Butyrylcholinesterase Inhibitory Effects Research Articles

ANALYSIS OF VOLATILE COMPOUNDS OF ALCEA CALVERTII BOISS. AND ITS ANTIMICROBIAL, ANTICHOLINESTERASE, AND ANTITYROSINASE POTENCY

The research aimed to analyze the volatile compounds by using SPME-GC-MS and to detect anticholinesterase, antityrosinase, and antimicrobial potential of metanol extract of Alceacalvertii Boiss., an endemic species for Türkiye. The inhibitory effects of tyrosinase, acetylcholinesterase, and butyrylcholinesterase of the plant were determined by spectroscopic technique and the plant’s antimicrobial activity was assessed using the agar diffusion method. A total of 18 volatile compounds were specified belonging to terpenes classes. o-cymene (10.60%) and sesquicineole (15.55%) were detected as major volatile components of the species by the SPME-GC-MS technique. Meaningful antimicrobial activity was observed on Candida tropicalis, Enterococcus faecalis, Escherichia coli, Mycobacterium smegmatis, Staphylococcus aureus, and Pseudomonas aeruginosa. The half maximal inhibitory concentration (IC50) value of the plant was determined 60.12 ± 1.75 μg/mL as a result of tyrosinase assay. IC50 value was found 111.54 ± 1.75 μg/mL, according to butyrylcholinesterase inhibition studies. Considering all the findings, it has been determined that the plant includes diverse volatile compounds and showed promising antimicrobial, tyrosinase inhibitory, and moderate butyrylcholinesterase inhibitory effects so Alceacalvertii may be the up-and-coming source of natural medicine for microbial and dermatological diseases although limited to its effects for Alzheimer's disease.

Synthesis and molecular docking studies of 5-trifluoromethoxy-2-indolinones as cholinesterase dual inhibitors.

Background: In Alzheimer's disease, butyrylcholinesterase (BuChE) activity gradually increases, while acetylcholinesterase (AChE) activity decreases or remains unchanged. Dual inhibitors have important roles in regulation of synaptic acetylcholine levels and progression of Alzheimer's disease. Methods: 1-(Thiomorpholin-4-ylmethyl)/benzyl-5-trifluoromethoxy-2-indolinones (6-7) were synthesized. AChE and BuChE inhibitory effects were investigated with Ellman's method. Molecular docking studies were performed for analyzing the possible binding interactions at active sites. Results: Compound 6g was the strongest inhibitor against both AChE (Ki=0.35μM) and BuChE (Ki=0.53μM). It showed higher inhibitory effects than both donepezil and galantamine. Moreover, compound 7m had a higher inhibitory effect than galantamine and the effect was comparable to that of donepezil against both AChE (Ki=0.69μM) and BuChE (Ki=0.95μM). Conclusion: The benzyl substitution compared with 1-(thiomorpholin-4-ylmethyl) group significantly increased both AChE and BuChE inhibitory effects.

Chemical composition, cholinesterase, and α-glucosidase inhibitory activity of the essential oils of some Iranian native Salvia species

BackgroundThe plants from Salvia genus contain widely distributed species which have been used in folk medicine as well as pharmaceutical and food industries.MethodsThe chemical composition of 12 native Iranian Salvia species (14 plants) was identified using gas chromatography-mass spectrometry (GC–MS). Also, the inhibitory activity of all essential oils (EOs) was evaluated toward α-glucosidase and two types of cholinesterase (ChE) using spectrophotometric methods. The in vitro α-glucosidase inhibition assay was performed by the determination of p-nitrophenol (pNP) obtained from the enzymatic dissociation of p-nitrophenol-α-D-glucopyranoside (pNPG) as the substrate. In vitro ChE inhibitory assay was conducted based on the modified Ellman’s procedure using the measurement of 5-thio-2-nitrobenzoic acid produced from the hydrolysis of thiocholine derivatives as the substrate, in the presence of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).ResultsTotally, 139 compounds were detected and caryophyllene oxide and trans-β-caryophyllene were the most abundant compounds in all EOs. The yield of EOs extracted from the plants were also calculated in the range of 0.06 to 0.96% w/w. Herein, α-glucosidase inhibitory activity of 8 EOs was reported for the first time and among all, S. spinosa L. was found to be the most potent inhibitor (90.5 inhibition at 500 μg/mL). Also, the ChE inhibitory activity of 8 species was reported for the first time and our results showed that the BChE inhibitory effect of all EOs was more potent than that of AChE. The ChE inhibition assay indicated that S. mirzayanii Rech.f. & Esfand. collected from Shiraz was the most potent inhibitor (72.68% and 40.6% at the concentration of 500 μg/mL, toward AChE and BChE, respectively).ConclusionsIt seems that native Salvia species of Iran could be considered in the development of anti-diabetic and anti-Alzheimer's disease supplements.

Synthesis and molecular modeling studies of 1-benzyl-2-indolinones as selective AChEinhibitors.

Background: Possible bioisosteres can be developed by replacing the 1-indanone ring (one of three pharmacophore groups) of donepezil with an indoline ring. As H2S donors, thioamide, thiocarbamate and thiourea groups are also critically important. Materials & methods: The 1-benzyl-2-indolinones 6a-n were designed using molecular modeling and synthesized, and their acetylcholinesterase and butyrylcholinesterase inhibitory effects were then investigated. Results: The compounds 6h (inhibition constant [Ki] =0.22μM; selectivity index [SI] =26.22), 6i (Ki=0.24μM; SI=25.83), 6k (Ki=0.22μM; SI=28.31) and 6n (Ki=0.21μM; SI=27.14) were approximately twofold more effective against and >12-fold more selective for acetylcholinesterasecompared with donepezil (Ki=0.41μM; SI=2.12). Analysis of molecular dynamics simulations with compounds 6k and 6n indicated that the preferred binding might be at allosteric binding pocket 4 of the enzyme. Conclusion: Benzyl substitution at the 1-position of the indole ring significantly increased potency and selectivity.

Phytochemical Profiling, Mineral Elements, and Biological Activities of Artemisia campestris L. Grown in Algeria

Artemisia campestris L. is commonly used in folk medicine due to its antioxidant, antidiabetic, nutritional, and culinary properties. Our study assessed the total phenolics contents, antioxidant, and pharmacological activities of various organic extracts prepared from the aerial parts of Artemisia campestris, and its mineral elements and chemical profile were analyzed. ICP-OES was used to analyze the mineral profile and the LC-MS/MS analysis was used to characterize the phytochemical profiling. A series of antioxidant tests were carried out using DPPH, ABTS, beta-carotene, GOR, RP, CUPRAC, and O-Phenanthroline assays. In vitro potent inhibitory actions of A. campestris extracts were investigated to evaluate their anti-cholinesterase, anti-lipase and anti-diabetic activities. The photoprotective effect of the plant was measured by the sun protection factor. The most powerful inhibitor of α-amylase was AcPEE (IC50 = 11.79 ± 0.14 μg/mL), which also showed a significant butyrylcholinesterase inhibitory effect (IC50 = 93.50 ± 1.60 μg/mL). At IC50 = 23.16 ± 0.19 μg/mL, AcEAE showed the most powerful inhibitory effects on acetylcholinesterase. A. campestris was found to have a strong photoprotective ability, absorbing UV radiations with SPF values ranging from 26.07 ± 0.22 to 40.76 ± 0.11. The results showed that A. campestris extract has strong antioxidant activity in all the test samples except for the carotene bleaching assay. The LC/MS-MS results showed that AcDE, AcEAE, and AcBE identified 11 compounds belonging to Polyphenols Compounds. Our result also showed that A. campestris contains a high concentration of essential minerals, including macro-and micro-elements with their values close to the FAO’s recommended concentration. A. campestris has the capacity to improve pharmaceutical formulations, health, and medical research, due to its compositions and potent biological properties.

The Effect of Terpenoids ofDipsacus AsperoidesAgainst Alzheimer's Disease and Development of Simultaneous Analysis by High Performance Liquid Chromatography

Dipsaci Radix has been proved to represent an effective treatment strategy for Alzheimer's disease (AD), but the potential active components in Dipsaci Radix have not been evaluated by an AD-related bioassay. In this study, water fraction of Dipsaci Radix had been shown to have highest inhibitory effect on the AD-related activity tests, including inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and advanced glycation end-product (AGE) formation. Therefore, a bioassay-guided approach yielded eleven terpenoid compounds (DR1-11) isolated from water fraction of Dipsaci Radix. Compounds (DR2,3,7 and 11) were stronger inhibitors of AChE. The BChE inhibitory effect of saponins was more positive than that of iridoids (DR1,4). Compounds (DR6,7,9-11) were good inhibitors of BACE1. Compounds (DR7-11) were more effective than positive control on the inhibition of AGE formation. Moreover, we firstly suggested concomitant new connections between the structure of Dipsaci Radix's isolated terpenoid compounds with AChE inhibitory activities and AGE formation. The study also represented that Dipsaci Radix was therapeutic for treating AD and dipsacus saponin XI (DR11) might be one of its active components. Our findings significantly provided the new foundation of the potential capacity bioactive components from Dipsaci Radix for AD remedy.

Chemical composition, antioxidant and anticholinesterase activity of the essential oil of algerian cachrys sicula L

In this work, in order to explore a new Algerian medicinal plant used in traditional medicine, the essential oil of the leaves of Cachrys sicula L. (Apiaceae) collected from Algeria, obtained by hydrodistillation, was analyzed by GC/MS. Thirty-two compounds were identified accounting for 98.6% of the total oil, which is characterized by a high content of monoterpene hydrocarbons (74.8%). The main constituents of the essential oil were β-pinene (17.9%), sabinene (17.8%), myrcene (12%), and α-pinene (11.4%). In vitro antioxidant activity of the essential oil was assayed by three methods, namely ABTS•+, metal chelating, and DPPH• assays. The antioxidant activity of the oil was higher in the ABTS•+ method. Anticholinesterase activity was screened by the Ellman method against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which are the chief enzymes of Alzheimer’s disease. The results showed mild acetylcholinesterase and good butyrylcholinesterase inhibitory effects.

Anticholinesterase Activity of Eight Medicinal Plant Species: In Vitro and In Silico Studies in the Search for Therapeutic Agents against Alzheimer's Disease.

Many Bangladeshi medicinal plants have been used to treat Alzheimer's disease and other neurodegenerative diseases. In the present study, the anticholinesterase effects of eight selected Bangladeshi medicinal plant species were investigated. Species were selected based on the traditional uses against CNS-related diseases. Extracts were prepared using a gentle cold extraction method. In vitro cholinesterase inhibitory effects were measured by Ellman's method in 96-well microplates. Blumea lacera (Compositae) and Cyclea barbata (Menispermaceae) were found to have the highest acetylcholinesterase inhibitory (IC50, 150 ± 11 and 176 ± 14 µg/mL, respectively) and butyrylcholinesterase inhibitory effect (IC50, 297 ± 13 and 124 ± 2 µg/mL, respectively). Cyclea barbata demonstrated competitive inhibition, where Blumea lacera showed an uncompetitive inhibition mode for acetylcholinesterase. Smilax guianensis (Smilacaceae) and Byttneria pilosa (Malvaceae) were also found to show moderate AChE inhibition (IC50, 205 ± 31 and 221 ± 2 µg/mL, respectively), although no significant BChE inhibitory effect was observed for extracts from these plant species. Among others, Thunbergia grandiflora (Acanthaceae) and Mikania micrantha (Compositae) were found to display noticeable AChE (IC50, 252 ± 22 µg/mL) and BChE (IC50, 314 ± 15 µg/mL) inhibitory effects, respectively. Molecular docking experiment suggested that compounds 5-hydroxy-3,6,7,3′,4′-pentamethoxyflavone (BL4) and kaempferol-3-O-α-L-rhamnopyranosyl-(1⟶6)-β-D-glucopyranoside (BL5) from Blumea lacera bound stably to the binding groove of the AChE and BChE by hydrogen-bond interactions, respectively. Therefore, these compounds could be candidates for cholinesterase inhibitors. The present findings demonstrated that Blumea lacera and Cyclea barbata are interesting objects for further studies aiming at future therapeutics for Alzheimer's disease.

Comprehensive evaluation of two Astragalus species (A. campylosema and A. hirsutus) based on biological, toxicological properties and chemical profiling

Astragalus L. (Fabaceae) is an important genus with numerous species having various traditional medicinal uses making them of interest for scientific investigations to ascertain their therapeutic benefits. In the present study, the quantitative polyphenolic profiles of methanolic extracts from different parts (leaves, flowers, and roots) of two endemic Astragalus species growing in Turkey, i.e. A. campylosema Boiss. and A. hirsutus Vahl were determined, along with their antioxidant and enzyme inhibitory properties. A. campylosema and A. hirsutus extracts showed varying total phenolic (25.80–40.60 and18.59–29.46 mg GAE/g, respectively) and total flavonoid (11.21–105.91 and 16.06–131.91 mg RE/g, respectively) contents. HPLC-MS/MS revealed rutin to be the predominant phenolic compound in all the extracts of A. campylosema and leaf extract of A. hirsutus (133.53–752.42 μg g−1), while hyperoside was the major one in the flower and root extracts of A. hirsutus (2014.07 and 123.13 μg g−1, respectively). In DPPH and ABTS assays, radical scavenging capacity was demonstrated by all extracts of A. campylosema (47.13–48.10 and 87.03–115.36 mg TE/g, respectively) and A. hirsutus (17.82–38.67 and 47.84–57.29 mg TE/g, respectively). Reducing activity was also displayed by the extracts in CUPRAC and FRAP assays (A. campylosema: 83.06–135.20 and 59.15–90.19 mg TE/g, respectively; A. hirsutus: 53.02–83.42 and 31.25–43.25 mg TE/g, respectively). All extracts were also found to act as metal chelators (12.32–21.45 mg EDTAE/g) and exhibited total antioxidant capacity ranging from 1.16 to 1.60 mmol TE/g, in phosphomolybdenum assay. Acetyl- and butyryl-cholinesterase inhibitory effects were observed by all the extracts of the two species (1.56–4.99 mg GALAE/g). Anti-hyperpigmentation potential by inhibiting tyrosinase (54.55–67.35 mg KAE/g) was reported as well. Carbohydrate hydrolyzing enzymes, amylase and glucosidase were also inhibited (0.22–1.03 mmol ACAE/g). Overall, A. campylosema extracts showed relatively better antioxidant and enzyme inhibitory potentials compared to A. hirsutus extracts. Strikingly, A. hirsutus extracts was found to have higher AGE inhibition activity than A. campylosema. Although the cytotoxic effect of three different organs obtained from A. campylosema and A. hirsutus increased depending on the dose (from 10 to 200 μg/mL), it was found that both plant extracts did not show a genotoxic effect at the highest concentration of 200 μg/mL. Indeed, data amassed from this current scientific work showed the two selected Astragalus species to be rich in bioactive polyphenols that could be responsible for the various pharmacological activities and hence demands to be further explored for their possible applications as natural health promoting agents.

Synthesis, Characterization, and Inhibition Study of Novel Substituted Phenylureido Sulfaguanidine Derivatives as α-Glycosidase and Cholinesterase Inhibitors.

A series of six N-carbamimidoyl-4-(3-substituted phenylureido)benzenesulfonamide derivatives were synthesized by reaction of sulfaguanidine with aromatic isocyanates. In vitro and in silico inhibitory effects of the novel ureido-substituted sulfaguanidine derivatives were investigated by spectrophotometric methods for α-glycosidase (α-GLY), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes associated with diabetes mellitus (DM) and Alzheimer's disease (AD). N-Carbamimidoyl-4-{[(3,4-dichlorophenyl)carbamoyl]amino}benzene-1-sulfonamide (2f) showed AChE and BChE inhibitory effects, with KI values of 515.98±45.03 nM and 598.47±59.18 nM, respectively, while N-carbamimidoyl-4-{[(3-chlorophenyl)carbamoyl]amino}benzene-1-sulfonamide (2e) showed strong α-GLY inhibitory effect, with KI values of 103.94±13.06 nM. The antidiabetic effects of the novel synthesized compounds are higher than their anti-Alzheimer's effects, because the inhibition effect of the compounds on the α-GLY with diabetic enzyme is greater than the effect on esterase enzymes. Indeed, inhibition of the metabolic enzymes is important for the treatment of DM and AD.

Volatile and phenolic profiling of a traditional medicinal plant, Hypericum empetrifolium with in vitro biological activities

Ethnopharmacological relevanceHypericum empetrifolium Willd is a member of the Hypericaceae family, mainly known in southern Greece, and western Turkey. Being a centuries-old medicinal plant, the aerial parts of the plant have been used for the treatment of herpes, kidney stones, gastric ulcer, and also for their anti-helminthic, and diuretic purposes traditionally. Aim of the studyThe current study aimed to investigate the phytochemical profiles of the essential oil, and two ethanol extracts prepared from the aerial parts (H. empetrifolium aerial parts extract – HEA), and roots of the plant (H. empetrifolium roots extract – HER), and to provide data on antioxidant, anticholinesterase, antityrosinase, antiurease, cytotoxic, and antimicrobial activities of the extracts. Materials and methodsIn this study, volatile and phenolic compounds of the HEA and HER were analyzed by GC-MS and LC-MS/MS, respectively. Antioxidant potential of the extracts was clarified by using DPPH radical scavenging assay, ABTS cation radical assay, and the CUPRAC assay. Acetylcholinesterase, butyrylcholinesterase, urease, and tyrosinase inhibitory activity assays were used to determine enzyme inhibition capacity of the extracts. Cytotoxic activity of the extracts was established by using XTT assay. The antimicrobial activity of the extracts was determined by the microbroth dilution technique. ResultsThe major compounds of the essential oil were revealed as alloaromodendrene (24.7%), α-pinene (14.7%), β-pinene (10.7%), and α-terpineol (7.7%) by the GC-MS analysis. According to the LC-MS/MS analysis results, quinic acid was the most abundant constituent in both extracts with 20612.42 ± 169.02 μg/g extract in HEA extract, and with 2254.34 ± 18.49 μg/g extract in HER extract, respectively. The HEA extract was also found to be rich in terms of chlorogenic acid (5583.14 ± 38.52 μg/g extract), isoquercitrin (3076.77 ± 40.92 μg/g extract), and malic acid (2822.90 ± 31.90 μg/g extract). HEA extract exhibited a significant antioxidant effect with an IC50 value of 11.98 ± 0.22 μg/mL according to the DPPH radical scavenging assay. Similar results were obtained with the ABTS cation radical assay, and the CUPRAC assay. HER extract showed a strong butyrylcholinesterase inhibitory effect with 88.69 ± 0.62% at 200 μg/mL concentration. Both extracts were considered to have moderate anti-tyrosinase activity compared to the standard at 200 μg/mL. The best antimicrobial activity was obtained for HEA against C. parapsilosis with an MIC value of 4.88 μg/mL. HEA also exhibited antifungal activity against C. tropicalis with 19.53 μg/mL. Only HER exhibited low cytotoxicity on A498 renal cell lines with 60.6% cell viability. ConclusionUnquestionably, H. empetrifolium Willd has ethnopharmacological importance according to these results, and further investigations are required to evaluate other therapeutic properties of the plant.

Comparative effects of berberine and piperine on the neuroprotective potential of neostigmine

This study examined effect of berberine and piperine on neuroprotective potential of neostigmine in the management of neurological disorders. Berberine and neostigmine were weighed (30g), dissolved in distilled water (30mL) separately, while, 30mg piperine was dissolved in ethanol (0.45mL), made up to 30mL with distilled water. Antioxidant activities in 2, 2-diphenyl-1-picrylhydrazyl radical (DPPH), 2, 2-azinobis (3-ethylbenzothiazoline-6-sulfonate) radical (ABTS), Fe-chelation, ferric reducing properties (FRAP), nitric oxide (NO) and hydroxyl (OH) radical scavenging abilities and Fe2+, cisplatin and sodium nitroprusside (SNP) induced lipid peroxidation (LPO), and acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidase (MAO) activities were assessed in vitro. The result revealed that tested compounds inhibited enzymes activities dose-dependently. However, berberine (IC50=0.17mg/mL) had slight higher AChE inhibitory effect than piperine and neostigmine (p<0.05). Also, berberine had the highest BChE inhibitory effect (IC50=0.16mg/mL) while piperine exhibited the highest MAO inhibitory effect (IC50=0.21mg/mL). Berberine, piperine and neostigmine exhibited high antioxidant properties and inhibited Fe2+, cisplatin and SNP induced LPO. Both alkaloids demonstrated antiradical scavenging ability comparable to neostigmine action against Alzheimer's disease (AD). The modulatory and antioxidant berberine and piperine properties on these enzymes (AChE, BChE and MAO) could be possible underlying mechanisms in employing these compounds as a complementary therapy in neurodegenerative diseases (NDDs) management.

Chemical Composition, Antioxidant Potential and Enzymes Inhibitory Properties of Globe Artichoke By-Products.

In this study, chemical composition and in vitro biological activities of artichoke by-products (leaves, floral stems and bracts) issued from two Tunisian varieties were evaluated. Analysis was performed by means of high-performance liquid chromatography with diode array detection coupled to electrospray ionization mass spectrometric (LC/DAD/ESI-MS). Total phenolic (TPC) and flavonoid (TFC) contents as well as the antioxidant activity conducted by three complementary methods, DPPH, ABTS and FRAP tests, were performed for each sample. Enzyme inhibitory effects against acetylcholinesterase, butyrylcholinesterase and α-amylase were also studied. Results showed that TPC and TFC varied according to variety as well as the plant part. Bracts presented the highest TPC values (10-15 mg GAE/g DW), while leaves were distinguished by the highest TFC values (52-58 mg EQ/g DW). In vitro assays showed that Violet d'Hyères bracts and Blanc d'Oran leaves present the most antioxidant activities (30.040 and 20.428 mgET/gDW, respectively, by the DPPH method). Leaves demonstrated the highest acetylcholinesterase and butyrylcholinesterase inhibitory effects. Moreover, all organs displayed a noticeable inhibition towards α-amylase. LC/DAD/MS analysis revealed that artichoke by-products are a potential source of biopharmaceuticals such as luteolin derivatives from leaves and mono/dicaffeoylquinic acids in the other parts. This research demonstrates that globe artichoke by-products, unexploited in our country, are a promising source of natural health promoting compounds with potential applications in the food and pharmaceutical industries.

Isolation and Identification of Cholinesterase Inhibitors from the Bulbs of Iris pseudacorus L.

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.

Phytochemical and biological investigations on two Nepeta species: Nepeta heliotropifolia and N. congesta subsp. cryptantha.

In the present study, the essential oil and aroma compositions of Nepeta heliotropifolia (NH) and N. congesta subsp. cryptantha (NC) were determined by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detector (GC/FID), and their phenolic compounds by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, antioxidant, cytotoxic, anticholinesterase, urease, and tyrosinase activities of essential oils obtained from NH and NC aerial parts and ethanol extracts prepared from different parts of NH and NC were investigated. The major constituent of water-distilled essential oils was found to be germacrene D (36.7% and 38.5%, respectively), and their main aroma component was eucalyptol (48.0% and 24.7%, respectively). Among the studied parts of NH and NC, their flowers extracts were found to be the richest in phenolic compounds and in which the most abundant compound was rosmarinic acid (8,909.91 and 4,317.20μg/g, respectively). NH and NC flower extracts exhibited also strong antioxidant activity in DPPH, ABTS, and CUPRAC assays. Among the tested samples, NH essential oil indicated the best cytotoxic effect against PDF, HT-29, and MCF-7 (IC50 52.34, 25.89, and 44.70μg/ml, respectively), and the highest butyrylcholinesterase (77.21±1.12% inhibition) and moderate acetylcholinesterase (41.36±0.69% inhibition) inhibitory activities. PRACTICAL APPLICATIONS: This is the first report on the essential oil and aroma compositions, the phenolic compounds, the antioxidant with total phenolic and flavonoid contents, cytotoxic, anticholinesterase, urease, and tyrosinase activities of Nepeta heliotropifolia and N. congesta subsp. cryptantha, except for their essential oil compositions. The reported results suggested that Nepeta heliotropifolia and N. congesta subsp. cryptantha flowers being rich in rosmarinic acid and having strong antioxidant potential, and NH essential oil possessing significant cytotoxic and butyrylcholinesterase inhibitory effect could be source for nutraceutical, food, and drug industries.

A caffeic acid-ferulic acid hybrid compound attenuates lipopolysaccharide-mediated inflammation in BV2 and RAW264.7 cells

In the present study, we synthesized and evaluated the anti-inflammatory effects of the two component hybrids, caffeic acid (CA)-ferulic acid (FA), FA-Tryptamine (Trm), CA-Piperonyl Triazol (PT) and FA-PT. Of these five hybrids, CA-FA had the most potent inhibitory effect on butyrylcholinesterase (BuChE) activity. The CA containing hybrids, CA-FA, CA-Trm, and CA-PT, dose-dependently inhibited LPS-induced nitric oxide (NO) generation in BV2 cells, whereas FA-PT, FA-Trm, CA, FA, Trm, and PT did not. Although CA-FA, CA-Trm and CA-PT had similar inhibitory effects on LPS-induced NO generation, CA-FA best protected BV2 cells from LPS-induced cell death. CA-FA, but not CA or FA, dose-dependently inhibited LPS-induced up-regulations of NO synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions in BV2 and RAW264.7 cells. Furthermore, CA-FA inhibited LPS-induced iNOS, COX-2, interleukin-6, and interleukin-1β mRNA expressions in BV2 cells. CA-FA also inhibited the LPS-induced phosphorylations of STAT3, Akt, and IκB and selectively inhibited LPS-induced NF-κB activation. Overall, our data suggest that CA-FA has BuChE inhibitory effects and down-regulates inflammatory responses by inhibiting NF-κB, which indicates CA-FA be viewed as a potential therapeutic agent for the treatment of inflammatory diseases of the peripheral system and central nervous systems.

New biphenanthrenes with butyrylcholinesterase inhibitory activitiy from Cremastra appendiculata

Encouraged by the in vitro potent inhibitory activity on butyrylcholinesterase (BChE) of 95% ethanol extract of Cremastra appendiculata (D. Don) Makino tubers, a further phytochemical investigation on C. appendiculata tubers was conducted, which led to the isolation of a pair of new biphenanthrene atropisomers, namely cremaphenanthrene F-G (1–2). Their structures were elucidated on the basis of extensive spectroscopic analyses and chemical method. It is the first time that biphenanthrene atropisomers have been isolated from the plant kingdom. Compound 1 showed potent BChE inhibitory effect with IC50 value of 14.62 ± 2.15 μM. Compound 2 exhibited weak BChE inhibitory effect with IC50 value of 79.56 ± 0.78 μM. Meanwhile, 1 and 2 were found to be inactive for acetylcholinesterase (AChE) inhibition. These findings suggested that compound 1 was a promising selective BChE inhibitor for AD prevention and treatment.

Neuroprotective potential of phenolic extracts of &lt;i&gt;Capsicum frutescens&lt;/i&gt; as an inhibitor of monoamine oxidase and cholinesterase activities

In this study, we investigated the in vitro antioxidant activity of the extracts from ripe and unripe fruits of Capsicum frutescens . The effects of the extracts on three enzymes which are associated with Parkinson's disease (PD) were also investigated together with quantitation of total phenol, flavonoid and non-flavonoid contents of the extracts. Activities of mitochondrial monoamine oxidase (MAO), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) from rat brain were determined in the presence of the extracts. 1, 1-diphenyl-2- picrylhydrazyl (DPPH) and OH radicals scavenging abilities, as well as membrane stabilizing effect of the extract via inhibition of Fe 2+ -induced lipid peroxidation in rat brain tissue homogenate were assessed. The results revealed that the extracts exhibited mitochondrial MAO, AChE and BChE inhibitory effects in concentrationdependent manner, with the unripe fruit extract showing significantly higher (P<0.05) inhibitory effects than the ripe fruit extract. However, the ripe fruit extract had significantly higher total phenol and flavonoid contents, as well as exhibited significantly higher (P<0.05) DPPH free radical scavenging and membrane stabilizing effects. The observed antioxidant and enzyme inhibitory properties of ripe and unripe pepper ( C. frutescens ) fruits extracts could be an interplay among their constituent polyphenols. This could be a justification for their use as nutraceutical/dietary intervention in the management of neurodegenerative diseases, especially PD. Collectively, these findings suggest that C. frutescens could serve as a functional food/nutraceutical in the management of PD and our further studies will be directed towards characterization of the biomolecules involved and their mechanism(s) of action in appropriate models. Keywords: Monoamine oxidase, Cholinesterases, Capsicum spp , Neurodegenerative diseases, Functional foods

Impact of different geographical locations on varying profile of bioactives and associated functionalities of caper (Capparis spinosa L.)

Capparis spinosa L. (caper), is a traditionally used medicinal plant and widely studied for its biological properties. We aimed for the first time to compare the biological and phenolic fingerprints of C. spinosa buds, collected from Morocco, Turkey, and Italy. Phenolic compounds, fatty acids, and essential oils were profiled by chromatographic techniques. Enzymes inhibitory activities of different extracts were tested by spectrophotometric methods. Antioxidant capacity was evaluated by different assays including free radical scavenging, reducing power, metal chelating and phosphomolybdenum. Moroccan sample showed the highest phenolic content across all extraction types followed by Italian and Turkish. Rutin was detected as main compounds in the extracts and the Italian decoction extract had highest rutin content. Moroccan samples exhibited the highest activity in microwave and Soxhlet extracts. The highest acetylcholinesterase inhibitory activity was observed in Turkish Soxhlet and Moroccan samples. The best butyrylcholinesterase inhibitory effects were also detected in the Italian extracts. The predominant fatty acid was α-linoleic acid (C 18:3 ω3; 28.65%), observed from Turkish sample. n-Hexadecanoic acid was the main component in the essential oils (13.9%, 25.03%, and 36.67% for Italian, Turkish, and Moroccan samples, respectively). Our results strongly advocate that future formulation of C. spinosa as active ingredient should also take into account the geographical origins and extraction techniques.

Essential Oil Composition and Anticholinesterase Activity Evaluation of Achillea fragrantissima Growing Wild in Jordan

ABSTRACTThe composition of hydro-distilled oils of Achillea fragrantissima inflorescence (fresh and dry) at the pre- and flowering stages was evaluated by Gas Chromatography/Mass Spectrometry (GC/MS). Additionally, the essential oil and solvent extracts of the dried inflorescence were assayed for their inhibitory effect against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All essential oils were rich oxygenated monoterpenes especially in the flowering stage (69.27% fresh, 81.72% dry). The hydro-distilled oil of the dried inflorescence showed low activity as AChE inhibitor (IC50 0.05 ± 0.01 μg μL−1). The ethyl acetate fraction (IC50 0.063 ± 0.02 μg μL−1) showed the highest AChE inhibitor activity, whereas the hydro-alcoholic fraction had the highest BChE inhibitory effect (IC50 0.037 ± 0.010 μg μL−1). Results proposed the possible applications of A. fragrantissima flower extracts as coadjuvants in the treatment of cognitive diseases including Alzheimer’s disease.