Phenolic Compound Profiles, Cytotoxic, Antioxidant, Antimicrobial Potentials and Molecular Docking Studies of Astragalus gymnolobus Methanolic Extracts.

Since Astragalus is a genus with many important medicinal plant species, the present work aimed to investigate the phytochemical composition and some biological activities of Astragalus gymnolobus. The methanolic fractions of four organs (stems, flowers, leaves, root and whole plant) were quantified and identified by Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (LC-ESI-MS/MS) analysis. Hesperidin, hyperoside, p-hydroxybenzoic acid, protocatechuic acid and p-coumaric acid were identified as main compounds among the extracts. Among all cells, leaf methanol (Lm) extract had the highest cytotoxic effect on HeLa cells (IC50 = 0.069 µg/mL). Hesperidin, the most abundant compound in A. gymnolobus extract, was found to show a strong negative correlation with the cytotoxic effect observed in HeLa cells according to Pearson correlation test results and to have the best binding affinity to targeted proteins by docking studies. The antimicrobial activity results indicated that the most susceptible bacterium against all extracts was identified as Streptococcus pyogenes with 9-11 mm inhibition zone and 8192 mg/mL MIC value. As a result of the research, it was suggested that A. gymnolobus could be considered as a promising source that contributes to the fight against cancer.

Exploring the Pharmacological Potential of Onosma riedliana: Phenolic Compounds and Their Biological Activities.

Onosma riedliana Binzet & Orcan, a traditionally used plant species, has been explored for its therapeutic potential in this study. The work presented here is the first report on the phenolic profile and biological activity of this species. Three extracts of varying polarity were prepared, with the methanolic extract containing the highest phenolic content (97.62 ± 0.20 mgGAE/g). Key phenolic compounds identified included pinoresinol, hesperidin, 4-hydroxybenzoic acid, and p-coumaric acid. The methanolic extract exhibited exceptional antioxidant properties, rivaling Trolox as a positive control, primarily attributed to hesperidin and luteolin. Moreover, the ethyl acetate extract demonstrated remarkable inhibition of cholinesterase and tyrosinase enzymes, while the methanolic extract displayed potent activity against carbohydrate hydrolytic enzymes, α-amylase and α-glucosidase. Again, phenolic compounds were shown to be responsible for the inhibition of cholinesterases and tyrosinase, but not for α-amylase and α-glucosidase. These findings underscore Onosma riedliana's potential for incorporation into diverse pharmaceutical formulations, given its multifaceted bioactivity.

Comparative docking and molecular dynamics studies of molnupiravir (EIDD-2801): implications for novel mechanisms of action on influenza and SARS-CoV-2 protein targets.

Molnupiravir (EIDD-2801) (MLN) is an oral antiviral drug for COVID-19 treatment, being integrated into viral RNA through RNA-dependent RNA polymerase (RdRp). Upon ingestion, MLN is transformed into two active metabolites: ß-d-N4-hydroxycytidine (NHC) (EIDD-1931) in the host plasma, and EIDD-1931-triphosphate (MTP) within the host cells. However, recent studies provide increasing evidence of MLN's interactions with off-target proteins beyond the viral genome, suggesting that the complete mechanisms of action of MLN remain unclear. The aim of this study was therefore to investigate the molecular interactions of MLN in the form of NHC and MTP with the non-RNA structural components of avian influenza (hemagglutinin, neuraminidase) and SARS-CoV-2 (spike glycoprotein, Mpro, and RdRp) viruses and to elucidate whether these two metabolites possess the ability to form stable complexes with these major viral components. Molecular docking of NHC and MTP was performed using AutoDock 4.2.6 and the obtained protein-drug complexes were submitted to 200-ns molecular dynamics simulations in triplicate with subsequent free energy calculations using GROMACS. Docking scores, molecular dynamics and MM/GBSA results showed that MTP was tightly bound within the active site of SARS-CoV-2 RdRp and remained highly stable throughout the 200-ns simulations. Besides, it was also shown that NHC and MTP formed moderately-to-highly stable molecular complexes with off-target receptors hemagglutinin, neuraminidase and Mpro, but rather weak interactions with spike glycoprotein. Our computational findings suggest that NHC and MTP may directly inhibit these receptors, and propose that additional studies on the off-target effects of MLN, i.e. real-time protein binding assays, should be performed.Communicated by Ramaswamy H. Sarma.

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.

Minerals, phenolics, and biological activity of wild edible mushroom, Morchella steppicola Zerova.

Tasteful morels (Morchella sp.) are one of the most popular mushrooms, both economically and scientifically. Due to their beneficial constituents, they are classified as functional foods. This study focuses on the chemical composition and biological activities of a wild edible mushroom, Morchella steppicola Zerova. The metal composition of this species reveals high levels of biogenic elements. However, according to the levels of iron and cobalt, and calculated health risk indices, this mushroom can be recommended for occasional consumption. Also, M. steppicola is found to be rich in gallic acid, protocatechuic acid, 4-hydroxybenzoic acid, and vanillic acid. Statistical analysis showed that mainly 4-hydroxybenzoic and vanillic acids are responsible for both antioxidant and inhibition of enzymes α-amylase and tyrosinase. Presented work acknowledges the fact that this mushroom has significant potential to be used for the treatment of several human disorders, similarly to other members of this genus.

Wild mushrooms from Ilgaz Mountain National Park (Western Black Sea, Turkey): element concentrations and their health risk assessment.

The purpose of this study was to determine Fe, Cd, Cr, Se, P, Cu, Mn, Zn, Al, Ca, Mg, and K contents of some edible (Chlorophyllum rhacodes, Clavariadelphus truncatus, Clitocybe nebularis, Hydnum repandum, Hygrophorus pudorinus, Infundibulicybe gibba, Lactarius deliciosus, L. piperatus, L. salmonicolor, Macrolepiota mastoidea, Russula grata, Suillus granulatus, and Tricholoma imbricatum), inedible (Amanita pantherina, Geastrum triplex, Gloeophyllum sepiarium, Hypholoma fasciculare, Phellinus vorax, Pholiota limonella, Russula anthracina, and Tapinella atrotomentosa), and poisonous mushroom species (Amanita pantherina and Hypholoma fasciculare) collected from Ilgaz Mountain National Park (Western Black Sea, Turkey). The element contents of the mushrooms were determined to be 18.0-1239.1, 0.2-4.6, 0.1-3.4, 0.2-3.2, 1.0-8.9, 3.3-59.9, 3.7-220.4, 21.3-154.1, 6.4-754.3, 15.8-17,473.0, 413.0-5943.0, and 2803.0-24,490.0 mg·kg-1, respectively. In addition to metal contents, the daily intakes of metal (DIM) and Health Risk Index (HRI) values of edible mushrooms were also calculated. Both DIM and HRI values of mushroom species except L. salmanicolor, M. mastoidea, and R. grata were within the legal limits. However, it was determined that the Fe content of L. salmanicolor and M. mastoidea and Cd content of R. grata were above the legal limits.

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.

Phytochemical Composition, Antioxidant, and Enzyme Inhibition Activities of Methanolic Extracts of Two Endemic Onosma Species.

Onosma species have been used as a dye for hundreds of years due to their dark red pigments. These species have also been used by mankind in the treatment of various diseases since ancient times. This work analyzed the phytochemical composition in methanol extract of two endemic Onosma species (O. lycaonica and O. papillosa). Methanolic extract of these species varied in the content of flavonoids and phenolics. The flavonoids were found higher in O. papillosa [32.9 ± 0.3 mg QEs (quercetin equivalent)/g extracts] while the phenolics were higher in O. lycaonica [43.5 ± 1.5 mg GAEs (gallic acid equivalent)/g extracts]. ESI-MS/MS (electrospray ionization-mass spectrometry) revealed the presence of 25 compounds in O. lycaonica and 24 compounds in O. papillosa. The former was richer than the latter for apigenin, luteolin, eriodictyol, pinoresinol, apigenin 7-glucoside, rosmarinic acid, luteolin 7-glucoside, ferulic acid, vanillin, caffeic acid, 4-hydroxybenzoic acid, (+)-catechin3,4-dihydroxyphenylacetic acid. The O. papillosa exhibited low EC50 (1.90 ± 0.07 mg/mL) which indicated its strong phosphomolybdenum scavenging activity as compared to O. lycaonica. However, the O. lycaonica showed low IC50 or EC50 for 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+), cupric reducing antioxidant power (CUPRAC), ferric reducing antioxidant power (FRAP) and ferrous ion chelating activity, as compared to O. papillosa. The results proved the presence of potent antioxidant compounds in O. lycaonica. Further, the plant extracts significantly varied for enzyme inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), but the plant extracts did not significantly differ for inhibition of α-glucosidase, α-amylase, and tyrosinase. Onosma species deserve further research towards developing novel drugs to treat oxidative diseases.

LC-MS/MS Profiles and In Vitro Biological Activities of Extracts of an Endemic Species from Turkey: Stachys cretica ssp. anatolica.

Background: Genus Stachys is one of the largest of the Lamiaceae family, having around 300 different plant species inhabiting areas with temperate and warm climates. The Stachys species in Turkey are represented with 81 taxa; 51 of them being endemic. Plants of the Stachys genus have been known for their biological activity and their use in ethnomedicine. Methods: The dominant components of S. cretica ssp. anatolica aqueous and methanol extracts were studied with the LC-MS/MS technique. Results: Chlorogenic acid, apigenin-7-glucoside and verbascoside present as the dominant polyphenols found in studied extracts. The prominent biological activity of the studied S. cretica ssp. anatolica methanol and aqueous extracts showed strong antioxidant activity and inhibition of enzymes tyrosinase and α-amylase, involved in skin disorders and diabetes mellitus type II. Conclusions: This study has proven that the aqueous and methanol extracts of S. cretica ssp. anatolica have prominent antioxidant activity, due to a high abundance of polyphenols. The strong antioxidant properties of S. cretica ssp. anatolica extracts show promising application for the pharmaceutical, food, and cosmetics industries.

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.

Cytotoxic and genotoxic evaluation of copper oxychloride through Allium test and molecular docking studies.

Copper oxychloride gained great importance due to its broad-spectrum antifungal action to combat various fungal diseases of plants. However, excess quantity of cupric fungicides on plants causes enzymatic changes and toxic effects. Thus, the current study was aimed to investigate the cytotoxicity and genotoxicity of copper oxychloride on Allium cepa root cells. The root growth, mitotic index (MI), chromosomal aberrations (CAs), and DNA damage were assessed through root growth inhibition, A. cepa ana-telophase, and alkaline comet assays. Furthermore, molecular docking was performed to evaluate binding affinities of two copper oxychloride polymorphs (atacamite and paratacamite) on DNA. In root growth inhibition test, onion root length was statistically significantly decreased by changing the copper oxychloride concentration from lower (2.64±0.11 cm) to higher (0.92±0.12 cm). Concentration- and time-dependent decrease in MI was observed whereas increase in CAs such as disturbed ana-telophase, chromosome laggards, stickiness, anaphase bridges, and DNA damage were caused by the copper oxychloride on A. cepa root cells. Molecular docking results revealed that the two main polymorphs of copper oxychloride (atacamite and paratacamite) bind selectively to G and C nucleotides on the B-DNA structure. It is concluded that the atacamite- and paratacamite-induced DNA damage may be through minor groove recognition and intercalation. Findings of the current study revealed the cytotoxic and genotoxic effects of copper oxychloride on A. cepa root cells. However, further studies should be carried out at the molecular level to reveal the cyto-genotoxic mechanism of action of copper oxychloride in detail.

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.

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.

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.

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.

Polyphenol Profile and Biological Activity Comparisons of Different Parts of Astragalus macrocephalus subsp. finitimus from Turkey.

The members of the genus Astragalus have great interest as traditional drugs in several folk systems including Turkey. In this sense, the present paper was aimed to explore the biological properties and chemical profiles of different parts (aerial parts, leaves, flowers, stems, and roots) of A. macrocephalus subsp. finitimus. Antioxidant (radical quenching, reducing power, and metal chelating) and enzyme inhibitory (α-amylase and tyrosinase) effects were investigated for biological properties. Regarding chemical profiles, individual phenolic compounds were detected by LC-MS, as well as total amounts. The leaves extract exhibited the strongest antioxidant abilities when compared with other parts. However, flowers extract had the best metal chelating ability. Hyperoside, apigenin, p-coumaric, and ferulic acids were identified as main compounds in the tested parts. Regarding enzyme inhibitory properties, tyrosinase inhibitory effects varied from IC50: 1.02 to 1.41 mg/mL. In addition, the best amylase inhibition effect was observed by leaves (3.36 mg/mL), followed by aerial parts, roots, stems, and flowers. As a result, from multivariate analysis, the tested parts were classified in three cluster. Summing up the results, it can be concluded that A. macrocephalus subsp. finitimus could be a precious source of natural bioactive agents in pharmaceutical, nutraceutical, and cosmeceutical applications.

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.