BACKGROUND:Cholinesterase (ChE) inhibitors used currently in clinics for the treatment of Alzheimer's disease (AD) are the most prescribed drug class with nitrogen-containing chemical formula. Galanthamine, the latest generation anti-ChE drug, contains an isoquinoline structure.OBJECTIVE:The aim of the current study was to investigate the inhibitory potential of thirty-four isoquinoline alkaloids, e.g. (-)-adlumidine, β-allocryptopine, berberine, (+)-bicuculline, (-)-bicuculline, (+)-bulbocapnine, (-)-canadine, (±)-chelidimerine, corydaldine, (±)-corydalidzine, (-)-corydalmine, (+)-cularicine, dehydrocavidine, (+)-fumariline, (-)-fumarophycine, (+)-α-hydrastine, (+)-isoboldine, 13-methylcolumbamine, (-)-norjuziphine, norsanguinarine, (-)-ophiocarpine, (-)-ophiocarpine-Noxide, oxocularine, oxosarcocapnine, palmatine, (+)-parfumine, protopine, (+)-reticuline, sanguinarine, (+)-scoulerine, (±)-sibiricine, (±)-sibiricine acetate, (-)-sinactine, and (-)-stylopine isolated from several Fumaria (fumitory) and Corydalis species towards acetyl- (AChE) and butyrylcholinesterase (BChE) by microtiter plate assays. The alkaloids with strong ChE inhibition were proceeded to molecular docking simulations as well as in silico toxicity screening for their mutagenic capacity through VEGA QSAR (AMES test) consensus model and VEGA platform as statistical approaches. The inputs were evaluated in a simplified molecular input-line entry system (SMILES).METHODS:ChE inhibition assays indicated that the highest AChE inhibition was caused by berberine (IC50: 0.72 ± 0.04 μg/mL), palmatine (IC50: 6.29 ± 0.61 μg/mL), β-allocryptopine (IC50: 10.62 ± 0.45 μg/mL), (-)-sinactine (IC50: 11.94 ± 0.44 μg/mL), and dehydrocavidine (IC50: 15.01 ± 1.87 μg/mL) as compared to that of galanthamine (IC50: 0.74 ± 0.01 μg/mL), the reference drug with isoquinoline skeleton. Less number of the tested alkaloids exhibited notable BChE inhibition. Among them, berberine (IC50: 7.67 ± 0.36 μg/mL) and (-)-corydalmine (IC50: 7.78 ± 0.38 μg/mL) displayed a stronger inhibition than that of galanthamine (IC50: 12.02 ± 0.25 μg/mL). The mutagenic activity was shown for β-allocryptopine, (+)- and (-)-bicuculline, (±)-corydalidzine, (-)-corydalmine, (+)-cularicine, (-)- fumarophycine, (-)-norjuziphine, (-)-ophiocarpine-N-oxide, (+)-scoulerine, (-)-sinactine, and (-)- stylopine by means of in silico experiments.RESULTS:The results obtained by molecular docking simulations of berberine, palmatine, and (-)- corydalmine suggested that the estimated free ligand-binding energies of these compounds inside the binding domains of their targets are reasonable to make them capable of establishing strong polar and nonpolar bonds with the atoms of the active site amino acids.CONCLUSION:Our findings revealed that berberine, palmatin, and (-)-corydalmine stand out as the most promising isoquinoline alkaloids in terms of ChE inhibition. Among them, berberine has displayed a robust dual inhibition against both ChEs and could be evaluated further as a lead compound for AD.

Foods as medicine have been utilized from ancient civilizations and shared from generation to generation as dietary health practices. It provides therapeutic assistance along with nutrition and health benefits. Presently, food products, diet, and individual health are receiving a lot of attention and are in high demand. In this context, jaggery is an important part of food and diet in the rural areas of many regions/countries. It is made up of sugarcane juice and is recognized as a natural source of nutraceuticals due to the presence of different types of essential amino acids, minerals, vitamins, and antioxidant potential along with other biological applications. In this updated review article, we discussed the newest research and information on traditional uses, nutraceutical profiling, chemical composition, and biological applications of jaggery. The published data were collected from different scientific search engines including PubMed, Springer Link, Web of Science, Google Scholar, Science Direct, and Wiley online library. Given these findings, we can conclude that jaggery is a strong source of nutraceuticals and its nutraceutical potential can be enhanced with value addition and other scientific interventions. Detailed investigations on preclinical (in silico, in vitro , and in vivo ) studies along with its actual mechanism of action in depth are required. Additionally, clinical trials also should be conducted to validate the preclinical studies.

A new sesquiterpene (Prosoterpene, 1) and eleven reported compounds (2–12) of several classes, such as flavonoids, alkaloids, phenolic acids, and long-chain alcohols, were isolated from the BuOH extract of Prosopis africana (Guill. & Perr.) Taub. Compounds 2–10 were reported for the first time from this plant. Isomers 11 and 12 were separated for the first time. Extensive spectroscopic techniques and literature comparisons were used to characterise their structures. Furthermore, compounds 3, 5–8, and 10–12 were performed for anti-glycation and cytotoxicity activities. Compound 3 (quercetin-3-O-α-L-rhamnoside) exhibited moderate anti-glycation activity. All tested compounds were non-cytotoxic against MCF-7 (breast cancer), NCI-H460 (lung cancer), Hela (cervical cancer), and BJ (normal human fibroblast) cell lines.

COVID-19, or SARS-CoV-2, is an extremely deadly virus that is responsible for over half a million deaths of people in the world. This virus originated in China in December 2019 and rapidly spread worldwide in 2-3 months, and affected every part of the world. Its life-threatening nature forced governments in all countries to take emergency steps of lockdown that affected the entire world's education, health, social and economic aspects. Due to the implementation of these emergencies, the population is facing psychological, social and financial problems. Additionally, this pandemic has significantly influenced the health care systems as all the resources from governments of all countries were directed to invest funds to discover new diagnostic tests and manage COVID-19 infection. The impact of the COVID-19 pandemic on the education and social life of the population is described in this article. Additionally, the diagnosis, management, and phytoremediation to control the spread of COVID-19 and traditional medicinal plants' role in managing its mild symptoms have been discussed.

Urtica dioica belongs to the Urticaceae family and is found in many countries around the world. This plant contains a broad range of phytochemicals, such as phenolic compounds, sterols, fatty acids, alkaloids, terpenoids, flavonoids, and lignans, that have been widely reported for their excellent pharmacological activities, including antiviral, antimicrobial, antihelmintic, anticancer, nephroprotective, hepatoprotective, cardioprotective, antiarthritis, antidiabetic, antiendometriosis, antioxidant, anti-inflammatory, and antiaging effects. In this regard, this review highlights fresh insight into the medicinal use, chemical composition, pharmacological properties, and safety profile of U. dioica to guide future works to thoroughly estimate their clinical value.

Many therapeutic strategies are developed for the major health problems and the key enzyme inhibitory theory is one of the most applied approaches. One of the aspects of the drug discovery process is the identification of small molecules secondary metabolites with enzyme-inhibiting activities. Enzymes play an important role in all aspects of health in life and their overexpression and hypoactivation is involved in the pathogenesis of various diseases. A wide variety of therapeutics used against a number of diseases are inhibitors of clinically relevant enzymes. Most of the inhibitors interact with particular enzymes by blocking their activity towards their corresponding physiological natural substances without disturbing other enzymes. For instance, anti-acetylcholinesterase (AChE) compounds are potential candidates for treating Alzheimer's Disease (AD). Purified human enzymes are necessary as molecular targets for drug discovery. In this procedure, measurement of product formation is realized by spectroscopic methods and the results are compared by using standard clinically used inhibitors. During the past years, new enzyme inhibiting natural products from medicinally important plants have discovered. This chapter includes the general information about new inhibitors from traditionally used of medicinal plants as well as strategies to purify health related enzyme inhibitors from traditionally used medicinally important plants.

Introduction: Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol obtained from diverse groups of plants, especially in the muscadine grape, red wine, lingonberry, cranberry and redcurrant. Resveratrol's health benefits were first highlighted in the study of the French paradox, which opened up an expansive research endeavor into this compound. Ever since, an array of pharmacological activities, including antioxidant, anti-aging, anti-inflammatory, anti-cancer and antidiabetic have been attributed to resveratrol. For many poly-phenols, low solubility in biological fluids, as well as by rapid in vivo metabolization, limits their bioavailability. However, improving resveratrol formulation could enhance oral bioavailability and have other beneficial properties. The development of innovative methodological approaches, such as the utilization of innovative formulations has been developed to overcome these limitations and provide a considerable therapeutic amount of resveratrol.Results: In this narrative review, a brief outline of historical perspectives of resveratrol is provided, together with an extensive and inclusive overview of various approaches and contemporary developments on the bioavail-ability, pharmacodynamics and pharmacokinetics of this nutraceutical, along with its biotechnological appli-cations and drug formulations.

Traditional medicines can serve as the source of potential new drug candidates and initial research focuses on the isolation of bioactive lead compounds. Medicinal plants have a combination of secondary metabolites that are naturally occurred by giving different therapeutic benefits. Phytoconstituents have been recognized as an important role in the drug discovery process moreover the other sources. Presently, over hundred natural product-derived pharmaceuticals are being used in modern medicine. Plants and their secondary metabolites, with activity against targets associated with the viral infections could provide valuable leads for the development into drugs for the novel antiviral drugs. Some of them play as important tools in the immune system exhibiting antiviral potentials. The objective of this review is to conduct information regarding the potential of traditional medicines to which have shown antiviral activity against SARS-CoV-2 infection.

The aim of the present study is to determine the in vitro cholinesterase inhibitory effects of the tubers of Corydalis DC. species growing in Turkey belonging to Papaveraceae family. This genus comprises of approximately 470 species distributed in the world and is represented 17 species and 22 taxons, 8 of which are endemic, in the flora of Turkey. Some Corydalis species are used in folk medicine for the memory enhancement in Europe and China. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of the ethanolic extracts prepared from tubers collected from 54 populations are screened by the slightly modified spectrophotometric method. The highest anticholinesterase compound/s were determined by assay-guided fractionation and their structures were elucidated through chromatographic (LC-Q-ToF-MS) and extensive spectroscopic techniques. According to the results, canadine, berberine and dehydrocorydaline from protoberberine-type isoquinoline alkaloids were exerted the most potent inhibitory effect against two enzymes. This is the first study determining anticholinesterase compounds of Corydalis species growing in Turkey.

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.

The Withania genus comes from the Solanaceae family and includes around 23 species, spread over some areas of the Mediterranean, Asia, and East Africa. Widely used in traditional medicine for thousands of years, these plants are rich in secondary metabolites, with special emphasis on steroidal lactones, named withanolides which are used as ingredients in numerous formulations for a plethora of diseases, such as asthma, diabetes, arthritis, impotence, amnesia, hypertension, anxiety, stress, cancer, neurodegenerative, and cardiovascular diseases, and many others. Among them, Withania somnifera (L.) Dunal is the most widely addressed species from a pharmacological and agroindustrial point of view. In this sense, this review provides an overview of the folk uses, phytochemical composition, and biological activity, such as antioxidant, antimicrobial, anti-inflammatory, and cytotoxic activity of W. somnifera, although more recently other species have also been increasingly investigated. In addition, their health-promoting effects, i.e., antistress, anxiolytic, adaptogenic, antirheumatoid arthritis, chemoprotective, and cardiorespiratory-enhancing abilities, along with safety and adverse effects are also discussed.

The continuing research for the determination of bioactive secondary metabolites from Turkish geophytes as therapeutic agents for dementia is mainly based on the need for drug candidates affected to brain areas. In this study, the in vitro anticholinesterase activity of the alkaloidal fractions of the tubers of Corydalis triternata Zucc. was investigated for their neuroprotective potential. Furthermore, the content of the active alkaloid fractions of the tubers was determined by LC-Q-TOF-MS. The tubers of Corydalis triternata Zucc. were collected from Hatay province of Turkey. The plant species were also preserved as ex-situ in Yalova-Turkey. The alkaloidal extract was prepared from the tubers. The anticholinesterase activities of the extracts and fractions were tested by modification of the Ellman’s method. The optimization of LC-MS conditions was used in ESI in the positive ion mode. The in vitro tests were highlighted that the alkaloidal extract of the tubers exhibited the highest activity against AChE and BuChE with IC50 values of 17.56 and#177; 1.0 g/mL and 326.23 and#177; 2.6 g /mL (galanthamine 6.8 and#177; 0.5 g /mL and 344.4 and#177; 8.2 g /mL as positive control), respectively. The fractions CK-3 and 4 were showed the highest inhibitory activity against AChE with the IC50 value (6.88 and#177; 0.3 g mL and 7.26 and#177; 0.3 g /mL), the fractions CK-5,6,7 and 8 have indicated potent inhibitory activities by compared with galanthamine, which was used as positive control with IC50 value 6.8 and#177; 0.5 g /mL. Among the fractions obtained from the alkaloidal extract, protoberberine-type alkaloids were exerted the most promising activity against both cholinesterases. The present study was described for the first time the in vitro anticholinesterase activity of Corydalis triternata Zucc. as neuroprotective potential and their metabolite profile by LC-Q-TOF-MS. Besides, the anticholinesterase assays on alkaloidal extract and its fractions showed that protoberberine-type alkaloids were determined the most potent inhibitor against AChE and BuChE.

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, IC50 = 2.42 +/- 0.16 mu g/mL) and butyrylcholinesterase (BChE, IC50 = 20.87 +/- 1.01 mu g/mL) at 100 mu g/mL, whereas IC50 values of galanthamine used as the reference were 1.33 +/- 0.11 mu g/mL and 37.69 +/- 2.93 mu g/mL for AChE and BChE, respectively. Beside this, 8-hydroxy-9-methoxycrinine was a strong inhibitor of AChE (IC50 = 6.92 +/- 0.51 mu g/mL), while (+)-9-O-demethylhomolycorine displayed a moderate BChE inhibition (IC50 = 83.57 +/- 1.36 mu g/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 candidatemolecule for future experiments. (C) 2020 SAAB. Published by Elsevier B.V. All rights reserved.

The genus Iris L. (Iridaceae) is a member of geophytes with attractive flowers. There are about 56 Iris taxa growing in Turkey, 24 of which are endemic. A survey of the literature indicates that the research carried out on Iris species are focused on the flavonoid and volatile compounds of the plant. In present study, the dichloromethane and methanol extracts prepared from the rhizomes of 47 Iris taxa growing in Turkey were investigated for their in vitro cholinesterase inhibitory effects against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which the enzymes linked to Alzheimer’s diseases and antioxidant capacities using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging test as well. The Iris extracts studied have been found more active against BChE than AChE. compared with 100 μg/ml galanthamine (89.29 ± 0.96 %) as reference, Iris kerneriana (coded as Y122) and Iris pseudacorus (coded as Y131) methanol extracts had significant BChE inhibition effect (respectively, 80.22 ± 1.04 % and 53.06 ± 1.13 %) at concentration of 200 μg/ml. Among tested samples, methanol extracts of I. kerneriana, I. lazica, I. pseudacorus and I. suaveolens have shown remarkable antioxidant activity at concentration of 2 mg/ml for DPPH compared with gallic acid.

Plants have been used as medicine by mankind to treat health-threatening diseases and still popular to develop new drug candidates. Plants have a combination of phytochemicals also known as secondary metabolites that are naturally occurred gives different therapeutic benefits. Natural products have been recognized as an important role in the drug discovery process moreover the other sources. Presently, over 100 natural product-derived pharmaceuticals are being used in modern medicine. Some of them play as important tools in the immune system exhibiting antiviral potentials. This review presents a survey of natural products and herbal extracts that have indicated broad antiviral activity.

Most of the bulbous plants are known for their medicinal purposes in addition to their ornamental value. Turkey is one of the home country of many beautiful bulbous plants. In continuation of our extensive studies on finding new natural cholinesterase inhibitors from Turkish medicinal plants, Iris L. species were investigated for their in vitro cholinesterase inhibitory effects designed to assess cholinesterase inhibitor activities on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and antioxidant capacities with respect to their neuroprotective potential in this study. The dichloromethane and methanol extracts prepared from the bulbs of 47 Iris taxa were screened by using modified Ellmann method and the highest butyrylcholinesterase inhibitory effect was found in the methanol extract of the bulbs of Iris pseudacorus L. The dichloromethane sub-extract, which is obtained bioactivity-guided fractionation of methanol extract of I. pseudacorus L., was exhibited significant butyrylcholinesterase inhibitory activity (73.65 ± 2.06 %). These active sub-extract was subjected to fractionation on column chromatography and obtained six fractions. Among the fractions, coded as N5 was shown the significant butyrylcholinesterase inhibitory activity (93.78 ± 1.49 %) compared with galanthamine (80.02 ± 0.12 %). Fractionation of N5 on flash chromatography the highest butyrylcholinesterase inhibitory activity of sub-fraction coded as DS-5 was determined as 94.00 ± 1.03 %. The responsible compound from the activity of this sub-fraction was detected as irisolidone glucopyranoside based on its mass data by using LC-ESI-Q/TOF-MS-MS technique.

Medicinal plants have an enormous potential for producing bioactive compounds of great benefit to mankind. There is a great scope for new drug candidates based on traditional medicinal plants throughout the world. The number of drugs derived from medicinal plants that are recently introduced into clinical use is increasing. Besides, numerous of standardized herbal extracts were also approved as phytomedicines by the health authorities to be used in phytotherapy. The drug discovery program from nature in our laboratory involves several steps from plant collection, extraction, HTS of the extracts by using in vitro enzyme inhibitory tests, bioassay-guided fractionation through the isolation and structure elucidation of bioactive compounds. Continuing our researches in the field of anticholinesterase activity, neuroprotective potential of Iris pseudacorus L. have presented in this article.

A new steroidal alkaloid, michainine (1), was isolated from Fritillaria michailovskyi Fomin, along with nine known compounds 2-10 of different classes, including ribonucleoside, steroids, and fatty acids, which were isolated for the first time from this plant. Their structures were elucidated through extensive spectroscopic techniques, as well as by comparing the data in the literature. Furthermore, the dichloromethane fraction of F. michailovskyi showed a positive butyrylcholinesterase inhibitory activity, along with non-cytotoxicity against 3T3 cell line.