Metabolite Profiling of Colvillea racemosa via UPLC-ESI-QTOF-MS Analysis in Correlation to the In Vitro Antioxidant and Cytotoxic Potential against A549 Non-Small Cell Lung Cancer Cell Line.

In this study, flower and leaf extracts of Colvillea racemosa were considered a source of bioactive compounds. In this context, the objective of the study focused on investigating the anticancer potential as well as the phytochemical composition of both extracts. The extracts were analyzed by UPLC-ESI-QTOF-MS, and the bioactivity was tested using in vitro antioxidant assays (FRAP, DPPH, and ABTS) in addition to cytotoxic assays on non-small cell lung cancer cell line (A549). Our results clearly indicated the potent radical scavenging capacity of both extracts. Importantly, the flower extract exhibited a greater antioxidant capacity than the leaf extract. In terms of cytotoxic activity, leaf and flower extracts significantly inhibited cell viability with IC50 values of 17.0 and 17.2 µg/mL, respectively. The phytochemical characterization enabled the putative annotation of 42 metabolites, such as saccharides, phenolic acids, flavonoids, amino acids, and fatty acids. Among them, the flavonoid C-glycosides stand out due to their high relative abundance and previous reports on their anticancer bioactivity. For a better understanding of the bioactive mechanisms, four flavonoids (vitexin, kaempferol-3-O-rutinoside, luteolin, and isoorientin) were selected for molecular docking on hallmark protein targets in lung cancer as represented by γ-PI3K, EGFR, and CDK2 through in-silico studies. In these models, kaempferol-3-O-rutinoside and vitexin had the highest binding scores on γ-PI3K and CDK2, followed by isoorientin, so they could be highly responsible for the bioactive properties of C. racemosa extracts.

Detailed metabolite profiling and in vitro studies of Urospermum picroides as a potential functional food.

Wild edible plants (WEP) are part of the Mediterranean culinary culture and can be used as famine foods in times of severe food shortages. Urospermum picroides is a WEP that grows under harsh conditions and represents an opportunity to expand and diversify the global food supply. However, little is known about its chemical profile. In this study, liquid chromatography coupled to HRESIMS allowed the identification of 77 metabolites in U. picroides extract, among which 12 sesquiterpene-amino acid conjugates are reported here for the first time. Due to the novelty of these conjugates, GNPS molecular networking was used to provide information on their fragmentation pathway. Further, the sesquiterpene enriched U. picroides extract showed a moderate anti-inflammatory effect in LPS-stimulated THP1-macrophages by increasing IL-10 secretion while decreasing pro-inflammatory IL-6 secretion at 50 µg/mL. Our study provides evidence for the potential use of U. picroides as an anti-inflammatory functional food and nutraceutical agent.

Bioherbicidal Activity and Metabolic Profiling of Allelopathic Metabolites of Three Cassia species using UPLC-qTOF-MS/MS and Molecular Networking.

INTRODUCTION: Compared to synthetic herbicides, natural products with allelochemical properties can inhibit weed germination, aiding agricultural output with less phytotoxic residue in water and soil. OBJECTIVES: To identify natural product extracts of three Cassia species; C. javanica, C. roxburghii, and C. fistula and to investigate the possible phytotoxic and allelopathic potential. METHODS: Allelopathic activity of three Cassia species extracts was evaluated. To further investigate the active constituents, untergated metabolomics using UPLC-qTOF-MS/MS and ion-identity molecular networking (IIMN) approach was performed to identify and determine the distribution of metabolites in different Cassia species and plant parts. RESULTS: We observed in our study that the plant extracts showed consistent allelopathic activity against seed germination (P < 0.05) and the inhibition of shoot and root development of Chenopodium murale in a dose-dependent manner. Our comprehensive study identified at least 127 compounds comprising flavonoids, coumarins, anthraquinones, phenolic acids, lipids, and fatty acid derivatives. We also report the inhibition of seed germination, shoot growth, and root growth when treated with enriched leaf and flower extracts of C. fistula, and C. javanica, and the leaf extract of C. roxburghii. CONCLUSION: The present study recommends further evaluation of Cassia extracts as a potential source of allelopathic compounds in agricultural systems.

Family Myrtaceae: The treasure hidden in the complex/diverse composition.

Myrtaceae is one of the most important plants families, being regarded as the eighth largest flowering plant family. It includes many genera of utmost ecological and economical importance distributed all over the world. This review aimed to report the latest studies on this family focusing on certain widely used plants including Eucalyptus sp., Eugenia sp. (Eugenia uniflora, Eugenia sulcata), Syzygium sp. (Syzygium aromaticum and Syzygium cumini), Psidium sp., Pimenta dioica, Myrtus sp. (Myrtus communis), Myrciaria sp. and Melaleuca alternifolia. The extraction of bioactive compounds has been evolving through the optimization of conventional methods and the use of emerging technologies. Supercritical CO2 was applied for essential oils and ultrasound for polyphenols leading to extracts and essential oils rich in bioactive compounds. Advances in the field of encapsulation and delivery systems showed promising results in the production of stable essential oils nanoemulsions and liposomes and the production of plant extracts in the form of nanoparticles. Moreover, a significant increase in the number of patents was noticed especially the application of Myrtaceae extracts in the pharrmacuetucal field. The applications of ceratin plants (Pimenta dioica, Melaleuca alternifolia, Syzygium aromaticum essential oils or Myrciaria cauliflora peel extract) in food area (either as a free or encapsulated form) also showed interesting results in limiting microbial spoilage of fresh meat and fish, slowing oxidative degradation in meat products, and inhibiting aflatoxin production in maize. Despite the massive literature on Myrtaceae plants, advances are still necessary to optimize the extraction with environmentally friendly technologies and carry out risk assessment studies should be accomplished to harness the full potential in food, industrial and pharmaceutical applications.

Metabolic profiling of Ochradenus baccatus Delile. utilizing UHPLC-HRESIMS in relation to the in vitro biological investigations.

Ochradenus baccatus Delile (Resedaceae) is a desert plant with edible fruits native to the Middle East. Few investigators have reported antibacterial, antiparasitic and anti-cancer activities of the plant. Herein we evaluated the cytotoxic activity of O. baccatus using four cell lines and a zebrafish embryo model. Additionally, liquid chromatography coupled with mass spectroscopy was performed to characterize the extract's main constituents. The highest cytotoxicity was observed against human cervical adenocarcinoma (HeLa), with CC50 of 39.1 µg/mL and a selectivity index (SI) of 7.23 (p < 0.01). Metabolic analysis of the extract resulted in the annotation of 57 metabolites, including fatty acids, flavonoids, glucosinolates, nitrile glycosides, in addition to organic acids. The extract showed an abundance of hydroxylated fatty acids (16 peaks). Further, 3 nitrile glycosides have been identified for the first time in Ochradenus sp., in addition to 2 glucosinolates. These identified phytochemicals may partially explain the cytotoxic activity of the extract. We propose O. baccatus as a possible safe food source for further utilization to partially contribute to the increasing food demand specially in Saharan countries.

Iphiona mucronata (Forssk.) Asch. & Schweinf. A Comprehensive Phytochemical Study via UPLC-Q-TOF-MS in the Context of the Embryo- and Cytotoxicity Profiles.

Iphiona mucronata (Family Asteraceae) is widely distributed in the Eastern desert of Egypt. It is a promising plant material for phytochemical analysis and pharmacologic studies, and so far, its specific metabolites and biological activity have not yet been thoroughly investigated. Herein, we report on the detailed phytochemical study using UPLC-Q-TOF-MS approach. This analysis allowed the putative annotation of 48 metabolites belonging to various phytochemical classes, including mostly sesquiterpenes, flavonoids, and phenolic acids. Further, zebrafish embryotoxicity has been carried out, where 100 µg/mL extract incubated for 72 h resulted in a slow touch response of the 10 examined larvae, which might be taken as a sign of a disturbed peripheral nervous system. Results of in vitro testing indicate moderate cytotoxicity towards VERO, FaDu, and HeLa cells with CC50 values between 91.6 and 101.7 µg/mL. However, selective antineoplastic activity in RKO cells with CC50 of 54.5 µg/mL was observed. To the best of our knowledge, this is the first comprehensive profile of I. mucronata secondary metabolites that provides chemical-based evidence for its biological effects. A further investigation should be carried out to precisely define the underlying mechanisms of toxicity.

The Potential Neuroprotective Effect of Cyperus esculentus L. Extract in Scopolamine-Induced Cognitive Impairment in Rats: Extensive Biological and Metabolomics Approaches.

The aim of the present study is to investigate the phytochemical composition of tiger nut (TN) (Cyperus esculentus L.) and its neuroprotective potential in scopolamine (Scop)-induced cognitive impairment in rats. The UHPLC-ESI-QTOF-MS analysis enabled the putative annotation of 88 metabolites, such as saccharides, amino acids, organic acids, fatty acids, phenolic compounds and flavonoids. Treatment with TN extract restored Scop-induced learning and memory impairments. In parallel, TN extract succeeded in lowering amyloid beta, ß-secretase protein expression and acetylcholine esterase (AChE) activity in the hippocampus of rats. TN extract decreased malondialdehyde levels, restored antioxidant levels and reduced proinflammatory cytokines as well as the Bax/Bcl2 ratio. Histopathological analysis demonstrated marked neuroprotection in TN-treated groups. In conclusion, the present study reveals that TN extract attenuates Scop-induced memory impairments by diminishing amyloid beta aggregates, as well as its anti-inflammatory, antioxidant, anti-apoptotic and anti-AChE activities.

Anti-androgenic potential of the fruit extracts of certain Egyptian Sabal species and their genetic variability studies: a metabolomic-molecular modeling approach.

This work aimed to evaluate the anti-androgenic activity of S. blackburniana Glazebrook, S. causiarum (O. F. Cook) Becc, and S. palmetto (Walter) Lodd. Ex Schult fruit extracts in rats using Hershberger assay. Furthermore, to annotate secondary metabolites using LC-HRMS technique, to investigate underlying mechanisms responsible for 5-α-reductase inhibitory activity in silico and to compare cytotoxic effects in vitro against human prostatic stromal myofibroblast (WPMY-1) and human benign prostatic hyperplasia (BPH-1) cell lines using MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (spectrophotometrically). The results showed significant anti-androgenic implications with varying degrees, markedly decreased sex organ weights, reduction in testosterone and increase in LH and FSH serum levels. Genetic diversity study ensured the correct genotype and revealed outperformance of SCoT compared with CBDP markers to interpret polymorphism among selected species. S. blackburniana exhibited selective cytotoxic activity against BPH-1 compared to finasteride. Molecular docking of 59 dereplicated metabolites belonging to various chemical classes revealed that helasaoussazine, pinoresinol and tetra-O-caffeoylquinic acid are the top inhibitors of 5-α-reductase-2. Our study provides an insight into the anti-androgenic activity of selected species of Egyptian Sabal supported by docking study for the first time, demonstrates safety toward liver and kidney and highlights a new potential therapeutic candidate for anti-androgenic related disease such as benign prostatic hyperplasia.

The phloroglucinol calcitrinone A, a novel mitochondria-targeting agent, induces cell death in breast cancer cells.

Breast cancer is the most common cancer and the leading cause of cancer-related mortality among females worldwide. From the leaves of Callistemon citrinus, we have isolated a novel phloroglucinol dimer, calcitrinone A, and analyzed its potential anticancer activity using the triple-negative breast cancer cell line MDA-MB-231. Calcitrinone A decreased the total intracellular ATP levels, inhibited proliferation, and induced apoptosis in MDA-MB-231 cells, but was less toxic to peripheral blood mononuclear cells. The antiproliferative and apoptosis-inducing effects of calcitrinone A were confirmed in vivo using breast cancer xenografts grown on chick chorioallantoic membranes. Mechanistic analysis showed mitochondrial membrane-potential dissipation and interference with energy-yielding processes resulting in cell accumulation in the S phase of the cell cycle. Seahorse assay analysis revealed an early inhibition of mitochondrial oxidative phosphorylation (OXPHOS). At the molecular level, calcitrinone A inhibited activity of the succinate-coenzyme Q reductase (SQR) (mitochondrial complex II). In silico docking identified the coenzyme Q binding pocket as a possible high affinity binding site for calcitrinone A in SQR. Inhibition of complex II was accompanied by strong elevation of mitochondrial superoxide and cytoplasmic ROS. Calcitrinone A might be a promising anticancer lead compound acting through the interference with the mitochondrial complex II activity.

The Untargeted Phytochemical Profile of Three Meliaceae Species Related to In Vitro Cytotoxicity and Anti-Virulence Activity against MRSA Isolates.

BACKGROUND: A high mortality rate is associated with about 80% of all infections worldwide, mainly due to antimicrobial resistance. Various antimicrobial and cytotoxic activities have been proposed for Meliaceae species. This study aimed to evaluate the in vitro anti-virulence and cytotoxic effect of the leaf extracts of Aphanamixis polystachya, Toona ciliata and Melia azedarach against five MRSA strains and on three cancer cell lines, followed by biological correlation to their encompassed phytoconstituents. MATERIAL AND METHODS: We explored three plants of this family against a panel of Methicillin-resistant Staphylococcus aureus (MRSA) strains and several cancer cell lines to select the most promising candidates for further in vivo and preclinical studies. The phytochemical composition was evaluated by UHPLC-QTOF-MS untargeted profiling. Cell viability was assessed by SRB assay. Minimum Inhibitory Concentration was carried out by using the agar micro-dilution technique. Inhibition of biofilm formation and preformed biofilm disruption were assessed spectrophotomertically, according to the Sultan and Nabil method (2019). RESULTS: A total of 279 compounds were putatively annotated to include different phytochemical classes, such as flavonoids (108), limonoids/terpenoids (59), phenolic acids (49) and lower-molecular-weight phenolics (39). A. polystachya extract showed the most potent cytotoxic activity against Huh-7, DU-145 and MCF-7 cell lines (IC50 = 3, 3.5 and 13.4 µg mL-1, respectively), followed by M. azedarach, with no effect recorded for T. ciliata extract. Furthermore, both A. polystachya and M. azedarach extracts showed promising anti-virulence and antimicrobial activities, with A. polystachya being particularly active against MRSA. These two latter extracts could inhibit and disrupt the biofilm, formed by MRSA, at sub-lethal concentrations. Interestingly, the extracts inhibited hemolysin-α enzyme, thus protecting rabbit RBCs from lysis. A. polystachya extract reduced the pigmentation and catalase enzyme activity of tested pigmented strains better than M. azedarach at both tested sub-MICs. Consequently, susceptibility of the extract-treated cells to oxidant killing by 200 mM H2O2 increased, leading to faster killing of the cells within 120 min as compared to the extract-non-treated cells, likely due to the lower antioxidant-scavenging activity of cells exhibiting less staphyloxanthin production. CONCLUSION: These findings suggested that both A. polystachya and M. azedarach natural extracts are rich in bioactive compounds, mainly limonoids, phenolics and oxygenated triterpenoids, which can combat MRSA biofilm infections and could be considered as promising sources of therapeutic cytotoxic, antibiofilm and anti-virulence agents.

Cytotoxic potential of three Sabal species grown in Egypt: a metabolomic and docking-based study.

The phytochemical profiles of leaves and pollen grains' extracts of S. causiarum, S. palmetto and S. yapa were investigated and characterised by LC-HR-MS-based metabolomic analysis. Further, biomarker metabolites were determined using multivariate and clustering analysis. S. causiarum leaves extract along with both S. palmetto and S. yapa pollen grains extracts showed interesting in vitro cytotoxic activity using MTT assay against PC-3 cell lines. While, both S. yapa leaves and pollen grains-derived extracts and S. causiarum pollen grains-derived extracts were active against A-172 cell line. OPLS-DA models was generated, to putatively determine the most active cytotoxic metabolites, these models suggested that alkaloids, flavonoids and phenolic acids are the most important metabolites in the active extracts. In silico analysis (neural-networking-based activity prediction and docking studies) of these top-scoring metabolites further supported OPLS-DA models predictability. This study could be considered as primary step in the in-depth exploration of bioactive natural products from Sabal.

Exploring the Antivirulence Activity of Pulverulentone A, a Phloroglucinol-Derivative from Callistemon citrinus Leaf Extract, against Multi-Drug Resistant Pseudomonas aeruginosa.

(1) Background: Bacterial resistance to antibiotics is a global life-threatening issue. Antivirulence therapy is a promising approach to combat bacterial infections as it disarms the bacteria from their virulence factors with reduced selective pressure and a lower chance of resistance. (2) Methods: Callistemon citrinus leaf extract and its major constituent, Pulverulentone A, were tested for their ability to inhibit biofilm, exopolysaccharides, pyocyanin and proteases produced by MDR P. aeruginosa. In addition, a Galleria mellonella larvae model was employed to evaluate the in vivo cytotoxicity of Pulverulentone A and its ability to combat Pseudomonas infection. Docking study was further performed to investigate Pulverulentone A druggability against main quorum sensing (QS) targets expressed by P. aeruginosa; (3) Results: Both C. citrinus extract and the isolated compound could inhibit biofilm formation, extracellular polymeric substances (EPS) and pigment production by the tested isolates. Unexpectedly, no significant inhibition was observed on proteases production. The in silico docking analysis revealed good interactions of Pulverulentone A with all QS targets examined (LasR, MyfR/PqsR, QscR). Pulverulentone A was safe up to 400 µg·mL-1 in Galleria caterpillars. Moreover, pre-treatment of P. aeruginosa with Pulverulentone A slightly enhanced the survival of the infected larvae. (4) Conclusions: The present study proves Pulverulentone A safety with significant in vitro and in silico antivirulence potential against P. aeruginosa.

The UHPLC-QTOF-MS Phenolic Profiling and Activity of Cydonia oblonga Mill. Reveals a Promising Nutraceutical Potential.

Cydonia oblonga Mill., normally known as the quince fruit, has been widely used in agro-food industries mainly to produce jams and jellies. However, other parts of the plants are still underutilized and not completely assessed for their nutraceutical profile. Therefore, in this work, the polyphenolic profile of C. oblonga was investigated using an untargeted metabolomics approach based on high-resolution mass spectrometry. Several compounds were identified in the different parts of the plants, including flavonoids (i.e., anthocyanins, flavones, flavan-3-ols, and flavonols), phenolic acids (both hydroxycinnamics and hydroxybenzoics), low-molecular-weight phenolics (tyrosol equivalents), lignans, and stilbenes. Overall, C. oblonga leaves showed the highest in vitro antioxidant potential, as revealed by 2,2-difenil-1-picrylhydrazyl (DPPH), 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and cupric ion reducing antioxidant capacity (CUPRAC) assays, being 189.5, 285.6, 158.9, and 348.8 mg Trolox Equivalent/g, respectively. The enzymes acetyl- and butyryl-cholinesterases were both inhibited by the different plant parts of C. oblonga, with stems showing the higher inhibitory potential. Interestingly, the fruit extracts were the only parts inhibiting the α-glucosidase, with a value of 1.36 mmol acarbose equivalents (ACAE)/g. On the other hand, strong tyrosinase inhibition was found for stems and leaves, being 72.11 and 68.32 mg Kojic acid Equivalent/g, respectively. Finally, a high number of significant (0.05 < p < 0.01) correlations were outlined between phenolics (mainly anthocyanins, flava-3-ols, and tyrosol equivalents) and the different biological assays. Taken together, our findings suggest a potential exploitation of C. oblonga leaves and stems for the food, pharmaceutical, and cosmetic industries.

Chemometric-enhanced metabolic profiling of five Pinus species using HPLC-MS/MS spectrometry: Correlation to in vitro anti-aging, anti-Alzheimer and antidiabetic activities.

Detailed metabolic profiling of needles of five Pinus species was investigated using complementary HPLC-MS/MS techniques together with supervised and unsupervised chemometric tools. This resulted in putative identification of 44 compounds belonging to flavonoids, phenolics, lignans, diterpenes and fatty acids. Unsupervised principal component analysis showed that differences were maintained across the metabolites characteristic of each Pinus species, are mainly related to di-O-p-coumaroyltrifolin, p-coumaroyl quinic acid derivative, arachidonic acid, hydroxypalmitic acid, isopimaric acid and its derivative. A supervised Partial Least Squares regression analysis was performed to correlate HPLC-MS/MS profiles with the variation observed in the in vitro anticholinesterase, antiaging and anti-diabetic potential. All investigated Pinus extracts exerted their antiaging activity via increasing telomerase and TERT levels in normal human melanocytes cells compared to the control (untreated cells). Profound inhibition activities of acetylcholinesterase and dipeptidyl peptidase-4 were also observed with P. pinea and P. canariensis extracts having comparable antidiabetic activities to sitagliptin as a standard antidiabetic drug. Our findings suggested that pine needles are a good source of phenolics and diterpenoids that have possible health promoting activities in management and alleviation of diabetic conditions and Alzheimer disease.

UHPLC-QTOF-MS based metabolomics and biological activities of different parts of Eriobotrya japonica.

Eriobotrya japonica, commonly known as loquat, has been used traditionally for the treatment of different diseases. Herein, untargeted profiling based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was used to depict the phytochemical profile of loquat roots, leaves, stems, seeds, and fruits. This allowed the tentative annotation of 349 compounds, representing different phytochemical classes that included flavonoids, phenolic acids, lignans, stilbenes, and terpenoids. Among others, low molecular weight phenolics (tyrosol derivatives) and terpenoids were the most abundant phytochemicals. After that, in vitro antioxidant and enzyme inhibition assays were applied to investigate the biological activity of the different organs of Eriobotrya japonica. Roots of E. japonica exhibited the highest antioxidant capacity, showing 181.88, 275.48, 325.18, 169.74 mg Trolox equivalent (TE)/g in DPPH, ABTS, CUPRAC, and FRAP assays, respectively. Furthermore, the root extract of E. japonica strongly inhibited butyryl cholinesterase (3.64 mg galantamine equivalent (GALAE)/g), whereas leaves, stems, seeds, and fruits showed comparable inhibition of both acetyl and butyryl cholinesterases. All the investigated organs of E. japonica exhibited in vitro tyrosinase inhibition (57.27-71.61 mg Kojic Acid Equivalent (KAE)/g). Our findings suggest a potential food and pharmaceutical exploitation of different organs of E. japonica (mainly roots) in terms of enrichment with health-promoting phenolics and triterpenes.

Unravelling the anthelmintic bioactives from Jasminum grandiflorum L. subsp. Floribundum adopting in vitro biological assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Jasminum grandiflorum L. is a medicinal plant widely used in the traditional system of Medicine as an anthelmintic in ringworm infections, for treating ulcers, stomatitis, skin diseases, and wounds. AIM OF THE STUDY: The emergence of resistance by different parasites to currently used chemicals has been reported. There are increasing needs for more effective and safer parasiticides. Therefore, the current study was designed to investigate the methanolic extract of the aerial parts of J. grandiflorum subsp. Floribundum (JGTE) to confirm its traditional uses as anthelmintic through a bioassay-guided fractionation and isolation of the active components with anthelmintic activity. MATERIALS AND METHODS: The JGTE was partitioned into dichloromethane (DCM-F) and n-butanol (BuOH-F) fractions. The JGTE, fractions, and the isolated compounds were tested in vitro for their anthelmintic activity using two nematodes; one larval stage of cestode and one arthropod. Four major compounds were isolated from the most active fraction (BuOH-F) including two flavonoids and two secoirridoid glycosides, identified as kaempferol-3-O-neohesperoside (1), rutin (2), oleuropein (3), and ligstroside (4). RESULTS: Among the isolated compounds from most active fraction (BuOH-F), rutin (2) displayed the highest anthelmintic activity in a dose-dependent activity with IC50 of 41.04 µg/mL against H. muscae adult worm, followed by ligstroside (4) with IC50 of 50.56 µg/mL. CONCLUSIONS: These findings could advocate the traditional use of J. grandiflorum L. and provide further insight into the anthelmintic activity of flavonoids.

Phytochemical profile, enzyme inhibition activity and molecular docking analysis of Feijoa sellowiana O. Berg.

Feijoa sellowiana leaves and fruits have been investigated as a source of diverse bioactive metabolites. Extract and eight metabolites isolated from F. sellowiana leaves were evaluated for their enzymatic inhibitory activity against α-glucosidase, amylase, tyrosinase, acetylcholinestrerase and butyrylcholinesterase both in vitro and in silico. Feijoa leaves' extract showed strong antioxidant activity and variable levels of inhibitions against target enzymes with a strong anti-tyrosinase activity (115.85 mg Kojic acid equivalent/g). Additionally, α-tocopherol emerged as a potent inhibitor of AChE and BChE (5.40 & 10.38 mmol galantamine equivalent/g, respectively). Which was further investigated through molecular docking and found to develop key enzymatic interactions in AChE and BChE active sites. Also, primetin showed good anti BChE (11.70 mmol galantamine equivalent/g) and anti-tyrosinase inhibition (90.06 mmol Kojic acid equivalent/g) which was also investigated by molecular docking studies. Highlights Isolation of eight bioactive constituents from Feijoa sellowiana leaves. In vitro assays using different enzymatic drug targets were investigated. In silico study was performed to define compound interactions with target proteins. Feijoa leaf is an excellent source of anti-AChE and antityrosinase bioactives.

Green-synthesized zinc oxide nanoparticles, anti-Alzheimer potential and the metabolic profiling of Sabal blackburniana grown in Egypt supported by molecular modelling.

Nowadays, the biosynthesis of metal nanoparticles, particularly from plants, has been gaining interest. In the present work, the methanolic extracts of leaves, fruits, and the pollen grains of Sabal blackburniana were used for the green synthesis of ZnO nanoparticles, which were early detected by the formation of precipitate and further confirmed by UV-vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infra-red (FT-IR) spectroscopy and zeta potential (ZP) studies. TEM analysis has shown different shapes, predominantly irregular small spherical narrow particles included in hexagonal structures with size ranging from 2.23 to 49.56 nm. The XRD pattern confirmed that all synthesized ZnO nanoparticles have wurtzite hexagonal structure with crystalline nature. The average particle crystallite sizes were 47.21, 47.67 and 47.8 nm. The UV-visible spectra showed λ max in the range of 354-368 nm, which indicated the presence of ZnO nanoparticles. The FT-IR analysis identifies the characteristic functional groups present on the surface of ZnO nanoparticles. The ZP determination demonstrated that all representative selected synthesized ZnONPs exhibited acceptable ZP values of -30.8 to -45.9 mV, which indicated their good stability. In addition, the anti-Alzheimer potential of the selected extracts and ZnONPs was evaluated by assessing acetylcholinesterase inhibitory activity in vitro according to the improved Ellman method. The results indicated that the selected extracts have acetylcholinesterase inhibitory activity, and highlighted the promising inhibitory potential of green-synthesized ZnONPs using pollen grains, fruits and leaves extracts; they exhibited a potent inhibitory effect with IC50 values 63.78 ± 1.04651, 81.985 ± 3.075 and 117.95 ± 6.858 ng ml-1 respectively in comparison to donepezil as standard (IC50 = 50.7 ± 5.769 ng ml-1). Dereplication analysis of the selected extracts was performed using LC-MS; metabolic profiling revealed the presence of 41 compounds belonging to various chemical classes: flavonoids, steroidal saponins, terpenoids, alkaloids, lignans, sterols and fatty acids. Docking these dereplicated metabolites against the human AChE showed that the non-glycosylated flavonoid class of compounds was able to achieve interesting binding modes inside the AChE active site; they are suggested to be associated with the observed anti-AChE activity of Sabal extracts. This study is the first report to shed light on the acetylcholinesterase inhibitory activity of green-synthesized ZnO nanoparticles of S. blackburniana metabolites.

Metabolome classification via GC/MS and UHPLC/MS of olive fruit varieties grown in Egypt reveal pickling process impact on their composition.

The role of variety and effects of pickling on Egyptian olive fruit metabolome was determined using mass spectrometry-based metabolomics targeting nutrients and bioactive metabolities. The analyzed fresh olive fruit varieties included Manzanilo, Picual, Koroneiki, and Coratina, while the pickled samples included the Manzanilo and Picual varieties. Profiling of primary and secondary metabolites resulted in the detection of 201 metabolites. Variation between varieties was mostly observed among sugars, sugar alcohols, secoiridoids, and flavonoids. An abundance of carbohydrates and O-glycosides in Picual and Manzanilo versus enrichment of secoiridoids in Picual and Coratina olives viz. dehyro-oleuropein could account for the difference in palatability and health benefits among varieties. Herein, 13 new compounds are reported in the tested varieties, of which 10 appeared exclusively in pickled samples. Generally, pickled samples were characterized by the relative abundance of secoiridoids regarded as important markers for the pickling process. Metabolites profiling provided greater insight into the pickling process as a preservation method and accounted for the improved organoleptic characters in pickled fruits.

Pimenta Oil as A Potential Treatment for Acinetobacter Baumannii Wound Infection: In Vitro and In Vivo Bioassays in Relation to Its Chemical Composition.

Bacterial biofilm contributes to antibiotic resistance. Developing antibiofilm agents, more favored from natural origin, is a potential method for treatment of highly virulent multidrug resistant (MDR) bacterial strains; The potential of Pimenta dioica and Pimenta racemosa essential oils (E.Os) antibacterial and antibiofilm activities in relation to their chemical composition, in addition to their ability to treat Acinetobacter baumannii wound infection in mice model were investigated; P. dioica leaf E.O at 0.05 µg·mL-1 efficiently inhibited and eradicated biofilm formed by A. baumannii by 85% and 34%, respectively. Both P. diocia and P. racemosa leaf E.Os showed a bactericidal action against A. baumanii within 6h at 2.08 µg·mL-1. In addition, a significant reduction of A. baumannii microbial load in mice wound infection model was found. Furthermore, gas chromatography mass spectrometry analysis revealed qualitative and quantitative differences among P. racemosa and P. dioica leaf and berry E.Os. Monoterpene hydrocarbons, oxygenated monoterpenes, and phenolics were the major detected classes. ß-Myrcene, limonene, 1,8-cineole, and eugenol were the most abundant volatiles. While, sesquiterpenes were found as minor components in Pimenta berries E.O; Our finding suggests the potential antimicrobial activity of Pimenta leaf E.O against MDR A. baumannii wound infections and their underlying mechanism and to be further tested clinically as treatment for MDR A. baumannii infections.