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Biological activities of six under-utilized medicinal leafy vegetable plants indigenous to Africa, i.e., Basella alba, Crassocephalum rubens, Gnetum africanum, Launaea taraxacifolia, Solanecio biafrae, and Solanum macrocarpon, were investigated via two independent techniques. The total phenolic content (TPC) was determined, and six microtiter plate assays were applied after extraction and fractionation. Three were antioxidant in vitro assays, i.e., ferric reducing antioxidant power (FRAP), cupric reduction antioxidant capacity (CUPRAC), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, and the others were enzyme (acetylcholinesterase, butyrylcholinesterase, and tyrosinase) inhibition assays. The highest TPC and antioxidant activity from all the methods were obtained from polar and medium polar fractions of C. rubens, S. biafrae, and S. macrocarpon. The highest acetyl- and butyrylcholinesterase inhibition was exhibited by polar fractions of S. biafrae, C. rubens, and L. taraxacifolia, the latter comparable to galantamine. The highest tyrosinase inhibition was observed in the n-butanol fraction of C. rubens and ethyl acetate fraction of S. biafrae. In vitro assay results of the different extracts and fractions were mostly in agreement with the bioactivity profiling via high-performance thin-layer chromatography–multi-imaging–effect-directed analysis, exploiting nine different planar assays. Several separated compounds of the plant extracts showed antioxidant, α-glucosidase, α-amylase, acetyl- and butyrylcholinesterase-inhibiting, Gram-positive/-negative antimicrobial, cytotoxic, and genotoxic activities. A prominent apolar bioactive compound zone was tentatively assigned to fatty acids, in particular linolenic acid, via electrospray ionization high-resolution mass spectrometry. The detected antioxidant, antimicrobial, antidiabetic, anticholinesterase, cytotoxic, and genotoxic potentials of these vegetable plants, in particular C. rubens, S. biafrae, and S. macrocarpon, may validate some of their ethnomedicinal uses. [ABSTRACT FROM AUTHOR]

• Insecticidal activity of 47 macroalgae mostly from Mediterranean Sea was examined. • Cholinesterase and tyrosinase inhibitory effect of the alga extracts was investigated. • D. dichotoma var. intricata was the only one exhibiting BChE inhibition over 50%. • BChE inhibition by four diterpenes in DDI was investigated in silico. • The macroalgae and their metabolites might be new sources of novel insecticides. Ethanolic extracts prepared from forty-seven macroalgae species collected from the Mediterranean Sea, Aegean Sea, and Sea of Marmara were tested at 200 μg/mL against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase (TYR), crucial for insect vivacity. Only one alga extract, e.g. Dictyota dichotoma var. intricata (C.Agardh) Greville 1830, had a notable inhibition of BChE (72.0 ± 0.07%), whereas the rest of the macroalgae possessed no or low inhibition of AChE (2.20 ± 0.39% - 14.20 ± 2.16%), BChE (0.62 ± 0.07% - 41.20 ± 3.07%), and TYR (< 10%). Several known diterpenes (isoamijiol, 14-deoxyamijiol, amijidictyol, dictyodial, and 4α-acetoxydictyodial) found earlier in this species were proceeded to molecular docking experiments to figure out its interactions with BChE. Eleven of the 47 macroalgal extracts were selected based on sufficient availability for testing in larvicidal and adulticidal activity assays against female Aedes aegypti "Orlando1952" the mosquito vector of yellow fever and dengue. The selected extracts displayed a high adulticidal activity ranging between 80–100% activity at 5 μg/mosquito. In contrast, only the ethanol extract of Ceramium siliquosum var. elegans showed larvicidal mortality of 93.3 ± 11.5% at 0.5 μg/mL. Our findings show that the macroalgae and their metabolites could be sources of novel insecticidal agents. [ABSTRACT FROM AUTHOR]

• Isoquinoline alkaloids were tested against cholinesterases in vitro and in silico. • N -norgalanthamine is the most active one inhibiting both cholinesterases. • 8-Hydroxy-9-methoxycrinine was a strong inhibitor of AChE. • (+)-9- O -demethylhomolycorine displayed a moderate BChE inhibition. • This is the first report on ChE inhibition by three off the tested alkaloids. All cholinesterase (ChE) inhibitory drugs in clinical use are nitrogenous compounds and among them, galanthamine as the latest anticholinesterase drug, contains a tetrahydroisoquinoline structure. For this reason, isoquinoline alkaloids seem to be attractive in search for novel drug candidates towards Alzheimer's disease (AD). Therefore, in the current work, we investigated inhibitory capacity of several alkaloids representing expanding group of biogenetically-related isoquinoline alkaloids from the Amaryllidaceae including lycorine, (+)-9- O -demethylhomolycorine, 6-hydroxybuphanisine, 9- O -demethoxymontanine, 3- epi- hydroxy-bulbispermine, tazettine, haemanthamine, (+)-haemanthidine, (-)-crinine, 8-hydroxy-9-methoxycrinine, and N -norgalanthamine against ChEs by microtiter enzyme inhibition assays. Our findings indicated that N -norgalanthamine is the most active one inhibiting both acetylcholinesterase (AChE, IC 50 = 2.42 ± 0.16 µg/mL) and butyrylcholinesterase (BChE, IC 50 = 20.87 ± 1.01 µg/mL) at 100 μg/mL, whereas IC 50 values of galanthamine used as the reference were 1.33 ± 0.11 µg/mL and 37.69 ± 2.93 µg/mL for AChE and BChE, respectively. Beside this, 8-hydroxy-9-methoxycrinine was a strong inhibitor of AChE (IC 50 = 6.92 ± 0.51 µg/mL), while (+)-9- O -demethylhomolycorine displayed a moderate BChE inhibition (IC 50 = 83.57 ± 1.36 µg/mL). Relevantly, 8-hydroxy-9-methoxycrinine and N -norgalanthamine were docked into active gorges of hAChE (PDB: 4EY6) and hBChE (PDB: 4TPK), which pointed out the detail that N -norgalanthamine displayed a very similar binding mode of to that of galanthamine. Moreover, both AChE-inhibiting alkaloids were found to stably bind to hAChE active site occupying the middle of the gorge between the catalytic site and the peripheral anionic site. 8-Hydroxy-9-methoxycrinine was also docked into the active site of BChE. We can conclude that among the tested alkaloids, N -norgalanthamine with dual ChE inhibitory effect seems to be the most promising anti-Alzheimer candidate molecule for future experiments. [ABSTRACT FROM AUTHOR]

COVID-19 caused by a new type of coronavirus (SARS-CoV-2) originated in China has speedily become a frightening pandemic all over the world. Despite of intense efforts relevant to experimental and clinical studies since the start of the COVID-19 pandemic, no disease-specific drug or vaccine is available, yet. Several treatment strategies including already known antiviral drugs, interpherons, interleukin inhibitors, and other drugs acting through different mechanims are being implemented in COVID-19 patients. On the other hand, natural products especially pythocompounds have been proven to be lead molecules for drug design and development research. Among them, curcumin as the main constituent of Curcuma longa L. (turmeric), is the reputed compound displaying remarkable biological activities for human health. It has been shown to have a inhibiting effect against a wide range of viruses such as HCV, HIV, PEDV, HSV, Ebola, dengue, influenza, Zika, SARS-CoV, etc. Therefore, curcumin could be considered as a structural model for designing new molecules against COVID-19. In the present review, antiviral activity of curcumin is scrutinized thorugh the literature data relevant to its enzyme and receptor interactions, in vitro, in vivo, in silico, and cell-based assays. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • 26 O-alkylcoumarins were synthesized and tested at 100 µM for their in vitro inhibitory potential against cholinesterases. • 12 of them exerted a potent and selective inhibition against BChE. • None of them possessed any potential to inhibit AChE. • MetaCore/MetaDrug analysis and docking simulations were applied the active compounds. Abstract Coumarins of synthetic or natural origins are an important chemical class exerting diverse pharmacological activities. In the present study, 26 novel O-alkylcoumarin derivatives were synthesized and have been tested at 100 µM for their in vitro inhibitory potential against acetylcholinesterase (AChE) and butyrlcholinesterase (BChE) targets which are the key enzymes playing role in the pathogenesis of Alzheimer's disease. Among the tested coumarins, none of them could inhibit AChE, whereas 12 of them exerted a marked and selective inhibition against BChE as compared to the reference (galanthamine, IC 50 = 46.58 ± 0.91 µM). In fact, 10 of the active coumarins showed higher inhibition (IC 50 = 7.01 ± 0.28 µM – 43.31 ± 3.63 µM) than that of galanthamine. The most active ones were revealed to be 7-styryloxycoumarin (IC 50 = 7.01 ± 0.28 µM) and 7-isopentenyloxy-4-methylcoumarin (IC 50 = 8.18 ± 0.74 µM). In addition to the in vitro tests, MetaCore/MetaDrug binary QSAR models and docking simulations were applied to evaluate the active compounds by ligand-based and target-driven approaches. The predicted pharmacokinetic profiles of the compounds suggested that the compounds reveal lipophilic character and permeate blood brain barrier (BBB) and the ADME models predict higher human serum protein binding percentages (>50%) for the compounds. The calculated docking scores indicated that the coumarins showing remarkable BChE inhibition possessed favorable free binding energies in interacting with the ligand-binding domain of the target. Therefore, our results disclose that O-alkylcoumarins are promising selective inhibitors of cholinesterase enzymes, particularly BChE in our case, which definitely deserve further studies. [ABSTRACT FROM AUTHOR]

Pteryxin is a dihydropyranocoumarin derivative found in Apiaceae family. In this study, pteryxin, which was previously isolated from the fruits of Mutellina purpurea , was investigated for its inhibitory potential against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are the key enzymes in the pathology of Alzheimer's disease (AD). The compound was tested in vitro using ELISA microplate reader at 100 μg/ml and found to cause 9.30 ± 1.86% and 91.62 ± 1.53% inhibition against AChE and BChE, respectively. According to our results, pteryxin (IC 50 = 12.96 ± 0.70 μg/ml) was found to be a more active inhibitor of BChE than galanthamine (IC 50 = 22.16 ± 0.91 μg/ml; 81.93± 2.52% of inhibition at 100 μg/ml). Further study on pteryxin using molecular docking experiments revealed different possible binding modes with both polar and hydrophobic interactions inside the binding pocket of BChE. Top docking solution points out to the formation of two hydrogen bonds with the catalytic residues S198 and H438 of BChE as well as a strong π - π stacking with W231. Therefore, pteryxin as a natural coumarin seems to be a strong BChE inhibitor, which could be considered as a lead compound to develop novel BChE inhibitors for AD treatment. [ABSTRACT FROM AUTHOR]

The article discusses a study which assessed the antioxidant potential of various extracts obtained from the leaf and fruit of Maclura pomifera, Schneider and its major isoflavonoids. Topics covered include findings which show the antioxidant capacity of iso-osajin, iso-pomiferin, and macluraxanthone, and indications that pomiferin is a natural possible antioxidant agent.

The neurobiological activity of the methanol extracts of thirteen Umbelliferae (Apiaceae) plants was tested against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase (TYR) using a high-throughput screening technique. Although the extracts displayed no to a low inhibition profile against the enzymes, the highest cholinesterase inhibition was observed with Heracleum platytaenium (32.52±3.27 % for AChE and 46.16±1.42 % for BChE) at 100 μg mL-1. Since neurodegeneration is linked to oxidative damage, the antioxidant potential of the extracts were examined through radical scavenging, metal-chelating capacity, and reducing power experiments and they exerted modest levels of activity varying according to the method. The extracts had a better ability to scavenge the nitric oxide radical (19.47±2.09 to 54.91±1.98 %). Since these species are known to be rich in coumarins, quantitative high-performance liquid chromatography (HPLC) analysis indicated the presence of xanthotoxin, angelicin, isopimpinellin, bergapten, and pimpinellin in Heracleum platytaenium and angelicin and imperatorin in Angelica sylvestris var. sylvestris. [ABSTRACT FROM AUTHOR]

The extracts from 25 plant species from Salvia , Hypericum , Onosma , Thymus , Origanum , Rosa , and Prunus with eight isolated compounds were screened for their memory-vitalizing potential against the enzymes, i.e., acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase (TYR) along with DPPH, DMPD, and NO radicals and iron-chelation capacity using spectrophotometric microtiter assays. The n -hexane:dichloromethane (1:1) extract of Onosma nigricaule roots (63.18 ± 0.56%) and the ethyl acetate extract of the aerial parts of Hypericum capitatum var. capitatum (50.79 ± 3.88%) were the most active toward AChE and BChE, respectively. The highest iron-chelating capacity was found in the n -hexane extract of Thymus sipyleus subsp. sipyleus var. sipyleus , where mostly Labiatae species exhibited better radical scavenging effect. Among the extracts, the roots of O. nigricaule , the aerial parts of Hypericum capitatum var. capitatum and T . sipyleus subsp. sipyleus var. sipyleus could be further evaluated for their memory-vitalizing properties based on different mechanisms. [ABSTRACT FROM AUTHOR]

Hypericum perforatum L. (St. John's Wort) is a reputed plant with a long service to humankind. In the current study, antioxidant activity of the methanol extract of the aerial parts of H. perforatum growing in Turkey along with hyperoside and hyperforin was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, metal-chelation, and ferric-reducing antioxidant power (FRAP) assays. The major components including chlorogenic acid, the flavonoid derivatives; rutin, hyperoside, quercitrin, quercetin, and biapigenin, the naphthodianthrons; pseudohypericin and hypericin, and the phloroglucinol derivatives; hyperforin and adhyperforin were quantified in the extract by LC-DAD-MS. Hypericin (16 ± 0.08 μg/g) and hiperforin (1164 ± 0.02 μg/g) contents in H. perforatum were found to be in accordance with the amounts required by the European Pharmacopeia. The extract and hyperoside exerted a remarkable antioxidant activity in DPPH radical scavenging and FRAP assays, whereas they did not have metal-chelation capacity. [ABSTRACT FROM AUTHOR]

Ethnopharmacology has been an important starting point in medical and pharmaceutical sciences for discovering drug candidates from natural sources. In this regard, the genus Salvia L., commonly known as sage, is one of the best-known medicinal and aromatic plants of the Lamiaceae family; it has been recorded as being used for memory enhancement in European folk medicine. Despite the various uses of sage in folk medicines, the records that have pointed out sage's memory-enhancing properties have paved the way for the aforementioned effect to be proven on scientific grounds. There are many preclinical studies and excellent reviews referring to the favorable effect of different species of sage against the cognitive dysfunction that is related to Alzheimer's disease (AD). Hence, the current review discusses clinical studies that provide evidence for the effect of Salvia species on cognitive dysfunction. Clinical studies have shown that some Salvia species, i.e., hydroalcoholic extracts and essential oils of S. officinalis L. and S. lavandulaefolia leaves in particular, have been the most prominently effective species in patients with mild to moderate AD, and these species have shown positive effects on the memory of young and healthy people. However, the numbers of subjects in the studies were small, and standardized extracts were not used for the most part. Our review points out to the need for longer-term clinical studies with higher numbers of subjects being administered standardized sage preparations. [ABSTRACT FROM AUTHOR]

The extracts of various marine sponges (Agelas oroides and Axinella damicornis, Axinella cannabina, Ircinia spinulosa, I. fasciculata, and I. variabilis, Dysidea avara, and Sarcotragus spinulosus) collected from different spots of the Turkish cost of the Mediterranean Sea have been evaluated for their antibacterial, antifungal, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, and acetylcholinesterase (AChE) inhibitory activities. Three compounds (oroidin, 4,5-dibromopyrrol-2-carboxylic acid, and 25-hydroxy-24-methylcholesterol) were isolated from A. oroides and tested in the same manner. The sponge extracts showed notable antimicrobial and anti-AChE activity and low DPPH scavenging activity. Oroidin was found to have moderate anti-AChE and strong radical scavenging activities. The results demonstrated that the sponge extracts exerted a variable degree of antibacterial, anti-radical, and anti-AChE activity, whereas they seemed to have similar antifungal effect. Our findings point out to the fact that the collection site has an important influence on bioactivity of the sponges. [ABSTRACT FROM AUTHOR]

This paper covers the studies relevant to neuroprotective activity of Centella asiatica (L.) Urban, also known as "Gotu Kola." The plant is native to the Southeast Asia and has been used traditionally as brain tonic in ayurvedic medicine. The neuroprotective effect of C. asiatica has been searched using the key words "Centella, Centella asiatica, gotu kola, Asiatic pennywort, neuroprotection, and memory" through the electronic databases including Sciencedirect, Web of Science, Scopus, Pubmed, and Google Scholar. According to the literature survey, C. asiatica (gotu kola) has been reported to have a comprehensive neuroprotection by different modes of action such as enzyme inhibition, prevention of amyloid plaque formation in Alzheimer's disease, dopamine neurotoxicity in Parkinson's disease, and decreasing oxidative stress. Therefore, C. asiatica could be suggested to be a desired phytopharmaceutical with neuroprotective effect emerged from traditional medicine. [ABSTRACT FROM AUTHOR]

Abstract: In vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory and antioxidant activities of the aqueous and ethanol extracts of the leaves, ripe fruits, and unripe fruits of Juniperus communis ssp. nana, Juniperus oxycedrus ssp. oxycedrus, Juniperus sabina, Juniperus foetidissima, and Juniperus excelsa were investigated in the present study. Cholinesterase inhibition of the extracts was screened using ELISA microplate reader. Antioxidant activity of the extracts was tested by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical scavenging, ferrous ion-chelating, and ferric-reducing antioxidant power (FRAP) assays. Total phenol and flavonoid contents of the extracts were determined spectrophotometrically. The extracts had low or no inhibition towards AChE, whereas the leaf aqueous extract of J. foetidissima showed the highest BChE inhibition (93.94±0.01%). The leaf extracts usually exerted higher antioxidant activity. We herein describe the first study on anticholinesterase and antioxidant activity by the methods of ferrous ion-chelating, superoxide radical scavenging, and ferric-reducing antioxidant power (FRAP) assays of the mentioned Juniperus species. [Copyright &y& Elsevier]

In the current study, we examined anti-acetylcholinesterase (AChE) and antioxidant activities of the ethyl acetate, methanol, and water extracts from the bulbs of Turkish Sternbergia Waldst. & Kit. (Amaryllidaceae) species; S. candida, S. clusiana, S. fisheriana, S. lutea subsp. lutea, and S. lutea subsp. sicula. Anti-AChE activity was tested by spectrophotometric method of Ellman using ELISA microplate reader at 50, 100, and 200 µg mL-1 concentrations. Antioxidant activity of the extracts was evaluated by DPPH radical scavenging activity, ferrous ion-chelating capacity, ferric-reducing antioxidant power, and beta-carotene bleaching assays at 500, 1000, and 2000 µg mL-1. Total phenol and flavonoid contents of the extracts were determined via Folin-Ciocalteau's and AlCl3 reagents, respectively. The ethyl acetate extract of S. fischeriana was the most active in anti-AChE assay (90.94% and 98.02% of inhibitions at 100 and 200 µg mL-1 concentrations, respectively. Antioxidant activity of the extracts was found to be not significant. [ABSTRACT FROM AUTHOR]

Pharmacognosy deals with the natural drugs obtained from organisms such as most plants, microbes, and animals. Up to date, many important drugs including morphine, atropine, galanthamine, etc. have originated from natural sources which continue to be good model molecules in drug discovery. Traditional medicine is also a part of pharmacognosy and most of the third world countries still depend on the use of herbal medicines. Consequently, pharmacognosy always keeps its popularity in pharmaceutical sciences and plays a critical role in drug discovery. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the authors discuss several reports in the issue on topics including neurological activity of traditional Chinese medicine against diabetic peripheral neuropathy, neuroprotective effect of a Chinese medicine, and spinal cord injuries.

The popularity of herbal medicines and dietary supplements is increasing all over the world due to the many side-effects assigned to synthetic drugs. Herbal remedies should be considered as safe, with no side-effects, but unfortunately, even if they are labelled as natural, large numbers of adulterants, not only with toxic heavy metals but also with undeclared synthetic substances, have been detected up to date. In this review, the most frequent instances of adulteration of herbal medicines and dietary supplements acting as sexual enhancers and slimming products are thoroughly discussed. The great success of synthetic phosphodiesterase type-5 (PDE-5) inhibitory drugs like sildenafil, vardenafil and tadalafil, used for the treatment of erectile dysfunction has made them, as well as their unapproved analogues, popular as adulterants in herbal dietary supplements. The second group among blockbuster products are herbal preparations for slimming purpose, as obesity and gaining weight are major problems worldwide. Here, sibutramine hydrochloride monohydrate, an anti-obesity drug which inhibits serotonergic and noradrenergic reuptake, seems to be the most common adulterant. Together with large numbers of its analogues, thyroid hormones, anorexigens, diuretics, stimulants, and laxative agents are also detected in most of tested diet supplements. [ABSTRACT FROM AUTHOR]

Based on our continuous effort to investigate chemistry and biology of the plant secondary metabolites, we were able to isolate a glycosidal flavonoid 1 from the Wild Egyptian Artichoke. The activity of dihydromyricetin 3-O-rhamnoside (sin. dihydromyricitrin, ampelopsin 3-O-rhamnoside) (1) against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE); its absolute configuration using X-ray crystallography were determined for the first time. Inhibitory activity of 1 against AChE and BChE enzymes were determined using a slightly modified version of Ellman's method. Compound 1 was revealed to have a potent inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 0.070 ± 0.008 and 0.071 ± 0.004 mM, respectively, where IC50 values of the reference drug (galanthamine) were 0.023 ± 0.15 and 0.047 ± 0.91 mM. Compound 1 could be a promising molecule against Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Medicinal and edible plants play a crucial role in the prevention and/or mitigation of different human diseases from ancient times to today. In folk medicine, there are different plants used for infectious disease treatment. During the past two decades, much attention has been paid to plants as novel alternative therapeutic agents for the treatment of infectious diseases due to their bioactive natural compounds such as phenol, flavonoids, tannins, etc. The genus Eryngium (Apiaceae) contains more than 250 flowering plant species, which are commonly used as edible and medicinal plants in different countries. In fact, some genus Eryngium species are used as spices and are cultivated throughout the world and others species are used for the treatment of hypertension, gastrointestinal problems, asthma, burns, fevers, diarrhea, malaria, etc. Phytochemical analysis has shown that genus Eryngium species are a rich source of flavonoids, tannins, saponins, and triterpenoids. Moreover, eryngial, one the most important and major compounds of genus Eryngium plant essential oil, possesses a significant antibacterial effect. Thus, the objective of this review is to critically review the scientific literature on the phytochemical composition and antibacterial effects of the genus Eryngium plants. In addition, we provide some information about traditional uses, cultivation, as well as phytochemistry. [ABSTRACT FROM AUTHOR]

Phenylethanoid glycosides are naturally occurring water-soluble compounds with remarkable biological properties that are widely distributed in the plant kingdom. Verbascoside is a phenylethanoid glycoside that was first isolated from mullein but is also found in several other plant species. It has also been produced by in vitro plant culture systems, including genetically transformed roots (so-called ‘hairy roots’). Verbascoside is hydrophilic in nature and possesses pharmacologically beneficial activities for human health, including antioxidant, anti-inflammatory and antineoplastic properties in addition to numerous wound-healing and neuroprotective properties. Recent advances with regard to the distribution, (bio)synthesis and bioproduction of verbascoside are summarised in this review. We also discuss its prominent pharmacological properties and outline future perspectives for its potential application. [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]

• 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]

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]

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]

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]

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]

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]