out. The total numbers of identified constituents were 22, 23, 14, and 20 in ML, MM, MA, and TP oils, representing 93.0, 99.3, 78.1, and 81.1% of the total oil composition, respectively. Pulegone (40.7%) and cineole (33.4%) were the major components in ML, whereas carvone (64.6%) was the major one in MM. Furthermore, β-linalool (22.9%) and α-terpineol (12%) were the major components in MA, whereas, (E)-3-caren-2-ol accounted for 12.1% in TP. The essential oils of TP and MA exhibited promising activities against Leishmania donovani promastigotes with IC50 values of 2.3 and 3.7 μg/mL, respectively. In contrast, MA essential oils exhibited antifungal activities towards Candida krusei and C. glabrata with IC50 values of 1 and 1.2 μg/mL, respectively.

Ibrahim, S. R. M., H. M. Abdallah, G. A. Mohamed, M. A. Farag, K. Z. Alshali, E. A. Alsherif, and S. A. Ross, "Volatile oil profile of some lamiaceous plants growing in Saudi Arabia and their biological activities.", Zeitschrift fur Naturforschung. C, Journal of biosciences, vol. 72, issue 1-2, pp. 35-41, 2017 Jan 01. Abstractfarag_et_al_j_naturforsch_2017.pdf

A comparative investigation of hydro-distilled essential oils from aerial parts of Mentha longifolia L. (ML), Mentha microphylla K.Koch (MM), Mentha australis R.Br. (MA), and Teucrium polium L. (TP) growing in Al Madinah Al Munawwarah, Saudi Arabia, was carried out. The total numbers of identified constituents were 22, 23, 14, and 20 in ML, MM, MA, and TP oils, representing 93.0, 99.3, 78.1, and 81.1% of the total oil composition, respectively. Pulegone (40.7%) and cineole (33.4%) were the major components in ML, whereas carvone (64.6%) was the major one in MM. Furthermore, β-linalool (22.9%) and α-terpineol (12%) were the major components in MA, whereas, (E)-3-caren-2-ol accounted for 12.1% in TP. The essential oils of TP and MA exhibited promising activities against Leishmania donovani promastigotes with IC50 values of 2.3 and 3.7 μg/mL, respectively. In contrast, MA essential oils exhibited antifungal activities towards Candida krusei and C. glabrata with IC50 values of 1 and 1.2 μg/mL, respectively.

Khalil, M. N. A., M. I. Fekry, and M. A. Farag, "Metabolome based volatiles profiling in 13 date palm fruit varieties from Egypt via SPME GC-MS and chemometrics.", Food chemistry, vol. 217, pp. 171-181, 2017 Feb 15. Abstract

Dates (Phoenix dactylifera L.) are distributed worldwide as major food complement providing a source of sugars and dietary fiber as well as macro- and micronutrients. Although phytochemical analyses of date fruit non-volatile metabolites have been reported, much less is known about the aroma given off by the fruit, which is critical for dissecting sensory properties and quality traits. Volatile constituents from 13 date varieties grown in Egypt were profiled using SPME-GCMS coupled to multivariate data analysis to explore date fruit aroma composition and investigate potential future uses by food industry. A total of 89 volatiles were identified where lipid-derived volatiles and phenylpropanoid derivatives were the major components of date fruit aroma. Multivariate data analyses revealed that 2,3-butanediol, hexanal, hexanol and cinnamaldehyde contributed the most to classification of different varieties. This study provides the most complete map of volatiles in Egyptian date fruit, with Siwi and Sheshi varieties exhibiting the most distinct aroma among studied date varieties.

Amavizca, E., Y. Bashan, C. - M. Ryu, M. A. Farag, B. M. Bebout, and L. E. de-Bashan, "Enhanced performance of the microalga Chlorella sorokiniana remotely induced by the plant growth-promoting bacteria Azospirillum brasilense and Bacillus pumilus.", Scientific reports, vol. 7, pp. 41310, 2017 Feb 01. Abstract

Remote effects (occurring without physical contact) of two plant growth-promoting bacteria (PGPB) Azospirillum brasilense Cd and Bacilus pumilus ES4 on growth of the green microalga Chlorella sorokiniana UTEX 2714 were studied. The two PGPB remotely enhanced the growth of the microalga, up to six-fold, and its cell volume by about three-fold. In addition to phenotypic changes, both bacteria remotely induced increases in the amounts of total lipids, total carbohydrates, and chlorophyll a in the cells of the microalga, indicating an alteration of the microalga's physiology. The two bacteria produced large amounts of volatile compounds, including CO, and the known plant growth-promoting volatile 2,3-butanediol and acetoin. Several other volatiles having biological functions in other organisms, as well as numerous volatile compounds with undefined biological roles, were detected. Together, these bacteria-derived volatiles can positively affect growth and metabolic parameters in green microalgae without physical attachment of the bacteria to the microalgae. This is a new paradigm on how PGPB promote growth of microalgae which may serve to improve performance of Chlorella spp. for biotechnological applications.

Farag, M. A., H. Westphal, T. F. Eissa, L. A. Wessjohann, and A. Meyer, "Effect of Oxylipins, Terpenoid Precursors and Wounding on Soft Corals' Secondary Metabolism as Analyzed via UPLC/MS and Chemometrics.", Molecules (Basel, Switzerland), vol. 22, issue 12, 2017 Dec 10. Abstractfarag_et_al._molecules__2_2017.pdf

The effect of three oxylipin analogues, a terpenoid intermediate and wounding on the secondary metabolism of the soft coralsandwas assessed. Examined oxylipins included prostaglandin (PG-E1), methyl jasmonate (MeJA), and arachidonic acid (AA) in addition to the diterpene precursor geranylgeranylpyrophosphate (GGP). Post-elicitation, metabolites were extracted from coral heads and analyzed via UPLC-MS followed by multivariate data analyses. Both supervised and unsupervised data analyses were used for sample classification. Multivariate data analysis revealed clear segregation of PG-E1 and MeJA elicitedat 24 and 48 h post elicitation from other elicitor samples and unelicited control group. PG-E1 was found more effective in upregulatingterpene/sterol levels compared to MeJA. Metabolites showing upregulation ininclude campestene-triol and a cembranoid, detected at ca. 30- and 2-fold higher levels compared to unelicited corals. Such an elicitation effect was less notable in the other coral speciessuggesting a differential oxylipin response in soft corals. Compared to MeJA and PG, no elicitation effect was observed for GGP, AA or wounding on the metabolism of either coral species.

Ammar, N. M., M. A. Farag, T. E. Kholeif, N. S. Metwally, N. M. El-Sheikh, A. N. El Gendy, and A. - H. Z. Abdel-Hamid, "Serum metabolomics reveals the mechanistic role of functional foods and exercise for obesity management in rats.", Journal of pharmaceutical and biomedical analysis, vol. 142, pp. 91-101, 2017 Aug 05. Abstract

Obesity is one of the independent risk factors for several health problems, leading to metabolic perturbations and for which analytical approaches i.e., "metabolomics" is needed to monitor the underlying metabolic changes. In this study, obesity associated changes were assessed via serum metabolites analysis of obese rats fed on high fat diet. Obese rats were subsequently treated with different functional foods used for obesity management including pomegranate, grapefruit, and red cabbage in parallel to swimming exercise. Serum samples were analyzed using gas chromatography-mass spectrometry (GC-MS) followed by multivariate data analysis to classify samples and determine if such treatments can help revert obesity related metabolic changes back to normal status. Results led to the identification of several novel metabolites biomarkers for obesity related to lipids, amino acids and central tricarboxylic acid (TCA) pathways. Distinct variations in metabolite levels were recorded in obese rats compared to normal ones including l-aspartic, l-alanine, l-glutamine, l-glycine, phenylethanolamine, α-aminobutyric acid and β-hydroxybutyric acid. Metabolomics approach developed herein provides novel insight onto the metabolic disturbances associated with obesity, which will assist in future drug design that can help mitigate against such changes.

Farag, M. A., D. A. Al-Mahdy, A. Meyer, H. Westphal, and L. A. Wessjohann, "Metabolomics reveals biotic and abiotic elicitor effects on the soft coral Sarcophyton ehrenbergi terpenoid content.", Scientific reports, vol. 7, issue 1, pp. 648, 2017 Apr 05. Abstract

The effects of six biotic and abiotic elicitors, i.e. MeJA (methyl jasmonate), SA (salicylic acid), ZnCl, glutathione and β-glucan BG (fungal elicitor), and wounding, on the secondary metabolite accumulation in the soft coral Sarcophyton ehrenbergi were assessed. Upon elicitation, metabolites were extracted and analysed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Except for MeJA, no differences in photosynthetic efficiency were observed after treatments, suggesting the absence of a remarkable stress on primary production. Chemometric analyses of UPLC-MS data showed clear segregation of SA and ZnClelicited samples at 24 and 48 h post elicitation. Levels of acetylated diterpene and sterol viz., sarcophytonolide I and cholesteryl acetate, was increased in ZnCland SA groups, respectively, suggesting an activation of specific acetyl transferases. Post elicitation, sarcophytonolide I level increased 132 and 17-folds at 48 h in 0.1 mM SA and 1 mM ZnClgroups, respectively. Interestingly, decrease in sarcophine, a major diterpene was observed only in response to ZnCl, whereas no change was observed in sesquiterpene content following treatments. To the best of our knowledge, this study provides the first documentation for elicitation effects on a soft corals secondary metabolome and suggests that SA could be applied to increase diterpenoid levels in corals.

Atteya, R., M. E. Ashour, E. E. Ibrahim, M. A. Farag, and S. F. El-Khamisy, "Chemical screening identifies the β-Carboline alkaloid harmine to be synergistically lethal with doxorubicin.", Mechanisms of ageing and development, vol. 161, issue Pt A, pp. 141-148, 2017 01. Abstract

Despite being an invaluable chemotherapeutic agent for several types of cancer, the clinical utility of doxorubicin is hampered by its age-related and dose-dependent cardiotoxicity. Co-administration of dexrazoxane as a cardioprotective agent has been proposed, however recent studies suggest that it attenuates doxorubicin-induced antitumor activity. Since compounds of natural origin present a rich territory for drug discovery, we set out to identify putative natural compounds with the view to mitigate or minimize doxorubicin cardiotoxicity. We identify the DYRK1A kinase inhibitor harmine, which phosphorylates Tau that is deregulated in Alzheimer's disease, as a potentiator of cell death induced by non-toxic doses of doxorubicin. These observations suggest that harmine or other compounds that target the DYRK1A kinase my offer a new therapeutic opportunity to suppress doxorubicin age-related and dose-dependent cardiotoxicity.

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