Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation to Elucidate the Molecular Targets and Potential Mechanism of Phoenix dactylifera (Ajwa Dates) against Candidiasis.

Candidiasis, caused by opportunistic fungal pathogens of the Candida genus, poses a significant threat to immunocompromised individuals. Natural compounds derived from medicinal plants have gained attention as potential sources of anti-fungal agents. Ajwa dates (Phoenix dactylifera L.) have been recognized for their diverse phytochemical composition and therapeutic potential. In this study, we employed a multi-faceted approach to explore the anti-candidiasis potential of Ajwa dates' phytochemicals. Utilizing network pharmacology, we constructed an interaction network to elucidate the intricate relationships between Ajwa dates phytoconstituents and the Candida-associated molecular targets of humans. Our analysis revealed key nodes in the network (STAT3, IL-2, PTPRC, STAT1, CASP1, ALB, TP53, TLR4, TNF and PPARG), suggesting the potential modulation of several crucial processes (the regulation of the response to a cytokine stimulus, regulation of the inflammatory response, positive regulation of cytokine production, cellular response to external stimulus, etc.) and fungal pathways (Th17 cell differentiation, the Toll-like receptor signaling pathway, the C-type lectin receptor signaling pathway and necroptosis). To validate these findings, molecular docking studies were conducted, revealing the binding affinities of the phytochemicals towards selected Candida protein targets of humans (ALB-rutin (-9.7 kJ/mol), STAT1-rutin (-9.2 kJ/mol), STAT3-isoquercetin (-8.7 kJ/mol), IL2-ß-carotene (-8.5 kJ/mol), CASP1-ß-carotene (-8.2 kJ/mol), TP53-isoquercetin (-8.8 kJ/mol), PPARG-luteolin (-8.3 kJ/mol), TNF-ßcarotene (-7.7 kJ/mol), TLR4-rutin (-7.4 kJ/mol) and PTPRC-rutin (-7.0 kJ/mol)). Furthermore, molecular dynamics simulations of rutin-ALB and rutin-STAT1 complex were performed to gain insights into the stability and dynamics of the identified ligand-target complexes over time. Overall, the results not only contribute to the understanding of the molecular interactions underlying the anti-fungal potential of specific phytochemicals of Ajwa dates in humans but also provide a rational basis for the development of novel therapeutic strategies against candidiasis in humans. This study underscores the significance of network pharmacology, molecular docking and dynamics simulations in accelerating the discovery of natural products as effective anti-fungal agents. However, further experimental validation of the identified compounds is warranted to translate these findings into practical therapeutic applications.

Saponin-Derived Silver Nanoparticles from Phoenix dactylifera (Ajwa Dates) Exhibit Broad-Spectrum Bioactivities Combating Bacterial Infections.

The emergence of antibiotic resistance poses a serious threat to humankind, emphasizing the need for alternative antimicrobial agents. This study focuses on investigating the antibacterial, antibiofilm, and anti-quorum-sensing (anti-QS) activities of saponin-derived silver nanoparticles (AgNPs-S) obtained from Ajwa dates (Phoenix dactylifera L.). The design and synthesis of these novel nanoparticles were explored in the context of developing alternative strategies to combat bacterial infections. The Ajwa date saponin extract was used as a reducing and stabilizing agent to synthesize AgNPs-S, which was characterized using various analytical techniques, including UV-Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). The biosynthesized AgNPs-S exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria due to their capability to disrupt bacterial cell membranes and the leakage of nucleic acid and protein contents. The AgNPs-S effectively inhibited biofilm formation and quorum-sensing (QS) activity by interfering with QS signaling molecules, which play a pivotal role in bacterial virulence and pathogenicity. Furthermore, the AgNPs-S demonstrated significant antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and cytotoxicity against small lung cancer cells (A549 cells). Overall, the findings of the present study provide valuable insights into the potential use of these nanoparticles as alternative therapeutic agents for the design and development of novel antibiotics. Further investigations are warranted to elucidate the possible mechanism involved and safety concerns when it is used in vivo, paving the way for future therapeutic applications in combating bacterial infections and overcoming antibiotic resistance.

Phytochemical Analysis, Antioxidant, and Antimicrobial Activities of Ducrosia flabellifolia: A Combined Experimental and Computational Approaches.

Ducrosia flabellifolia Boiss. is a rare desert plant known to be a promising source of bioactive compounds. In this paper, we report for the first time the phytochemical composition and biological activities of D. flabellifolia hydroalcoholic extract by using liquid chromatography-electrospray tandem mass spectrometry (ESI-MS/MS) technique. The results obtained showed the richness of the tested extract in phenols, tannins, and flavonoids. Twenty-three phytoconstituents were identified, represented mainly by chlorogenic acid, followed by ferulic acid, caffeic acid, and sinapic acid. The tested hydroalcoholic extract was able to inhibit the growth of all tested bacteria and yeast on agar Petri dishes at 3 mg/disc with mean growth inhibition zone ranging from 8.00 ± 0.00 mm for Enterococcus cloacae (E. cloacae) to 36.33 ± 0.58 mm for Staphylococcus epidermidis. Minimal inhibitory concentration ranged from 12.5 mg/mL to 200 mg/mL and the hydroalcoholic extract from D. flabellifolia exhibited a bacteriostatic and fungistatic character. In addition, D. flabellifolia hydroalcoholic extract possessed a good ability to scavenge different free radicals as compared to standard molecules. Molecular docking studies on the identified phyto-compounds in bacterial, fungal, and human peroxiredoxin 5 receptors were performed to corroborate the in vitro results, which revealed good binding profiles on the examined protein targets. A standard atomistic 100 ns dynamic simulation investigation was used to further evaluate the interaction stability of the promising phytocompounds, and the results showed conformational stability in the binding cavity. The obtained results highlighted the medicinal use of D. flabellifolia as source of bioactive compounds, as antioxidant, antibacterial, and antifungal agent.

In silico analysis of the interactions of certain flavonoids with the receptor-binding domain of 2019 novel coronavirus and cellular proteases and their pharmacokinetic properties.

Coronavirus Disease 2019 (COVID-19) has infected more than thirty five million people worldwide and caused nearly 1 million deaths as of October 2020. The microorganism causing COVID-19 was named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV). The aim of this study was to investigate the interactions of twenty-three phytochemicals belonging to different flavonoid subgroups with the receptor binding domain (RBD) of the spike glycoprotein of 2019-nCoV, and cellular proteases [transmembrane serine protease 2 (TMPRSS2), cathepsin B and L (CatB/L)]. The compounds interacted more strongly with CatB and CatL than with the other proteins. Van der Waals and hydrogen bonds played an important role in the receptor-ligand interactions. As a result of RBCI (relative binding capacity index) analysis conducted to rank flavonoids in terms of their interactions with the target proteins, (-)-epicatechin gallate interacted strongly with all the proteins studied. The results obtained from molecular dynamics and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) methods also supported this data. According to Lipinski's rule of five, (-)-epicatechin gallate showed drug-likeness properties. Although this molecule is not capable of crossing the blood-brain barrier (BBB), it was concluded that (-)-epicatechin gallate can be evaluated as a candidate molecule in drug development studies against 2019-nCoV since it was not the substrate of P-gp (P-glycoprotein), did not inhibit any of the cytochrome Ps, and did not show AMES toxicity or hepatotoxicity on eukaryotic cells.

Understanding the molecular interaction of SARS-CoV-2 spike mutants with ACE2 (angiotensin converting enzyme 2).

Covid-19 is a viral disease caused by the virus SARS-CoV-2 that spread worldwide and caused more than 4.3 million deaths. Moreover, SARS-CoV-2 still continues to evolve, and specifically the E484K, N501Y, and South Africa triple (K417N + E484K + N501Y) spike protein mutants remain as the 'escape' phenotypes. The aim of this study was to compare the interaction between the receptor binding domain (RBD) of the E484K, N501Y and South Africa triple spike variants and ACE2 with the interaction between wild-type spike RBD-ACE2 and to show whether the obtained binding affinities and conformations corraborate clinical findings. The structures of the RBDs of the E484K, N501Y and South Africa triple variants were generated with DS Studio v16 and energetically minimized using the CHARMM22 force field. Protein-protein dockings were performed in the HADDOCK server and the obtained wild-type and mutant spike-ACE2 complexes were submitted to 200-ns molecular dynamics simulations with subsequent free energy calculations using GROMACS. Based on docking binding affinities and free energy calculations the E484K, N501Y and triple mutant variants were found to interact stronger with the ACE2 than the wild-type spike. Interestingly, molecular dynamics and MM-PBSA results showed that E484K and spike triple mutant complexes were more stable than the N501Y one. Moreover, the E484K and South Africa triple mutants triggered greater conformational changes in the spike glycoprotein than N501Y. The E484K variant alone, or the combination of K417N + E484K + N501Y mutations induce significant conformational transitions in the spike glycoprotein, while increasing the spike-ACE2 binding affinity.Communicated by Ramaswamy H. Sarma.

Determination of the interaction between the receptor binding domain of 2019-nCoV spike protein, TMPRSS2, cathepsin B and cathepsin L, and glycosidic and aglycon forms of some flavonols.

The novel coronavirus (COVID-19, SARS-CoV-2) is a rapidly spreading disease with a high mortality. In this research, the interactions between specific flavonols and the 2019-nCoV receptor binding domain (RBD), transmembrane protease, serine 2 (TMPRSS2), and cathepsins (CatB and CatL) were analyzed. According to the relative binding capacity index (RBCI) calculated based on the free energy of binding and calculated inhibition constants, it was determined that robinin (ROB) and gossypetin (GOS) were the most effective flavonols on all targets. While the binding free energy of ROB with the spike glycoprotein RBD, TMPRSS2, CatB, and CatL were -5.02, -7.57, -10.10, and -6.11 kcal/mol, the values for GOS were -4.67, -5.24, -8.31, and -6.76, respectively. Furthermore, both compounds maintained their stability for at least 170 ns on respective targets in molecular dynamics simulations. The molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations also corroborated these data. Considering Lipinski's rule of five, ROB and GOS exhibited 3 (MW>500, N or O>10, NH or OH>5), and 1 (NH or OH>5) violations, respectively. Neither ROB nor GOS showed AMES toxicity or hepatotoxicity. The LD50 of these compounds in rats were 2.482 and 2.527 mol/kg, respectively. Therefore, we conclude that these compounds could be considered as alternative therapeutic agents in the treatment of COVID-19. However, the possible inhibitory effects of these compounds on cytochromes (CYPs) should be verified by in vitro or in vivo tests and their adverse effects on cellular energy metabolism should be minimized by performing molecular modifications if necessary.

Element concentration, daily intake of elements, and health risk indices of wild mushrooms collected from Belgrad Forest and Ilgaz Mountain National Park (Turkey).

The aim of this study was to determine the element content of wild edible and inedible mushroom species (Agaricus campestris, Armillaria ostoyae, Boletus reticulatus, Bondarzewia mesenterica, Bovistella utriformis, Cantharellus cibarius, Marasmius oreades, Megacollybia platyphylla, Meripilus giganteus, Neoboletus erythropus, Panellus stipticus, Phaeotremella foliacea, Pleurotus ostreatus, Podoscypha multizonata, Russula aurea, R. chloroides, R. virescens, T. versicolor, Trametes gibbose, and Trichaptum biforme) collected from the Belgrad Forests and the Ilgaz Mountain National Park. Based on the results of elemental analyses, daily metal intake (DMI) and health risk index (HRI) values of edible mushrooms collected from both localities were also calculated. As, Cd, Cr, Se, P, Hg, Cu, Mn, Fe, Zn, Al, Ca, Mg, and K contents of mushrooms were in the ranges of 0.16-3.45, 0.09-2.4, 0.15-2.34, 0.3-8.13, 0.28-11.44, 14.03-37.81, 3.87-108.57, 6.18-149.77, 11.9-776.1, 5.4-317.4, 7.4-355.2, 15.4-3517.3, 266.0-2500.0, and 628.0-24083.0 mg/kg dry weight, respectively. As a result of the DMI and HRI analyses, Cu concentration of B. utriformis (DMI: 46.53 µg/kg body weight/serving, HRI: 1.16) and Cd concentrations of A. campestris (DMI: 0.49 µg/kg body weight/serving, HRI: 1.36), A. ostoyae (DMI: 1.03 µg/kg body weight/serving, HRI: 2.86), B. utriformis (DMI: 0.52 µg/kg body weight/serving, HRI: 1.44), and P. ostreatus (DMI: 0.45 µg/kg body weight/serving, HRI: 1.24) were found to exceed the legal limits determined by authorities. It was concluded that the species collected from the regions in question should be consumed in a controlled manner.

Metal concentrations of wild mushroom species collected from Belgrad forest (Istanbul, Turkey) with their health risk assessments.

Wild edible mushrooms are very popular for both their flavors and nutritional values. However, some mushroom species can be harmful to human health as they accumulate some elements in excessive amounts. The aim of this study was to determine the concentrations of Al, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, P, Se, and Zn of some wild edible (Agaricus arvensis, A. bitorquis, A. sylvaticus, Amanita vaginata, Armillaria mellea, Clavariadelphus pistillaris, Clitocybe nebularis, Clitopilus prunulus, Hygrophorus marzuolus, H. russula, Lactarius volemus, Lycoperdon molle, and Macrolepiota mastoidea) and non-edible mushroom species (A. citrina, Auricularia mesenterica, Chanterellus melanoxeros, Chondrostereum purpureum, Clathrus ruber, L. controversus, L. helvus, and L. zonarius) collected from Belgrad forest (Istanbul, Turkey). Daily intakes of element (DIE) and health risk index (HRI) values of the edible mushroom species were also calculated. The concentrations of the elements in question were determined to be in the ranges of 9.7-556.8, 2.5-2226.7, 0.06-2.52, 0.03-13.17, 3.74-100.19, 13.3-507.4, 2635.0-28614.0, 493.0-2412.0, 6.97-3150.73, 0.29-13.26, 0.38-3.67, and 9.1-293.8 mg/kg, respectively. The Cd concentration of H. russula (DIE: 1.08, HRI: 1.08), Cr concentration of C. nebularis (DIE: 5.64, HRI: 1.88), and the Cu concentration of M. mastoidea (DIE: 42.94, HRI: 1.07) were above the reference values. The results showed that the long-term consumption of H. russula, C. nebularis, and M. mastoidea collected from Belgrad forest can have a negative impact on human health. Therefore, it was concluded that the element concentrations of edible wild mushrooms in this region should be examined periodically.

Campanula macrostachya: biological activity and identification of phenolics using a liquid chromatography electrospray ionization tandem mass spectrometry system.

It is known that some Campanula species are traditionally used because of their anti-allergic, spasmolytic, antiphlogistic, antioxidant, and antiviral properties. This study was designed to evaluate the phytochemical composition, antioxidant, α-amylase, and tyrosinase inhibitory activity of ethyl acetate, methanol, and water extracts of Campanula macrostachya Waldst. & Kit. ex Willd. Chemical compositions were analyzed by spectrophotometric and chromatographic methods. Antioxidant activities of the samples were tested by using five different test systems. Enzyme inhibitory activities of the extracts were also studied. As a result of the LC-ESI-MS/MS analyses, chlorogenic acid, hesperidin, and hyperoside were found to be the major compounds of the extracts, especially the MeOH extract (6559.59, 2499.22, and 2047.66 µg/g extract, respectively). Antioxidant activity tests have proven that MeOH extract showed higher activity than others (DPPH: 4.15 mg/mL, ABTS: 2.05 mg/mL, CUPRAC: 1.80 mg/mL, FRAP: 0.83 mg/mL, phosphomolybdenum: 1.69 mg/mL). Ferrous ion chelating activity of the water extract was 1.03 mg/mL. In α-amylase and tyrosinase inhibitory assays, EtOAc (IC50: 2.54 mg/mL) and MeOH (IC50: 1.51 mg/mL) extracts showed higher activity than the others did. In phosphomolybdenum, CUPRAC, FRAP, and tyrosinase inhibitory assays, the activity was strongly correlated with flavonoids, chlorogenic acid, hesperidin, and hyperoside. On the other hand, phenolic compounds have been found to contribute more to radical scavenging activity. Pearson correlation analysis showed that phenolics and flavonoids were not responsible for the α-amylase inhibitory activity of EtOAc extract.

Evaluation of the metal concentrations of wild mushroom species with their health risk assessments.

The ability of mushrooms to accumulate heavy metals has increased concerns over their toxic effects on human health in recent years. The aim of this study was to determine the metal contents (Zn, Fe, Co, Mn, Cu, Pb, Ni, and Cd), daily intake of metal (DIM) and health risk index (HRI) values of nineteen different mushroom species (edible, inedible, and poisonous) collected from Uzungol, Trabzon (Turkey). Although the area where mushrooms were collected has the status of "Natural Park," there has been an excessive human settlement in recent years. Elemental analyses have shown that Fe, Mn, Cu, Zn, Co, Cd, Pb, and Ni concentrations in mushrooms were in the following ranges: 49.0-1713.0, 3.0-425.0, 3.0-154.0, 16.0-134.0, 0.17-1.79, 0.28-7.88, 0.07-5.68, and 0.24-6.82 mg/kg dry weight, respectively. As a result of DIM analysis, while it was determined that the daily consumption of Hygrophorus pudorinus, Meripilus giganteus, and Sarcodon imbricatus was safe for all the metals examined, HRI analysis showed that only M. giganteus and S. imbricatus can be consumed safely. The content of Cd was found to be above the legal limits determined by the competent authorities. According to Pearson correlation analysis, the correlations between Fe-Pb, Cu-Zn, Cd-Co, Pb-Co, Cd-Fe, Co-Fe, Cd-Pb, and Fe-Mn pairs were statistically significant (p < 0.01). Although the data obtained from this study did not provide clear data on environmental pollution in the area where the samples were collected, it was concluded that the competent authorities should take measures regarding possible environmental pollution at this location.

Metal concentration and health risk assessment of eight Russula mushrooms collected from Kizilcahamam-Ankara, Turkey.

The aim of this study was to determine the essential element (Zn, Ca, K, Fe, Na, and Mg), essential trace element (Co, Mn, Cr, and Cu), and non-essential element (Pb, Ni, and Cd) contents of eight different Russula species (R. risigallina (Batsch) Sacc., R. cyanoxantha (Schaeff.) Fr., R. delica Fr., R. vinosa Lindblad, R. olivacea (Schaeff.) Fr., R. velenovskyi Melzer & Zvára, R. turci Bres., and R. parazurea Jul. Schäff.) collected from Soguksu National Park (Turkey), which is a region away from the city center (Kizilcahamam, Ankara). In addition to the metal contents of these species, daily intake and health risk index values of the metals in question were also calculated and discussed. As a result of elemental analysis, the major elements were K (28980-58,380 mg/kg), Mg (704-1404 mg/kg), and Ca (190-1662 mg/kg). Except for R. risigallina, R. olivacea, and R. velenovskyi, elemental concentrations were within the limits that can be safely consumed as nutrients in terms of their metal content. The daily intakes of metal (DIM) values of R. risigallina and R. olivacea for Cr exceed the reference dose limits (3.80 and 3.87 µg/kg body weight/serving, respectively). According to the health risk index (HRI) measurements, the HRI values of R. risigallina and R. olivacea for Cr and of R. velenovskyi for Cd were found to be above 1.0 and could pose a health risk. In order to analyze the mineral composition variability of the studied mushroom species, principal component analysis (PCA) and the hierarchical cluster analysis (HCA) techniques were also performed. Regarding the significant correlations between all descriptors (r > 0.7), there was a positive relationship between Mg-K, Ni-Co, Ni-Na, Cr-Ni, Cr-Co, Zn-Mg, Zn-K, Cd-Mg couples.

Interaction of certain monoterpenoid hydrocarbons with the receptor binding domain of 2019 novel coronavirus (2019-nCoV), transmembrane serine protease 2 (TMPRSS2), cathepsin B, and cathepsin L (CatB/L) and their pharmacokinetic properties.

As of June 2020, the coronavirus disease 19 (COVID-19) caused by the 2019 new type coronavirus (2019-nCoV) infected more than 7,000,000 people worldwide and caused the death of more than 400,000 people. The aim of this study was to investigate the molecular interactions between monoterpenoids and spike protein of 2019-nCoV together with the cellular proteases [transmembrane serine protease 2 (TMPRSS2), cathepsin B (CatB), and cathepsin L (CatL)]. As a result of the relative binding capacity index (RBCI) analysis, carvone was found to be the most effective molecule against all targets when binding energy and predicted (theoretical) IC50 data were evaluated together. It was found to exhibit drug-likeness property according to the Lipinski's rule-of-five. Carvone has also been determined to be able to cross the blood-brain barrier (BBB) effectively, not a substrate for P-glycoprotein (P-gp), not to inhibit any of the cytochrome P molecules, and to have no toxic effects even on liver cells. In addition, the LD50 dose of carvone in rats was 1.707 mol/kg. Due to its interaction profile with target proteins and excellent pharmacokinetic properties, it has been concluded that carvone can be considered as an alternative agent in drug development studies against 2019-nCoV.

Metal concentration and health risk assessment of fifteen wild mushrooms collected from the Ankara University Campus (Turkey).

The aim of this study is to analyze Fe, Mn, Cu, Zn, Co, Cd, Pb, and Ni contents of Cyclocybe cylindracea, Armillaria mellea, Bjerkandera adusta, Rheubarbariboletus armeniacus, Coprinellus disseminatus, C. micaceus, C. comatus, Inonotus hispidus, Lepista nuda, Leucoagaricus leucothites, Pleurotus ostreatus, Cerioporus squamosus, Schizophyllum commune, Scleroderma verrucosum, and Trametes trogii collected from the Ankara University Besevler 10th Year Campus (Turkey), an area where human settlement and traffic are intense. In addition to the elemental analysis, the daily intake of metal (DIM) and health risk index (HRI) values of the edible ones were also calculated. Fe, Mn, Cu, Zn, Co, Cd, Pb, and Ni concentrations of the samples were found to be 112.0-5079.0, 3.0-124.0, 4.0-77.0, 2.0-196.0, 0.18-2.98, 0.18-5.3, 0.04-10.98, and 0.22-8.23 mg/kg dry weight, respectively. As a result of DIM and HRI analysis, C. cylindracea, L. nuda, and C. squamosus were found to be within the reference dose limits determined by competent authorities and can be safely consumed in terms of all metals studied. However, the Cd, Co, and Fe contents of C. micaceus were found to be above 1.0 (1.06, 4.25, and 7.06, respectively). In addition, it has been found that A. mellea, R. armeniacus, C. comatus, L. leucothites, and P. ostreatus are toxic in terms of Cd/Co, Fe/Pb, Co/Fe, Cd, and Fe contents, respectively. As the area in question is a traffic intensive area, it has been concluded that the emissions of the vehicles should be controlled in terms of legal limits and that the consumption of some mushrooms in this region should not be preferred until necessary measures are taken.

Metal concentration and health risk assessment of wild mushrooms collected from the Black Sea region of Turkey.

Mushrooms are rich sources of organic nutrients (especially proteins). However, they can excessively accumulate metals in their fruiting bodies that pose a risk to human health. The aim of this study was the determination of Cd, Co, Cu, Fe, Mn, Ni, Pb, and Zn contents, daily intake, and health risk index values of some mushroom species collected from the eastern Black Sea region of Turkey (Arsin, Trabzon). The samples were collected from hazelnut gardens that are free from industrial pollution and have a low population density. As a result of elemental analysis, it was determined that the concentration ranges of Cd, Co, Cu, Fe, Mn, Ni, Pb, and Zn in the mushrooms were as follows: 0.29-9.11, 0.04-3.70, 0.01-8.29, 0.18-20.82, 3.1-79.8, 5.2-673.0, 14.9-752.0, 63.0-7769.0 mg/kg dry weight. Daily intakes of all the elements were found to be below the reference dose in Fistulina hepatica, Hydnum repandum, Macrolepiota procera, and Tapinella atrotomentosa. Amanita caesarea, Agrocybe praecox, Amanita vaginata, Cantharellus cibarius, Craterellus cornucopioides, Daedalea quercina, Gymnopus dryophilus, Ganoderma lucidum, and Infundibulicybe gibba were found to have high risk index values especially with respect to Cd, Co, and Pb. According to Pearson correlation analysis, the correlations between Fe-Mn (0.840, p < 0.01) and Pb-Ni (0.7540, p < 0.01) couples are significant.

Enzyme and Biological Activities of the Water Extracts from the Plants Aesculus hippocastanum, Olea europaea and Hypericum perforatum That Are Used as Folk Remedies in Turkey.

Phenolic compounds are secondary metabolites that are found ubiquitously in plants, fruits, and vegetables. Many studies have shown that regular consumption of these compounds could have a positive effect on our health. The aim of this study was to compare the phytochemical contents of the water extracts from three different plants used as folk remedies in Turkey: Aesculus hippocastanum, Olea europaea, and Hypericum perforatum. A liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) analysis was performed to explore the phenolic profiles. The biological activities of these extracts were also evaluated in terms of their antioxidant activities (2,2-diphenyl-1-picrylhydrazyl DPPH, 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid ABTS, Ferric Reducing Antioxidant Power Assay FRAP, cupric ion reducing antioxidant capacity CUPRAC, ß-carotene, phosphomolybdenum, and metal chelating) and enzyme inhibitory properties (against acetylcholinesterase, butyrylcholinesterase, and tyrosinase). The aqueous extract of H. perforatum showed the highest levels of total phenolic, flavonoid, and saponin contents. Protocatechuic acid, vanillic acid, verbascoside, hesperidin, hyperoside, apigenin 7-hexosides, and quercetin were the most common compounds found in this species. The results confirm that A. hippocastanum, O. europaea, and H. perforatum represent a potential source of natural-derived molecules with positive properties that could be used as valid starting point for new food supplements, and drugs in the pharmaceutical, cosmetic, and food industries.

Inhibitory effect of Zataria multiflora Boiss. essential oil, alone and in combination with monolaurin, on Listeria monocytogenes.

Listeria monocytogenes is one of the major causes of infections in developing countries. In this study, chemical composition and anti-listerial effect of the essential oil of Zataria multiflora Boiss. alone and in combination with monolaurin were evaluated at different pH values (5, 6, and 7) and temperatures (5 ˚C and 30 ˚C). Chemical composition of Zataria multiflora Boiss. essential oil was evaluated by gas chromatography-mass spectrometry (GC-MS) analysis. Minimum inhibitory concentration (MIC) of the essential oil and monolaurin were determined using microbroth dilution method and the interactions of essential oil and monolaurin were determined by the evaluation of fractional inhibitory concentrations (FIC) index. Carvacrol (63.20%) and thymol (15.10%) were found as the main components of the essential oil. The MIC values of the oil and monolaurin at pH 7 and 30 ˚C were measured as 312.50 µg mL(-1) and 125.00 µg mL(-1), respectively. Combination of monolaurin and Z. multiflora essential oil were found to act synergistically (FIC index < 0.5) against L. monocytogenes under different pH and temperature conditions. Decrease in the pH and temperature values have increased the anti-listerial activity of monolaurin and the essential oil. The lowest MIC value of monolaurin and essential oil was observed at pH 5 and 5 ˚C. According to our results, the oil alone or in combination with monolaurin at low pH and temperature conditions showed a promising inhibitory effect on L. monocytogenes.

Medicinal Uses, Phytochemistry, and Pharmacology of Origanum onites (L.): A Review.

Origanum onites L., known as Turkish oregano, has great traditional, medicinal, preservative, and commercial importance. It is used for the treatment of several kinds of ailments, such as gastrointestinal disorders, diabetes, high cholesterol, leukemia, bronchitis, etc. In this review, traditional use, phytochemistry, and pharmacology of O. onites reported between 1988 and 2014 were discussed. This review was prepared based on literature survey on scientific journals and books from libraries and electronic sources, such as Web of Science, PubMed, Scopus, Google Scholar, etc. All databases were searched up to June 2014. Several different classes of terpenoids, triterpene acids, phenolic acids, hydroquinones, flavonoids, hydrocarbons, sterols, pigments, fatty acids, tocopherols, and inorganic compounds were detected mainly in the aerial parts of this plant. Pharmacological studies revealed that extracts obtained from several solvents and individual compounds exhibited antimicrobial, antiviral, antioxidant, insecticidal, anticancer, hepatoprotective, genotoxic, antidiabetic, cholinesterase inhibitory, anti-inflammatory, analgesic activities, etc. O. onites, in general, exhibited remarkable activity potential in almost all test systems. The results of toxicity studies indicated that O. onites did not show any significant toxicity and mutagenicity on Drosophila and Salmonella. Toxicity of the extracts/essential oils and also individual compounds should be evaluated on mammalian cells to ensure their safety. The bioactivity of individual compounds aside from terpenoids should also be assessed in detail. Additionally, mode of action for the bioactive compounds should be evaluated to understand the complex pharmacological effects of these phytochemicals.

Chemical composition, antioxidant, and enzyme inhibitory activities of the essential oils of three Phlomis species as well as their fatty acid compositions.

This study aimed to investigate the chemical composition, antioxidant, and enzyme inhibitory activities of the essential oils of Phlomis armeniaca WILLD., P. nissolii L., and P. pungens WILLD. var. pungens as well as their fatty acid contents. Germacrene D was found as the major compound in the oils (24.7, 15.1, and 7.2%, respectively). Additionally, n-hexadecanoic acid, hexahydrofarnesyl acetone, ß-caryophyllene, and linalool were the other main compounds in the oils. Among the fatty acids, C18:3 ω3 and C18:2 ω6 were determined in high quantities in P. armeniaca (23.14 and 18.01%, respectively) and P. pungens var. pungens (24.64 and 17.51%, respectively). The essential oils of P. armeniaca and P. pungens var. pungens showed remarkable antioxidant and metal chelating activities as well as great reducing power potentials. These oils also showed a moderate scavenging effect on ABTS radicals. The oils also exhibited various degrees of inhibitory activities on AChE, BChE, α-amylase, α-glucosidase, and tyrosinase.

Phenolic composition, enzyme inhibitory, and antioxidant activity of Bituminaria bituminosa.

This study aimed to evaluate the in vitro antioxidant and enzyme inhibitory activities of ethyl acetate, methanol, and water extracts of Bituminaria bituminosa. In phosphomolybdenum assay, the methanol extract showed the highest activity (166.78 µmol TEs/g dry plant). The water extract exhibited the highest scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH∙) and 2,2-azino-bis (3-ethylbenzothiazloine-6-sulphonic acid) (ABTS∙+). In addition, it exhibited the highest activity in cupric ion reducing (CUPRAC) and ferric reducing antioxidant power (FRAP) assays (41.26 and 46.82 µmol TEs/g dry plant). The extracts did not show cholinesterase and tyrosinase inhibitory activity. However, α-glucosidase inhibition assay resulted in the superiority of water extract (1233.86 µmol ACEs/g dry plant). In the case of α-amylase inhibitory assay, the ethyl acetate extract showed the highest activity (53.65 µmol ACEs/g dry plant). The water extract exhibited the highest phenolic content (31.70 µmol GAEs/g dry plant). In contrast, the methanol extract was found rich in flavonoid compounds (5.29 µmol REs/g dry plant). The water extract contained considerable amounts of rosmarinic acid, luteolin, quercetin, and rutin. Therefore, it can be used as a source of new and alternative antioxidant and enzyme inhibitory agents.

Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of D-galactose-induced aging mice.

CONTEXT: Morus nigra L. (Moraceae) has various uses in traditional medicine. However, the effect of M. nigra on cognitive impairment has not been investigated yet. OBJECTIVE: The objective of this study is to determine the phenolic acid content and DNA damage protection potential of M. nigra leaf extract and to investigate the extract effect on cognitive impairment and oxidative stress in aging mice. MATERIALS AND METHODS: Phenolic acid content was determined by quantitative chromatographic analysis. DNA damage protection potential was evaluated on pBR322 plasmid DNA. Thirty-two Balb-C mice were randomly divided into four groups (control, d-galactose, d-galactose + M. nigra 50, and d-galactose + M. nigra 100). Mice were administered d-galactose (100 mg/kg, subcutaneous) and M. nigra (50 or 100 mg/kg, orally) daily for 8 weeks. Behavioral responses were evaluated with Morris water maze. Activities of antioxidant enzymes and levels of malondialdehyde (MDA) were assayed in serum, brain, and liver. RESULTS: In extract, vanillic (632.093 µg/g) and chlorogenic acids (555.0 µg/g) were determined. The extract between 0.02 and 0.05 mg/mL effectively protected all DNA bands against the hazardous effect of UV and H2O2. Morus nigra significantly improved learning dysfunctions (p < 0.01), increased memory retention (p < 0.01), reduced MDA levels (p < 0.05), and elevated SOD, GPx, and CAT activities (p < 0.05) compared with the d-galactose group. DISCUSSION AND CONCLUSION: These results show that M. nigra has the potential in improving cognitive deficits in mice and that M. nigra may be useful to suppress aging, partially due to its scavenging activity of free radicals and high antioxidant capacity.