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Abstract: In the current study, in vitro neuroprotective effect of the ethyl acetate, methanol, and water extracts of Hypericum perforatum L. growing in Turkey was investigated through testing against acetylcholinesterase and butyrylcholinesterase at 50, 100, and 200μgmL−1, linked to Alzheimer''s disease, and tyrosinase at 250μgmL−1, related to Parkinson''s disease. As neurodegeneration is strongly correlated with oxidative damage and metal accumulation, antioxidant activity of the extracts was determined by radical scavenging assays against 2,2-diphenyl-1-picrylhydrazyl (DPPH), N,N-dimethyl-p-phenylendiamine (DMPD), super oxide, and nitric oxide radicals, as well as metal-chelation capacity, ferric- (FRAP), and phosphomolibdenum-reducing antioxidant power (PRAP). Total phenol and flavonoid quantities of the extracts were also determined. The methanol extract showed the highest acetylcholinesterase inhibition (49.54±4.44%), while the ethyl acetate extract had the best inhibition towards butyrylcholinesterase (50.79±3.07%). Only the methanol extract showed low tyrosinase inhibition (19.21±1.44%). In the antioxidant assays, the methanol extract had a greater activity in general. [Copyright &y& Elsevier]

The dichloromethane (DCM), acetone, ethyl acetate and methanol extracts of the leaves and berries of Myrtus communis L. were screened against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase (TYRO), the enzymes linked to neurodegenerative diseases, at 200 μg ml− 1. Antioxidant activity was tested using radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and N, N- dimethyl- p-phenylenediamine (DMPD) radicals, metal chelation capacity, ferric-reducing antioxidant power (FRAP) and phosphomolybdenum-reducing antioxidant power (PRAP) assays. Total phenol and flavonoid quantification of the extracts was calculated spectrophotometrically. The extracts showed a moderate AChE (17.49 ± 3.99% to 43.15 ± 1.55%) and TYRO inhibition (4.48 ± 1.50% to 40.53 ± 0.47%). The leaf extracts were ineffective against BChE, while the berry extracts displayed inhibition between 21.83 ± 3.82% and 36.80 ± 2.00%. The polar extracts exerted remarkable scavenging effect against DPPH and DMPD and also in the FRAP assay, where the DCM extract of the berries had the best metal chelation capacity (79.29 ± 1.14%). This is the first study that demonstrates in vitro neuroprotective effects of myrtle. [ABSTRACT FROM AUTHOR]

Objective: The dichloromethane, acetone, ethyl acetate, and methanol extracts of the cones and leaves of Cupressus sempervirens var. horizantalis (CSH) and var. pyramidalis (CSP) were investigated for their in vitro neurobiological effects. Methods: The extracts were screened for their inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase (TYRO) enzymes using microtiter plate assays. Antioxidant activity of the extracts was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and N,N-dimethyl-p-phenylendiamine (DMPD) radical scavenging activity, metal-chelation capacity along with ferric-(FRAP) and phosphomolibdenumreducing antioxidant power (PRAP) tests. Total phenol and flavonoid contents of the extracts were calculated spectrophotometrically. Results: The extracts displayed weak to moderate cholinesterase inhibition at 200 μg mL-1. The cone dichloromethane extract of CSP showed the highest inhibition (36.10±1.45%) against AChE, while the best inhibition (40.01±0.77%) against BChE was caused by the leaf acetone extract of CSH. Conclusion: Antioxidant activity of the extracts was observed to vary according to the method used. This is the first study describing anticholinesterase and antityrosinase effects of the varieties of C. sempervirens. [ABSTRACT FROM AUTHOR]

Abstract: Various herbal coffee varieties are consumed traditionally in Turkey. In the current study, the ethanol extracts of the coffee and seed samples obtained from Gundelia tournefortii (tumble thistle), Nigella sativa (black cumin), Phoenix dactylifera (date), and Ceratonia siliqua (carob) as well as a sample of instant coffee (Nescafe®, green blend) were tested against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase, the enzymes connected to neurodegeneration. Since oxidative stress is strongly associated with neurodegeneration, antioxidant activity of the extracts was also determined. Antioxidant activity of the extracts was measured using anti-radical and metal-related methods. Total phenol and flavonoid contents were calculated using Folin–Ciocalteau''s and AlCl3 reagents, respectively. Fatty acid compositions of the seed oils of tumble thistle and black seed were analyzed by GC–MS. Our results showed that the date sample exerted the highest AChE and BChE inhibition at 300μgmL−1 (52.96% and 83.22%, respectively). [Copyright &y& Elsevier]

The genus Iris is known to contain gorgeous lowers with a violet-like scent. Iris is represented in the Turkish flora by 37 species. Nonetheless, no study has been so far performed on the volatile constituents of the Turkish Iris species. In this study, our objective was to determine compositions of volatiles of the individual plant parts, including lowers, rhizomes, and stems of three Turkish Iris species, namely: I. pseudacorus L. collected from two different localities (Beyşehir and Trabzon), I. kerneriana Asch. & Sint. ex Baker, as well as I. sofarana Foster (cultivated) by microdistillation. The volatile compounds of these species were analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) systems, simultaneously. The main components were characterized as follows: I. pseudacorus lowers: hexadecanoic acid (30.3%), heptacosane (13.6%), 6-methyl-5-hepten-2-one (11%); I. pseudacorus rhizomes: nonacosane (37.3%), triacontane (9.0%), octacosane (7.9%), pentacosane (7.7%); I. kerneriana lowers: α-kessyl acetate (14.7%), longipinene (10.8%), decanoic acid (10.6%), heptacosane (10.2%), hexadecanoic acid (9.5%), 6-methyl-5-hepten-2-one (7.1%); I. kerneriana rhizomes: tetradecanoic acid (31.5%), heptacosane (10.0%), ş-kessyl acetate (9.5%), nonacosane (8.8%), 6-methyl-5-hepten-2-one (7.7%); I. kerneriana stems: nonacosane (18.3%), heptacosane (16.7%), pentacosane (10.3%), tricosane (6.0%); I. pseudoacarus rhizomes: nonacosane (26.2%), α-Kessyl acetate (14.7%), triacontane (7.3%), octacosane (7.4%); I. pseudacorus stems: octyl acetate (32.0%), nonacosane (14.4%), octyl butyrate (9.5%); I. sofarana rhizomes: decanoic acid (11.7%), α-pinene (8.4%), ethyl oleate (7.6%), irone (5.7%). [ABSTRACT FROM AUTHOR]

Cholinesterase (ChE) inhibition is an important treatment strategy for Alzheimer's disease (AD) as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are involved in the pathology of AD. In the current work, ChE inhibitory potential of twenty-four natural products from different chemical classes (i.e., diosgenin, hecogenin, rockogenin, smilagenin, tigogenin, astrasieversianins II and X, astragalosides I, IV, and VI, cyclocanthosides E and G, macrophyllosaponins A-D, kokusaginin, lamiide, forsythoside B, verbascoside, alyssonoside, ipolamide, methyl rosmarinate, and luteolin-7-O-glucuronide) was examined using ELISA microtiter assay. Among them, only smilagenin and kokusaginine displayed inhibitory action against AChE (IC50 = 43.29 ± 1.38 and 70.24 ± 2.87 µg/mL, respectively). BChE was inhibited by only methyl rosmarinate and kokusaginine (IC50 = 41.46 ± 2.83 and 61.40 ± 3.67 µg/mL, respectively). IC50 values for galantamine as the reference drug were 1.33 ± 0.11 µg/mL for AChE and 52.31 ± 3.04 µg/mL for BChE. Molecular docking experiments showed that the orientation of smilagenin and kokusaginine was mainly driven by the interactions with the peripheral anionic site (PAS) comprising residues of hAChE, while kokusaginine and methyl rosmarinate were able to access deeper into the active gorge in hBChE. Our data indicate that similagenin, kokusaginine, and methyl rosmarinate could be hit compounds for designing novel anti-Alzheimer agents. [ABSTRACT FROM AUTHOR]

Background The outbreak of coronavirus disease 2019 (COVID-19) has spread worldwide and continues to threaten peoples' health as well as put pressure on the accessibility of medical systems. Early prediction of survival of hospitalized patients will help in the clinical management of COVID-19, but a prediction model that is reliable and valid is still lacking. Methods We retrospectively enrolled 628 confirmed cases of COVID-19 using positive RT-PCR tests for SARS-CoV-2 in Tongji Hospital, Wuhan, China. These patients were randomly grouped into a training (60%) and a validation (40%) cohort. In the training cohort, LASSO regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of patients with COVID-19. A nomogram based on the 3 variables was built for clinical use. AUCs, concordance indexes (C-index), and calibration curves were used to evaluate the efficiency of the nomogram in both training and validation cohorts. Results Hypertension, higher neutrophil-to-lymphocyte ratio, and increased NT-proBNP values were found to be significantly associated with poorer prognosis in hospitalized patients with COVID-19. The 3 predictors were further used to build a prediction nomogram. The C-indexes of the nomogram in the training and validation cohorts were 0.901 and 0.892, respectively. The AUC in the training cohort was 0.922 for 14-day and 0.919 for 21-day probability of in-hospital survival, while in the validation cohort this was 0.922 and 0.881, respectively. Moreover, the calibration curve for 14- and 21-day survival also showed high coherence between the predicted and actual probability of survival. Conclusions We built a predictive model and constructed a nomogram for predicting in-hospital survival of patients with COVID-19. This model has good performance and might be utilized clinically in management of COVID-19. [ABSTRACT FROM AUTHOR]

• Four compounds were isolated from the plant with activity-guided fractionation. • All the ligands can be regarded as inhibitor candidates with fair binding energies. • Methyl gallate and astragalin were predicted as non-mutagenic. • Cotinus coggygria would be a suitable raw herbal material for cosmetic products. Cotinus coggygria Scop. (Anacardiaceae, syn: Rhus cotinus L.) is known as "boyacı sumağı, sarı boya, duman ağacı" in Turkish and "smoke tree" in English. It is commonly grown in Southern Europe and Anatolia. The leaves have been used due to its antiseptic, hemostatic, antipyretic, and wound healing effects as a 5% infusion in traditional medicine. It has also been reported to be used against skin disorders in Russia. Based on this information, the ethanol extracts prepared from the pedicels and leaves of C. coggygria were investigated for their elastase, collagenase, and tyrosinase inhibitory effects, which are enzymes related to anti-aging, using ELISA microtiter assays. Based on our results, the ethanol extracts prepared from the leaves and pedicels of C. coggygria had low elastase (28.16% ± 2.91 and 25.76% ± 1.71, respectively), moderate collagenase (47.78% ± 4.90 and 46.51% ± 3.15, respectively), and tyrosinase (57.94% ± 0.67 and 46.20% ± 0.92, respectively) inhibition at final concentration (666 µg/mL). The ethanol extract prepared from the pedicels of C. coggygria was subjected to bioactivity-guided fractionation, which led to isolation of methyl gallate, astragalin, isoquercetin, and hyperoside from the active fractions. In addition to the enzyme assays, in order to understand the inhibition mechanisms of the compounds inside the ligand-binding domains, the interactions were simulated and the key amino acids contributing to the hydrogen bonds and non-polar interactions with the ligands were reported. [ABSTRACT FROM AUTHOR]

Twelve undescribed triterpenoid pentacyclic glycosides, medicagenic acid (3- O -β-D-glucuronopyranosyl-28- O -{[β-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-[α-L-rhamnopyranosyl-(1 → 3)]-4- O -acetyl-β-D-fucopyranosyl-(1→)}-2β,3β-dihydroxyolean-12-ene-23,28-dioic acid, 3- O -β-D-glucuronopyranosyl-28- O -{[α-L-rhamnopyranosyl-(1 → 2)]-[β-D-apiofuranosyl-(1 → 3)]-4- O -acetyl-β-D-fucopyranosyl-(1→)}-2β,3β-dihydroxyolean-12-ene-23,28-dioic acid, 3- O -β-D-glucuronopyranosyl-28- O -{[α-L-rhamnopyranosyl-(1 → 2)]-3,4- O -diacetyl-β-D-fucopyranosyl-(1→)}-2β,3β-dihydroxyolean-12-ene-23,28-dioic acid, 28- O -{[6- O -acetyl-β-D-glucopyranosyl-(1 → 2)]-[2- O -acetyl-α-L-rhamnopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 6)]-β-D-glucopyranosyl-(1→)}-2β,3β-dihydroxyolean-12-ene-23,28-dioic acid, 28- O -{[6- O -acetyl-β-D-glucopyranosyl-(1 → 2)]-[3- O -acetyl-α-L-rhamnopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 6)]-β-D-glucopyranosyl-(1→)}-2β,3β-dihydroxyolean-12-ene-23,28-dioic acid, 28- O -{[6- O -acetyl-β-D-glucopyranosyl-(1 → 2)]-[4- O -acetyl-α-L-rhamnopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 6)]-β-D-glucopyranosyl-(1→)}-2β,3β-dihydroxyolean-12-ene-23,28-dioic acid, 28- O -{[6- O -acetyl-β-D-glucopyranosyl-(1 → 2)]-[β-D-glucopyranosyl-(1 → 6)]-β-D-glucopyranosyl-(1→)}-2β,3β-dihydroxyolean-12-ene-23,28-dioic acid, 28- O- {[β-D-glucopyranosyl-(1 → 2)]-[β-D-glucopyranosyl-(1 → 6)]-β-D-glucopyranosyl-(1→)}-2β,3β-dihydroxyolean-12-ene-23,28-dioic acid), zanhic acid (3- O -β-D-glucuronopyranosyl-28- O -{[β-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-[α-L-rhamnopyranosyl-(1 → 3)]-4- O -acetyl-β-D-fucopyranosyl-(1→)}2β,3β,16α-trihydroxyolean-12-ene-23,28-dioic acid, 3- O -β-D-glucuronopyranosyl-28- O -{[β-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-β-D-fucopyranosyl-(1→)}-2β,3β,16α-trihydroxyolean-12-ene-23,28-dioic acid), 29-hydroxy-medicagenic acid (3- O -β-D-glucuronopyranosyl-28- O -{[β-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)]-[α-L-rhamnopyranosyl-(1 → 3)]-4- O -acetyl-β-D-fucopyranosyl-(1→)}-2β,3β,29β-trihydroxyolean-12-ene-23,28-dioic acid) and herniaric acid (28- O -{[6- O -acetyl-β-D-glucopyranosyl-(1 → 2)]-[α-L-rhamnopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 6)]-β-D-glucopyranosyl-(1→)}-2β,3β-dihydroxyolean-18-ene-23,28-dioic acid) were isolated from the whole plant extract of Herniaria glabra L. (Caryophyllaceae), wild growing in the Ukraine. In addition, five known triterpenoid saponins; i.e. herniariasaponins 1, 4, 5, 6, and 7 were also isolated. Their structures were elucidated by HRESIMS, 1D and 2D NMR spectroscopy, as well as by comparison with the literature data. Twelve herniariasaponins, the purified crude extract, and the saponin fraction were evaluated in vitro for their xanthine oxidase, collagenase, elastase, and tyrosinase inhibitory activity. Moreover, herniariasaponins 4, 5, and 7 were screened for their cholinesterase inhibitory potential. As a result, no or low inhibition towards the mentioned enzymes was observed. Image 1 • Twelve undescribed herniariasaponins were isolated from Herniaria glabra L. • Two undescribed pentacyclic triterpenoid aglycones were discovered. • Tested samples showed no or low enzyme inhibitory activities in vitro. • The target enzymes were xanthine oxidase, collagenase, elastase, tyrosinase, ChE. [ABSTRACT FROM AUTHOR]

Abstract The Hedgehog pathway is essential for embryonic development but also for tissue and organ homeostasis in adult organisms. Activation of this pathway leads to the expression of target genes involved in proliferation, angiogenesis and stem cell self-renewal. Moreover, abnormal persistence of Hedgehog signaling is directly involved in a wide range of human cancers. Development of novel strategies targeting the Hedgehog pathway has become a subject of increased interest in anticancer therapy. These data are sustained by pre-clinical studies demonstrating that Hedgehog pathway inhibitors could represent an effective strategy against a heterogeneous panel of malignancies. Limited activity in other tumor types could be explained by the existence of crosstalk between the Hedgehog pathway and other signaling pathways that can compensate for its function. This review describes the Hedgehog pathway in detail, with its physiological roles during embryogenesis and adult tissues, and summarizing the preclinical evidence on its inhibition, the crosstalk between Hedgehog and other cancer-related pathways and finally the potential therapeutic effects of emerging compounds. [ABSTRACT FROM AUTHOR]

Although biological and pharmacological effects of dietary natural products have been intensively studied, there has been no bibliometric analysis performed on this research field up to now. The current study has aimed to identify and analyze the manuscripts on dietary natural products and their potential to influence health and disease including studies using animal models. Data, including words from titles and abstracts, publication and citation data, have been extracted from Web of Science database and analyzed by the VOSviewer software. Our search has yielded 1,014 manuscripts. The ratio of original articles to reviews was identified to be 1.5:1. Over half of the manuscripts have been published since 2010. The manuscripts have been contributed by 4,301 authors from 1,445 organizations in 76 countries/territories and published in 499 journals. The results from the current study point out that scientific research focusing on the potential of dietary natural products to affect health and disease status (including animal model studies) is expanding, and suggests an increasing significance of this scientific area. With the progressive development and improvement of animal studies, it should be expected that animal models of different human diseases (especially civilization ones) would be an integral part of the research for the evaluation of pharmaceuticals originated from dietary natural products like plants or plant materials. Moreover, natural products can also be fed to animals to improve the quality of animal products, with numerous resulting functional effects. [ABSTRACT FROM AUTHOR]

Artemisinin (ART) is a bioactive compound isolated from the plant Artemisia annua and has been traditionally used to treat conditions such as malaria, cancer, viral infections, bacterial infections, and some cardiovascular diseases, especially in Asia, North America, Europe and other parts of the world. This comprehensive review aims to update the biomedical potential of ART and its derivatives for treating human diseases highlighting its pharmacokinetic and pharmacological properties based on the results of experimental pharmacological studies in vitro and in vivo. Cellular and molecular mechanisms of action, tested doses and toxic effects of artemisinin were also described. The analysis of data based on an up-to-date literature search showed that ART and its derivatives display anticancer effects along with a wide range of pharmacological activities such as antibacterial, antiviral, antimalarial, antioxidant and cardioprotective effects. These compounds have great potential for discovering new drugs used as adjunctive therapies in cancer and various other diseases. Detailed translational and experimental studies are however needed to fully understand the pharmacological effects of these compounds. [Display omitted] • Artemisinin (ART) is a bioactive compound isolated from the plant Artemisia annua. • ART has a great therapeutic potential for treating human chronic diseases. • Studies confirmed the effects in malaria, cancer, viral , bacterial infections and cardiovascular diseases. • ART has potential when is used as adjunctive therapies in cancer and other diseases. [ABSTRACT FROM AUTHOR]

Plant extracts have been long used by the traditional healers for providing health benefits and are nowadays suitable ingredient for the production of formulated health products and nutraceuticals. Traditional methods of extraction such as maceration, percolation, digestion, and preparation of decoctions and infusions are now been replaced by advanced extraction methods for increased extraction efficiency and selectivity of bioactive compounds to meet up the increasing market demand. Advanced techniques use different ways for extraction such as microwaves, ultrasound waves, supercritical fluids, enzymes, pressurized liquids, electric field, etc. These innovative extraction techniques, afford final extracts selectively rich in compounds of interest without formation of artifacts, and are often simple, fast, environment friendly and fully automated compared to existing extraction method. The present review is focused on the recent trends on the extraction of different bioactive chemical constituents depending on the nature of sample matrices and their chemical classes including anthocyanins, flavonoids, polyphenols, alkaloids, oils, etc. In addition, we review the strategies for designing extraction, selection of most suitable extraction methods, and trends of extraction methods for botanicals. Recent progress on the research based on these advanced methods of extractions and their industrial importance are also discussed in detail. [ABSTRACT FROM AUTHOR]

Melanoma is the most deadly form of skin cancer, with about 48,000 deaths each year worldwide. Growing evidence suggests that individual nutrients or dietary patterns might have important roles in the prevention of melanoma. Considering that melanoma is a potentially life-threatening cancer, novel protective and adjuvant treatments are needed to improve its prognosis. Curcumin is a bioactive substance extracted from rhizome ofCurcuma longaL. Its global market is expected to grow in the next few years, especially in the pharmaceutical industry, due to its numerous physiological and pharmacological properties. For this review, we collected the available data on the protective and therapeutic role of curcumin against melanoma. We also discuss the chemistry, dietary sources, bioavailability, and metabolism of curcumin, and the mechanisms of action of its potential anticancer effects at the molecular level. Current challenges and future directions for research are also critically discussed. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases e.g. Alzheimer's disease (AD) and Parkinson's disease (PD) are on increase particularly among elderly population and the drugs available are only able to provide symptomatic treatment. Hence, an extensive research is still being conducted for developing new drugs toward these diseases. In the present study, we have focused on a Turkish medicinal plant, Phlomis grandiflora var. grandiflora (Lamiaceae) in order to assess its potential memoryenhancing effect. On this purpose, the methanol and ethanol extracts of the aerial parts of P. grandiflora var. grandiflora and the fractions (hexane, chloroform, ethyl acetate and n-butanol) from the ethanol extract were subjected to several enzyme inhibitory assays including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), which are related to AD treatment as well as tyrosinase (TYR) as a target for the treatment of PD toxicity. Among the tested extracts, only the chloroform fraction exerted a perceptible inhibition against BChE (59.38 ± 2.28%) at 200 μg/mL. The ethyl acetate and n-butanol fractions displayed clearly a stronger quenching activity (over 80%) against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radicals, whereas all of them were observed with a lower activity (below 22%) against N,N-dimethyl-pphenylendiamine (DMPD) radical. On the other hand, more polar extracts and fractions were the most active in ferric- (FRAP) and phosphomolibdenum-reducing antioxidant power (PRAP) assays, while the main extracts possessed a higher metal-chelation capacity. HPLC analysis on the ethanol and methanol extracts was shown to be rich in phenolic acids, although their quantity varied remarkably in these extracts. Our findings pointed out to the chloroform fraction with promising BChE-inhibitory effect. [ABSTRACT FROM AUTHOR]

In this study, cytotoxic effects of the dichloromethane, ethyl acetate, ethanol, and aqueous extracts of the aerial parts of Cyclotrichium niveum (Boiss.) Manden. & Scheng (Lamiaceae) were evaluated. We tested HeLa, MCF-7 cancer cells, and MRC-5 and MCF-10A normal cells. The ethyl acetate and dichloromethane extracts induced cytotoxicity whereas the ethanol and aqueous extracts had no cytotoxic activity against both cancer cells. IC 50 values of the dichloromethane extract were 353.0 ± 84.30 μg/ml, 114.8 ± 40.34 μg/ml, 39 ± 0.56 μg/ml, and 49 ± 13 μg/ml in HeLa, MCF-7, MRC-5, MCF-10A cells, respectively. IC 50 values of the ethyl acetate extract were 117.0 ± 36.24 μg/ml in HeLa cells, 156.3 ± 19.86 μg/ml in MCF-7 cells, 1100 ± 340 μg/ml in MRC-5 cells and 7900 ± 1200 μg/ml in MCF-10A cells. Additionally, the ethyl acetate extract showed more selectivity to HeLa and MCF-7 cancer cells than MRC-5 and MCF-10A normal cells. Our results of HPLC analysis showed that apigenin in the ethyl acetate extract (2.2518 ± 0.0005 mg/100 mg extract) might be responsible of that selective cytotoxic effect. In the current work, we have shown for the first time that C. niveum has cytotoxic properties in the cancer cell lines tested. [ABSTRACT FROM AUTHOR]

Eugenol is a hydroxyphenyl propene, naturally occurring in the essential oils of several plants belonging to theLamiaceae,Lauraceae,Myrtaceae, andMyristicaceaefamilies. It is one of the major constituents of clove (Syzygium aromaticum(L.) Merr. & L.M. Perry,Myrtaceae) oil and is largely used in both foods and cosmetics as a flavoring agent. A large body of recent scientific evidence supports claims from traditional medicine that eugenol exerts beneficial effects on human health. These effects are mainly associated with antioxidant and anti-inflammatory activities. Eugenol has also shown excellent antimicrobial activity in studies, being active against fungi and a wide range of gram-negative and gram-positive bacteria. The aim of this review is to analyze scientific data from the main published studies describing the antibacterial and antifungal activities of eugenol targeting different kind of microorganisms, such as those responsible for human infectious diseases, diseases of the oral cavity, and food-borne pathogens. This article also reports the effects of eugenol on multi-drug resistant microorganisms. On the basis of this collected data, eugenol represents a very interesting bioactive compound with broad spectrum antimicrobial activity against both planktonic and sessile cells belonging to food-decaying microorganisms and human pathogens. [ABSTRACT FROM AUTHOR]

The absolute configurations of the known but unusual spiro-flavostilbenoids found in the bark of Yucca schidigera Roezl ex Ortgies, were determined by applying time-dependent density functional theory simulation of electronic circular dichroism spectra. The absolute configurations obtained were as follows: (2 S ,3 R) for yuccaol A, yuccaol D and yuccalide A; (2 S ,3 S) for yuccaol B, yuccaol C and yuccaol E; (2 S ,3 S ,2′ S ,3′ S) for gloriosaol A; (2 S ,3 R ,2′ S ,3′ R) for gloriosaol C; (2 S ,3 S ,2′ S ,3′ R) for gloriosaol D; (2 S ,3 R ,2′ S ,3′ S) for gloriosaol E. These findings indicate that the compounds are all biosynthetic derivatives either of (2 R)-naringenin and trans -resveratrol or of trans -3,3 ′ ,5,5 ′ -tetrahydroxy-4′-methoxystilbene. In contrast, gloriosaols are direct derivatives of yuccaols (note that substituting by stilbenoid changes the absolute configuration of C-2 naringenin carbon to 2 S). A putative mechanism for their biosynthesis is proposed taking into account key aspects of regio- and stereoselectivity. Yuccaol B and gloriosaol A showed in vitro moderate inhibitory effects against acetyl-/butyrylcholinesterases (AChE/BChE) with IC 50 values of 43/81 and 45/65 μM respectively. The selectivity index values calculated from the IC 50 values of BChE and AChE were 1.9 and 1.4. Molecular docking simulations showed their interaction with the peripheral anionic site of human AChE and the catalytic site of the human BChE. [Display omitted] • The absolute configurations of spiro-flavostilbenoids from Y. schidigera were elucidated. • Their biosynthetic origin from unusual (2 R)-naringenin was proposed. • Yuccaol B and gloriosaol A showed moderate in vitro AChE/BChE inhibitory activities. • Molecular docking of yuccaol B and gloriosaol A to hAChE/hBChE was performed. [ABSTRACT FROM AUTHOR]

Cholinesterase inhibition is one of the most treatment strategies against Alzheimer's disease (AD) where metal accumulation is also strongly associated with pathology of the disease. In the current study, we assessed inhibitory effect against acetyl- (AChE) and butyrylcholinesterase (BChE) and metal-chelating capacity of twelve diterpenes: arucadiol, miltirone, tanshinone IIa, 1-oxomiltirone, cryptotanshinone, 1,2-didehydromiltirone, 1,2-didehydrotanshinone IIa, 1β-hydroxycryptotanshinone, 15,16- dihydrotanshinone, tanshinone I, isotanshinone II, 1(S)-hydroxytanshinone IIa, and rosmarinic acid, isolated from Perovskia atriplicifolia and Salvia glutinosa. The compounds were tested at 10 μg/mL using ELISA microtiter assays against AChE and BChE. QSAR and molecular docking studies have been also performed on the active compounds. All of the compounds showed higher [e.g., IC50 = 1.12 ± 0.07 mg/mL for 1,2-didehydromiltirone, IC50 = 1.15 ± 0.07 mg/mL for cryptotanshinone, IC50 = 1.20 ± 0.03 μg/mL for arucadiol, etc.)] or closer [1,2-didehydrotanshinone IIa (IC50 = 5.98 ± 0.49 μg/mL) and 1(S)-hydroxytanshinone IIa (IC50 = 5.71 ± 0.27 μg/mL)] inhibition against BChE as compared to that of galanthamine (IC50 = 12.56 ± 0.37 μg/mL), whereas only 15,16-dihydrotanshinone moderately inhibited AChE (65.17 ± 1.39%). 1,2-Didehydrotanshinone IIa (48.94 ± 0.26%) and 1(S)-hydroxytanshinone IIa (47.18 ± 5.10%) possessed the highest metal-chelation capacity. The present study affords an evidence for the fact that selective BChE inhibitors should be further investigated as promising candidate molecules for AD therapy. [ABSTRACT FROM AUTHOR]

• Synthesis of S-benzyl dithiocarbamates derivatives via a single pot reaction setup. • Characterization of synthesized derivatives via NMR (1H and 13C), FT-IR and high resolution mass spectrometry. • In vitro enzyme inhibition assays against cholinesterase enzyme and monoamine oxidase. • Comprehensive in-silico investigations of synthesized derivatives. The current study was aimed to identify the selective and multi-targeted inhibitors of cholinesterase and monoamine oxidase enzymes. For this purpose, a novel class of multi-targeted compounds i.e., S -benzyl dithiocarbamates (1-30) was synthesized via a single pot reaction and the structures were characterized via NMR (1H and 13C), FT-IR and high-resolution mass spectrometry (HRMS). Moreover, the purity of the final products was determined using thin-layer chromatography (TLC). The compounds were evaluated for their inhibitory potential against cholinesterases (ChE) and monoamine oxidases (MAO). Among all derivatives, compound 5 (2-(trifluoromethyl) benzyl azepane-1-carbodithioate) depicted the maximum inhibition of AChE and BChE enzyme with an IC 50 value of 4.37±0.94 and 14.9±1.11, respectively. The derivative 11, expressed maximum inhibition of MAO-A and MAO-B with an IC 50 value of 1.14±0.03 and 1.01 ± 0.16 µM, respectively. Whereas, compound 16 exhibited maximum inhibitory potential against all four targeted enzymes i.e., AChE, BChE, MAO-A and MAO-B with an IC 50 value of 1.39±0.07 µg/ mL, 1.52±0.14 µg/ mL, 44.9±1.54 µM and 2.85±0.21 µM, respectively. The chemical reactivity profile of the potent derivatives were evaluated through density functional theory studies (DFT) where it was found that compound 5, 6 and 11 possessed reactive character due to narrow LUMO/HOMO energy gap. In addition, Molecular docking studies revealed excellent docking scores and produced sable protein-ligand complexes. The stability of protein-ligand complex was affirmed by molecular dynamic simulations which revealed stable and equilibrated trajectories of simulated complexes. The findings of in-vitro and in-silico studies suggested compound 16 as a promising multi-targeted compound that can be act as lead molecule for the treatment of AD. [Display omitted] [ABSTRACT FROM AUTHOR]

The ethanol (EtOH) extracts of thirty-four taxa from the Amelanchier , Cotoneaster , Pyrus , and Sorbus genera (Rosaceae) have been screened for their inhibitory potential against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at 200 μg/mL as well as their antioxidant activity using metal-chelating capacity, ferric-reducing antioxidant power (FRAP), and N , N -dimethyl- p -phenylenediamine (DMPD) radical scavenging activity at 2000 μg/mL using ELISA microtiter assays. Our results indicated that two extracts of Sorbus umbelleta from different localities had 56.20 ± 5.05% (IC 50 = 182.1 μg/mL) and 58.18 ± 3.77% (IC 50 = 177.8 μg/mL) of inhibition against AChE, while 50.67 ± 0.32% of BChE inhibition (IC 50 = 206.5 μg/mL) was caused by the extract of Cotoneaster meyeri . Among the tested extracts, S. subfusca displayed the highest FRAP value (1.618 ± 0.09) and DMPD radical scavenging activity (31.05 ± 0.01%), while the best metal-chelating capacity (27.13 ± 2.01%) was found to belong to the extract of Sorbus kusnetzovii . The EtOH extracts of the active species ( e.g. Cotoneaster meyeri , two samples of Sorbus umbelleta , and Sorbus subfusca ) in enzyme inhibition assays have also been subjected to HPLC analysis to quantify some selected phenolic acids and flavonoid derivatives. Chlorogenic acid (28.83 ± 0.67–149.10 ± 0.46 mg/100 g) and rutin (46.08 ± 0.63–109.08 ± 0.07 mg/100 g) were quantified in all four extracts. Caffeic acid (0.79 ± 0.18 mg/100 g) was only present in C. meyeri , whereas ferulic acid and apigenin were detected in three extracts in minor amounts. Our findings also pointed out to a marked variation in bioactivity and phytochemistry among the same plant species growing in different places. This is the first anticholinesterase and antioxidant study on most the Rosaceae species studied herein. Among them, Sorbus umbellata appears to be a promising herb due to its noticeable anti-AChE and antioxidant activities. [ABSTRACT FROM AUTHOR]

Cataracts, glaucoma, and age-related macular degeneration are known as major ocular problems which cause blindness among the elderly population worldwide. Oxidative stress plays an important role in both the initiation and progression of ocular problems and with respect to this; dietary antioxidants can serve as a therapeutic strategy for the improvement of ocular health. Zeaxanthin is known as one of the most important and common xanthophyll carotenoids, possessing multiple therapeutic effects such as strong antioxidant and pro-oxidant behaviour as well as anti-inflammatory effects. A growing body of literature shows that zeaxanthin mitigates ocular problems and suppresses oxidative stress in the retinal tissues. This paper aims to critically review the available literature regarding the beneficial effects of zeaxanthin on ocular problems with emphasis on its chemistry, bioavailability, and sources. [ABSTRACT FROM AUTHOR]

The hydroalcoholic extracts of the Turkish traditional coffee samples from 18 commercial brands were tested for their neurobiological effects through enzyme inhibition based on enzyme-linked immunosorbance microtiter assays against acetylcholinesterase, butyrylcholinesterase, and tyrosinase, linked to Alzheimer's and Parkinson's diseases. The extracts were also subjected to several antioxidant test systems to define their antiradical, metal-chelation capacity, and reducing power. Total phenol and flavonoid contents in the extracts were delineated by spectrophotometric methods, while chlorogenic acid in the coffee samples was quantified by high-pressure liquid chromatography. The extracts displayed low to moderate inhibition (from 2.13 ± 0.01% to 36.12 ± 1.07% at 200 mg/mL) against the tested enzymes, whereas they had notable 2,20-diphenyl-1-picrylhydrazyl radical scavenging activity up to 56.15 ± 2.03% at 200 mg/mL. The extracts exerted a remarkable ferric-reducing antioxidant power values, while chlorogenic acid was found to range between 0.288 ± 0.005% and 2.335 ± 0.010%. [ABSTRACT FROM AUTHOR]

The World Health Organization estimated that the proportion of older people (over 60 years) will increase from 11% to 22% during next 40 years throughout the world. With respect to this, the morbidity and mortality rates of age-related diseases will increase. Mental diseases are the most common and important health problems among elderly people. Therefore, much attention has been paid to the discovery of neuroprotective drugs with high efficacy and negligible adverse effects. A growing body of scientific evidence has shown that phytochemicals possess neuroprotective effects and also mitigate neurodegeneration under both in vivo and in vitro conditions. Polyphenolic compounds, especially flavonoids, are known as most common chemical class of phytochemicals which possess a multiple range of health promoting effects. Chrysin, belonging to the flavone class, is one of the most important bioactive constituents of different fruits, vegetables and even mushrooms. Chrysin possesses potent neuroprotective effects and suppress neuroinflammation. In addition, chrysin improves cognitive decline and possesses a potent anti-amyloidogenic and neurotrophic effects. Furthermore, beneficial effects of chrysin on both depression and epilepsy have been reported. The present paper aimed to critically review the available literature data regarding the neuroprotective effects of chrysin as well as its chemistry, sources and bioavailability. [ABSTRACT FROM AUTHOR]

The article highlights study which provided supplementary content in response to some of the researchers' valuable comments, which will aid the understanding. It discusses that the transparent reporting of a multivariable prediction model for individual prognosis of diagnosis (TRIPOD) Statement, providing a detailed framework for reporting prediction models, has guided work.

In the current study, the aqueous, dichloromethane, and methanol extracts of 12 samples of Viscum album L. collected on different host plants as well as two isolated compounds [syringin (VA-1) and 5,7-dimethoxyflavanone-4′- O -[5′′′- O - trans -cinnamoyl-β- d -apiofuranosyl]-β- d- glucopyranoside (VA-2)] were tested against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tryosinase (TYRO) enzymes at 2000 μg/mL by ELISA microtiter plate assays. Antioxidant activity of the extracts and compounds was evaluated by six in vitro methods [2,2-diphenyl-1-picrylhydrazyl (DPPH), N,N -dimethyl- p -phenylendiamine (DMPD), and nitric oxide radical scavenging assays, metal-chelation capacity, ferric-(FRAP), and phosphomolibdenum-reducing antioxidant power (PRAP)]. Total phenolic and flavonoid contents of the extracts were determined using Folin-Ciocaltaeu's and AlCl 3 reagents, respectively. None of the extracts had any marked inhibition against tyrosinase, while they exerted a low inhibition against AChE and BChE at 200 μg/mL. The aqueous and methanol extracts displayed a strong antioxidant activity in DPPH and DMPD radical quenching tests as well as FRAP and metal-chelation capacity assays. [ABSTRACT FROM AUTHOR]

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a key enzyme involved in cholesterol biosynthesis and one of the most important targets for the treatment of hypercholesterolemia. A limited number of studies on the HMG-CoA reductase inhibitory potential of natural products are available. Thus, in the current study, we aimed to test the HMG-CoA reductase inhibitory capacity of extracts from the roots and aerial parts of Salvia multicaulis Vahl., through activity-guided isolation. Our findings revealed that the root extract prepared with dichloromethane–acetone (1:1) showed the highest inhibition (71.97 ± 0.37%) at 100 µg/mL. The extract was then initially fractionated by column chromatography and the obtained fractions were monitored by thin layer chromatography. Fractions which were similar to each other were combined and a total of 15 fractions were obtained. Further conventional chromatographic studies were carried out on the active fractions. Based on these fractions, 10 known compounds, comprising 9 terpenes and 1 steroid derivative in total, were isolated and their structures were verified by a combination of IT-TOF-MS, and 1D and 2D NMR techniques. According to the enzyme inhibition data of the identified compounds, 7-acetoxyhorminone exerted the highest inhibition (84.15 ± 0.10%, IC50 = 63.6 ± 1.21 µg/mL). The molecular docking experiments on 7-acetoxyhorminone and horminone indicated that both compounds strongly bind to the active site of the enzyme. [ABSTRACT FROM AUTHOR]

Context: Scorzonera L. species (Asteraceae) are edible and as medicinal plants are used for various purposed in folk medicine. Objective: The methanol extracts of the aerial parts and roots from 27 Scorzonera taxa were investigated for their possible neurobiological effects. Materials and methods: Inhibitory potential of the Scorzonera species was tested against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase (TYRO) at 100 µg mL−1 using ELISA microtiter assay. Antioxidant activity of the extracts was tested with radical scavenging activity, metal-chelation capacity, ferric- (FRAP), and phosphomolibdenum-reducing antioxidant power (PRAP) assays. Chlorogenic acid, hyperoside, rutin, and scorzotomentosin-4- O-β-glucoside were also screened in the same manner. Total phenol and flavonoid quantification in the extracts were determined spectrophotometrically. Results: The aerial parts of Scorzonera pisidica (40.25 ± 0.74%) and chlorogenic acid (46.97 ± 0.82%) displayed the highest TYRO inhibition, while the remaining samples showed only trivial inhibition against cholinesterases (2.08 ± 1.35%-25.32 ± 1.37%). The same extract of S. pisidica was revealed to be the most potent in scavenging of all three radicals and FRAP assay. Discussion and conclusion: Out of 27 taxa, S. pisidica, in particular, may deserve further investigation for its neuroprotective potential. [ABSTRACT FROM AUTHOR]

Highlights: [•] Peony species are used for ornamental purpose because of their attractive flowers. [•] Neuroprotective effect of the peony seed extracts was screened for the first time. [•] The extracts displayed potent inhibition against AChE and BChE and TYRO. [•] Fatty acid composition of the seed oils was also determined for the first time by GC–MS. [•] The seed oils were rich in oleic, linoleic, and linolenic acids. [ABSTRACT FROM AUTHOR]

• Annual phytochemical profile of 5 Origanum species was established. • Cholinesterase inhibition and antioxidant effects of 60 extracts were tested. • The links between the phytochemical fingerprints and activities were revealed. • Aromadendrin showed good correlation with AChE, BChE, and FRAP activities. • Caffeoylarbutin had the lowest binding energy against both enzymes. The ethanol extracts of five Origanum species : O. majorana L., O. onites L., O. syriacum L., O. vulgare subsp. hirtum (Link) Ietsw., and O. vulgare subsp. viride (Boiss.) Hayek, collected annually (each month), were investigated for their cholinesterase inhibition and antioxidant effects. The phytochemical composition of a total of 60 extracts was assessed by HPLC-DAD-ESI/HRMS, revealing the presence of a total of 73 compounds. Possible correlation between the bioactivity and metabolite profiles during 12 months was monitored. Acetylcholinesterase (AChE) inhibitory activity was found to be the highest between April and November (50.29–75.95%, 200 μg/mL), while the highest inhibition towards butyrylcholinesterase (BChE) was observed for the extracts between April and October (71.68–88.97%). Aromadendrin showed good correlation with anti-AChE, anti-BChE and reducing power activities. Furthermore, molecular docking data with aromadendrin, caffeoylarbutin and eriodictyol indicated that caffeoylarbutin had the lowest binding energy against both enzymes. [ABSTRACT FROM AUTHOR]

The dichloromethane (DCM), ethyl acetate (EtOAc), and methanol extracts from the leaves, roots, and flowers of the five species of Gentiana ( Gentiana asclepiadea, Gentiana cruciata, Gentiana olivieri, Gentiana septemfida, and Gentiana verna) and Gentianella caucasea were investigated for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and antioxidant effect using 2,2-diphenyl-1-picrylhydrazyl radical scavenging, metal-chelation capacity, and ferric-reducing antioxidant power assays. Total phenol and flavonoid contents of the extracts were determined spectrophotometrically. The presence of some characteristic compounds found in Gentiana species (gentiopicroside, swertiamarin, isoorientin, isovitexin and vitexin) was analyzed in the extracts by thin layer chromatography. The flower DCM extract of G. verna exerted the highest inhibition against AChE (53.65 ± 1.03%), whereas the root EtOAc extract of G. cruciata was the most effective in BChE inhibition assay (50.72 ± 0.75%) at 100 μg ml− 1. The extracts of G. verna were also found to be more active in the antioxidant tests. [ABSTRACT FROM AUTHOR]

The ethyl acetate and ethanol extracts obtained from eight varieties (Faikbey, Y-1779, CI-8357, Cheokota, Seydişehir, Y-330, Sivas and YVD-18) of oat (Avena sativa L.), one variety (Larende) of barley (Hordeum vulgare L.), one variety (Tatlicak 97) of triticale (Triticale sp.) and one rye variety (Aslim 95) (Secale cereale L.) were investigated for their antioxidant effects in seven test systems. Anticholinesterase activity of the extracts was examined by enzyme-linked immunosorbent assay (ELISA) microplate reader. Total phenol and flavonoid contents were calculated using Folin Ciocalteau and AlCl3 reagents, respectively. All of the extracts were ineffective in cholinesterase inhibition assays and had weak-to-moderate activity in antioxidant assays. The extracts exerted better activity in iron-chelation capacity ranging between 43.17 ±  2.04 and 62.97 ± 1.29%. Triticale extracts showed higher activity in reducing power experiments. A notable difference in the results of the antioxidant activity assays was observed among the oat varieties. [ABSTRACT FROM AUTHOR]

Abstract: In the current work, the acetone, ethyl acetate, and ethanol extracts and essential oils of the twigs and needles of five Turkish Pinus species; P. brutia, P. halepensis, P. nigra, P. pinea, and P. sylvestris along with pycnogenol (the bark extract of P. pinaster) were examined for their inhibitory effects against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at 200μgmL−1. Their antioxidant activity was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and N,N-dimethyl-p-phenylendiamine (DMPD) radical scavenging, metal-chelation, and ferric-reducing antioxidant power (FRAP) assays. Total phenol and flavonoid contents of the extracts were determined by Folin–Ciocalteau and AlCl3 reagents, respectively. GC–MS technique was applied for compositional profile of the essential oils of the tested species. Accordingly, the best AChE and BChE inhibition was caused by the twig essential oil (83.91±3.95%) and the needle ethanol extract (82.47±5.57%) of P. halepensis, respectively. Pycnogenol also caused a remarkable inhibition against AChE (63.33±0.22%) and BChE (83.67±0.22%). The extracts and essential oils usually showed a strong activity in the antioxidant assays. Pycnogenol exhibited a potent antioxidant effect and had the richest total phenol content. In the essential oils, α- and β-pinene were identified the major components. These results reveal that the Pinus species and pycnogenol are the potential sources of active metabolites with cholinesterase and antioxidant properties. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Galium species have been reported to be used against epilepsy in traditional Turkish folk medicine. Aim of study: The present work was undertaken to evaluate the in vivo anticonvulsant and in vitro neuroprotective effects of Galium spurium L. and to determine the major constituents by UPLC–TOF-MS. Materials and methods: Anticonvulsant activity of the aerial parts of Galium spurium was investigated using pentylenetetrazole, picrotoxin, and maximal electroshock-induced seizure animal models. In order to evaluate the safety, neurotoxicity (Rota rod test) of the ethanol extract was also determined. In vitro neuroprotective effect of the ethanol extract of Galium spurium was assessed by acetylcholinesterase and butrylcholinesterase inhibitions. Ultra Performance Liquid Chromatography–Time of Flight Mass Spectrometer (UPLC–TOF-MS) was used to identify the major compounds in the extract. Results: In pentylenetetrazole-induced seizure, the ethanol extract at doses of 250 and 1000mg/kg prolonged the onset of seizures. Similarly, Galium spurium (250 and 500mg/kg) significantly delayed the onset of picrotoxin-induced seizures in mice and these doses also exhibited 12.5% and 17% protection, respectively, against picrotoxin-induced seizures. Furthermore, Galium spurium extract showed a significant protective effect against maximal electroshock-induced seizures at doses of 250 and 1000mg/kg (50% and 37.5%, respectively) and also all tested doses prolonged the onset of seizures. No motor co-ordination was observed with intraperitoneal injection of Galium spurium extract at doses of 500 and 1000mg/kg. The extract exhibited 16.2% inhibition against butrylcholinesterase at 200μg/mL concentration, whereas it did not inhibit acetylcholinesterase. Phytochemical analysis of the extract based on the MS data by UPLC–TOF-MS, ten major compounds (phenolic and triterpenic acids, flavonoids and iridoids) were determined. Conclusions: The results indicate that Galium spurium may have anticonvulsant activity against picrotoxin and maximal electroshock-induced seizures in mice. Phenolic acids, flavonoids and iridoids might be responsible for anticonvulsant activity. The results offer possible beneficial effects by the plant''s aerial parts and may suggest a realistic explanation for its traditonal usage in epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Galium species have been reported to be used against epilepsy in traditional Turkish folk medicine. Aim of study: The present work was undertaken to evaluate the in vivo anticonvulsant and in vitro neuroprotective effects of Galium spurium L. and to determine the major constituents by UPLC–TOF-MS. Materials and methods: Anticonvulsant activity of the aerial parts of Galium spurium was investigated using pentylenetetrazole, picrotoxin, and maximal electroshock-induced seizure animal models. In order to evaluate the safety, neurotoxicity (Rota rod test) of the ethanol extract was also determined. In vitro neuroprotective effect of the ethanol extract of Galium spurium was assessed by acetylcholinesterase and butrylcholinesterase inhibitions. Ultra Performance Liquid Chromatography–Time of Flight Mass Spectrometer (UPLC–TOF-MS) was used to identify the major compounds in the extract. Results: In pentylenetetrazole-induced seizure, the ethanol extract at doses of 250 and 1000mg/kg prolonged the onset of seizures. Similarly, Galium spurium (250 and 500mg/kg) significantly delayed the onset of picrotoxin-induced seizures in mice and these doses also exhibited 12.5% and 17% protection, respectively, against picrotoxin-induced seizures. Furthermore, Galium spurium extract showed a significant protective effect against maximal electroshock-induced seizures at doses of 250 and 1000mg/kg (50% and 37.5%, respectively) and also all tested doses prolonged the onset of seizures. No motor co-ordination was observed with intraperitoneal injection of Galium spurium extract at doses of 500 and 1000mg/kg. The extract exhibited 16.2% inhibition against butrylcholinesterase at 200μg/mL concentration, whereas it did not inhibit acetylcholinesterase. Phytochemical analysis of the extract based on the MS data by UPLC–TOF-MS, ten major compounds (phenolic and triterpenic acids, flavonoids and iridoids) were determined. Conclusions: The results indicate that Galium spurium may have anticonvulsant activity against picrotoxin and maximal electroshock-induced seizures in mice. Phenolic acids, flavonoids and iridoids might be responsible for anticonvulsant activity. The results offer possible beneficial effects by the plant''s aerial parts and may suggest a realistic explanation for its traditonal usage in epilepsy. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological Relevance: Salvia L. species are widely used against wounds and skin infections in Turkish folk medicine. Aim of the study: The aim of the present study is to evaluate wound healing activity of the ethanol (EtOH) extracts of Salvia cryptantha and Salvia cyanescens. Materials and methods: For the assessment of wound healing activity linear incision and circular excision wound models were employed on rats and mice. The wound healing effect was comparatively evaluated with the standard skin ointment Madecassol®. Inhibition of tyrosinase, a key enzyme in skin aging, was achieved using ELISA microplate reader. Antioxidant activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical scavenger effect, ferrous ion-chelating ability, and ferric-reducing antioxidant power (FRAP) tests. Results and Conclusions: The EtOH extract of Salvia cryptantha treated groups of animals showed 56.5% contraction, whereas the reference drug Madecassol® showed 100% contraction. On the other hand, the same extract on linear incision wound model demonstrated a significant increase (33.2%) in wound tensile strength as compared to other groups. The results of histopathological examination maintained the upshot of linear incision and circular excision wound models as well. These findings specify that Salvia cryptantha for wound healing activity can be appealed further phytochemical estimation for spotting its active components. [Copyright &y& Elsevier]

Phosphodiesterases (PDEs) consisted of 11 subtypes (PDE1 to PDE11) and over 40 isoforms that regulate levels of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), the second messengers in cell functions. PDE inhibitors (PDEIs) have been attractive therapeutic targets due to their involvement in diverse medical conditions, e.g. cardiovascular diseases, autoimmune diseases, Alzheimer's disease (AD), etc. Among them; AD with a complex pathology is a progressive neurodegenerative disorder which affect mostly senile people in the world and only symptomatic treatment particularly using cholinesterase inhibitors in clinic is available at the moment for AD. Consequently, novel treatment strategies towards AD are still searched extensively. Since PDEs are broadly expressed in the brain, PDEIs are considered to modulate neurodegenerative conditions through regulating cAMP and cGMP in the brain. In this sense, several synthetic or natural molecules inhibiting various PDE subtypes such as rolipram and roflumilast (PDE4 inhibitors), vinpocetine (PDE1 inhibitor), cilostazol and milrinone (PDE3 inhibitors), sildenafil and tadalafil (PDE5 inhibitors), etc have been reported showing encouraging results for the treatment of AD. In this review, PDE superfamily will be scrutinized from the view point of structural features, isoforms, functions and pharmacology particularly attributed to PDEs as target for AD therapy. Image 1 • Phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP as well as cGMP controlling many physiological processes. • AD is one of the most prevalent age-related neurodegenerative diseases typically associated with neuroinflammation. • Pharmacological targets which are involved in blocking PDEs can be considered as new medicinal approaches in cognitive disorders and dementia. • Several neuropsychopharmacological mechanisms are involved in therapeutic effect of PDEs inhibitors in AD. • Numerous cellular signaling pathways are involved in beneficial effects of PDEs in AD such as PKA/PKG and cAMP/CREB/BDNF. [ABSTRACT FROM AUTHOR]

• Novel [3-substitue-6-oxopyridazin-1(6 H)-yl]methyl carbamate derivatives were synthesized. • Compounds 7c , 14c , and 16c showed significant inhibitory activity against eqBuChE. • Compound 7c displayed a competitive inhibition while 14c and 16c showed a mixed-type inhibition. • Molecular docking study was performed for the selected compounds. In the current study, forty-four new [3-(2/3/4-methoxyphenyl)-6-oxopyridazin-1(6 H)-yl]methyl carbamate derivatives were synthesized and evaluated for their ability to inhibit electric eel acetylcholinesterase (Ee AChE) and equine butyrylcholinesterase (eqBuChE) enzymes. According to the inhibitory activity results, [3-(2-methoxyphenyl)-6-oxopyridazin-1(6 H)-yl]methyl heptylcarbamate (16c , eqBuChE, IC 50 = 12.8 μM; Ee AChE, no inhibition at 100 μM) was the most potent eqBuChE inhibitor among the synthesized compounds and was found to be a moderate inhibitor compared to donepezil (eqBuChE, IC 50 = 3.25 μM; Ee AChE, IC 50 = 0.11 μM). Kinetic and molecular docking studies indicated that compounds 16c and 14c (hexylcarbamate derivative, eqBuChE, IC 50 = 35 μM; Ee AChE, no inhibition at 100 μM) were mixed-type inhibitors which accommodated within the catalytic active site (CAS) and peripheral anionic site (PAS) of hBuChE through stable hydrogen bonding and π-π stacking. Furthermore, it was determined that [3-(2-methoxyphenyl)-6-oxopyridazin-1(6 H)-yl]methyl (4-methylphenyl)carbamate 7c (eqBuChE, IC 50 = 34.5 μM; Ee AChE, 38.9% inhibition at 100 μM) was the most active derivative against Ee AChE and a competitive inhibitor binding to the CAS of hBuChE. As a result, 6-(2-methoxyphenyl)pyridazin-3(2 H)-one scaffold is important for the inhibitory activity and compounds 7c , 14c and 16c might be considered as promising lead candidates for the design and development of selective BuChE inhibitors for Alzheimer's disease treatment. [ABSTRACT FROM AUTHOR]

Chrysin is a promising phytochemical that is categorized under the class of flavonoids based on its chemical structure. Naturally, it is widely present in propolis, honey, passion fruit, and even in mushrooms and other plant sources, whereas its synthetic counterparts are also being employed for pharmacological purposes. It has widely been employed in treatment of various degenerative disorders and provides cytotoxic and anti-inflammatory functions. Its antioxidant and disease preventing abilities are attributed to its structural diversity arising in ring-A and absence of oxygenation in B and C ring. In this review, the scientific studies are being reported emphasizing benefits and its allied health claims on chrysin in numerous metabolic malfunctions. Graphical abstract of chrysin sources and its health claims Unlabelled Image [ABSTRACT FROM AUTHOR]