Butyrylcholinesterase Inhibitory Activity Research Articles

Chemical profile, acetylcholinesterase, butyrylcholinesterase, and prolyl oligopeptidase inhibitory activity of Glaucium corniculatum subsp. refractum

Papaveraceae is one of the prominent alkaloid-containing families, and plants of the genus Glaucium (Papaveraceae) are known for their bioactive alkaloids. Glaucium species have been used in traditional medicine in Turkey as an analgesic, narcotic, sedative, and antitussive. In this study, it was planned to evaluate the inhibitory activity of an alkaloidal extract of Glaucium corniculatum subsp. refractum on acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and prolyl oligopeptidase (POP), as well as exploring the chemical profile of the plant by using Gas Chromatography-Mass Spectrometry (GC-MS). The AChE, BuChE and POP inhibition activities of the alkaloidal extract of G. corniculatum subsp. refractum were determined spectrophotometrically. A rapid GC-MS method was used to identify alkaloids that could be responsible for these inhibition activities. In total, eleven alkaloids were identified in the alkaloid extract of the plant by GC-MS. Allocyptopine (52.92%) and protopine (25.38%) were found as the major constituents. The alkaloidal extract of G. corniculatum subsp. refractum showed potent AChE inhibitory activity (IC50:1.25 µg/mL) and BuChE inhibitory activity (IC50: 7.02 µg/mL). The extract also showed a remarkable inhibitory effect on POP with an IC50 value of 123.69 µg/mL. This study presents the first GC-MS investigation and POP inhibitory activity of G. corniculatum subsp. refractum.

Determination of essential oil and biological activities of Hypericum ternatum Poulter and H. scabrum L. species collected from different localities: is H. scabrum an alternative to multifunctional species ST JOHN'S WORT (H. perforatum)?

The importance of Hypericum L. species, being used in traditional medicine, in the scientific world is increasing day by day. Hypericum species are plants that have been used in the treatment of many diseases for a long time and have healing properties. In the current study, the essential oil compositions of Hypericum scabrum L. and H. ternatum Poulter collected from different localities in Turkey were determined by GC-MS/FID. In addition, their antioxidant, cytotoxic, and antimicrobial activities with their enzyme inhibitory potentials (cholinesterase, urease, tyrosinase, elastase, and collagenase) were investigated. Also, in vitro and in silico studies of the major components of the species have been carried out on the studied enzymes. It was determined that four H. scabrum samples mainly contained α-pinene (55.99%-62.80%) while three H. ternatum samples contained 2-methyloctane (9.45%-22.39%) and α-pinene (12.75%-33.08%). While H. scabrum essential oils possessed significant biological activity potential except for the antimicrobial activity, H. ternatum samples did not. All essential oil samples of H. scabrum exhibited a high cytotoxic effect (IC50 21.67 ± 0.34 to 34.67 ± 0.45 μg/mL) against colon cancer cell line (HT-29) and indicated higher acetyl-(Inhibiton% 83.30 ± 1.90 to 93.08 ± 1.04) and butyryl-cholinesterase (Inhibiton% 80.58 ± 1.19 to 93.28 ± 1.99) inhibitory activity than the standard compound, galantamine. Furthermore, all samples of H. scabrum showed high tyrosinase (Inhibiton% 69.00 ± 1.64 to 95.25 ± 1.42) and elastase (Inhibiton% 27.58 ± 0.34 to 36.69 ± 0.18) inhibitory effects. These biological activity results indicated that H. scabrum essential oil could be used in the cosmetic and pharmaceutical industries.

A comparative study of physicochemical properties, antioxidant and enzyme inhibition activities of oils extracted from seeds of seven new sunflower (Helianthus annuus L.) lines

This study was aimed to evaluate the physicochemical properties and chemical profile of seeds oil obtained from new seven sunflower (Helianthus annuus L.) lines as well as their antioxidant and enzyme inhibition activity. The seeds powder was extracted by maceration in n-hexane. The oil content of the seven lines was ranged from 20.04% to 36.65% and was either yellow or pale yellow in color. No significant variations were observed on the refractive index (1.46 unit) of the oil. Oils of the seven lines were significantly (p ? 0.05) different in their saponification values (32.13-282.66 mg KOH/g oil), peroxide values (1.76-13.26 mg KOH/g-oil), acid values (0.016?1.766 mg KOH/g oil) and free fatty acids content (6.26-72.23 mg KOH/g-oil). The chemical profile of the oil revealed that line APO42 contained the highest amount of monounsaturated fatty acids (55.9%). All the seven lines contained a considerable amount of linoleic acid (27.5%- 42.5%), and it represented the major compound in lines BOH3 (42.5%) and H1733 (39.8%). The variation was remarkable in their oleic acid content where the highest amount was observed in lines APO42 (55.4%) and APO43 (42.2%), respectively. Lines BOH3, APO43, APO41, and H1733 exerted the best total antioxidant activity in addition to their capacity to reduce Cu2+ and Fe3+, while lines H1733 and APO43 had a metal chelating activity as well. All oils showed weak acetylcholinesterase, butyrylcholinesterase, α-glucosidase and α-amylase inhibitory activities. Only four lines showed considerable enzyme inhibitory activity against tyrosinase enzymes. Multivariance analysis suggested that linoleic acid participated in the observed biological activity of the oils. In conclusion, these new lines might contribute to the nutritional and phytotherapeutic properties of sunflower oil in addition to other industrial applications.

Phenolic profile, antioxidant and enzyme inhibitory activity of the ethyl acetate, methanol and water extracts of Capparis spinosa L.

In this study, it was aimed to determine the phytochemical compositions and biological activities of ethyl acetate (EtOAc), methanol (MeOH) and water extracts obtained from the aerial parts of Capparis spinosa L. As a result of spectrophotometric analyzes, MeOH extract was found to be richer in terms of both phenolics and flavonoids compared to other extracts [81.45 mg GAEs (gallic acid equivalent)/g and 36.57 mg RE (rutin equivalent)s/g, respectively], while chromatographic analyzes showed that the extract in question contains a significant amount of hepseridin (72927.48 µg/g), quercetin (1335.88 µg/g), hyperoside (1227.73 µg/g), and 4-hydroxybenzoic acid (924.08 µg/g). Phosphomolybdenum, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging, Cupric Reducing Antioxidant Power (CUPRAC) and Ferric Reducing Antioxidant Power (FRAP) reducing and ferrous ion chelating activity tests resulted in superiority of MeOH extract [371.0, 44.93, 56.46, 91.77, 52.61 mg TEs (trolox equivalent)/g and 14.85 mg EDTAEs/g, respectively]. On the other hand, EtOAc extract exhibited higher activity than other extracts in acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase, and α-glucosidase inhibitory activity tests [3.29, 2.12 mg GALAEs (galanthamine equivalent)/g, 541.01 and 1584.20 mg ACEs (acarbose equivalent)/g, respectively]. The tyrosinase inhibitory activity test resulted in the superiority of MeOH extract [41.90 mg KAEs (kojic acid equivalent)/g]. A strong correlation was determined between the phenolic and flavonoid contents of the extracts and their antioxidant activities.

Design, synthesis, and biological evaluation of carbamate derivatives of N-salicyloyl tryptamine as multifunctional agents for the treatment of Alzheimer's disease

In this study, we designed, synthesized, and evaluated a series of carbamate derivatives of N-salicyloyl tryptamine as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). After screening the acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibitory activities, target compound 1g stood out as a mixed type reversible dual inhibitor of AChE and BChE. In addition, molecular docking studies were conducted to explore the actions on AChE and BChE. The results showed that 1g could decrease the level of pro-inflammatory cytokines NO, iNOS, IL-6, TNF-α, and ROS, increase the level of anti-inflammatory cytokines IL-4, and inhibit the aggregation of Aβ1-42. Moreover, the administration of 1g suppressed the activity of AChE in the brain. In a word, the compound 1g is effective for improving learning and memory behavior, blood-brain barrier permeation, pharmacokinetics, ChE inhibition, and anti-neuroinflammation. It may be considered as a promising multi-functional therapeutic agent for further investigation for the treatment of AD.

2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis, biological evaluation, molecular docking, and pharmacokinetic studies

• 2-methylindole analogs were designed, synthesized and characterized. • The target 2-methylindole analogs ( 4a–4j ) were evaluated for their inhibitory potential against glutathione S-transferase (GST), acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory activities. • Molecular docking studies were conducted to correlate the in vitro results and to identify possible mode of interactions at the active pocket site of the receptors. • The pharmacokinetic studies of 2-methylindole analogs were carried out using SwissADMET analyses. In this study, we aimed to (i) synthesize new 2-methylindole analogs containing various amino structures, pyrrolidine, piperidine, morpholine, and substituted phenyl groups through structural and molecular modifications, (ii) evaluate the pharmaceutical potential of 2-methylindole analogs via assessing enzyme inhibitory activity against glutathione S-transferase (GST), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), (iii) predict ADMET and pharmacokinetic properties of the synthesized 2-methylindole analogs, (iv) reveal the possible interactions between the synthesized 2-methylindole analogs with GST, AChE, and BChE enzymes using several molecular docking software. In vitro enzyme inhibition assays showed that the synthesized indole analogs exhibited moderate to good inhibitory activities against GST, AChE, and BChE enzymes. Briefly, the inhibitory activities of the analogs 4b and 4i against AChE, 4a and 4b against BChE, and analogs 1 and 4i against GST were detected to be higher or close to the standard inhibitor compounds. The analog 4b was detected to have the best inhibitory activity against both AChE and BChE enzymes with the lowest IC 50 values as 0.648 µM for AChE and 0.745 µM for BChE. The analyses of enzyme inhibition relationship with the synthesized analogs could help to design new analogs for the inhibitors of cholinergic and glutathione pathways based on the indole derivatives.

Synthesis of Sulfanoquinoxaline-2,3-Dione Hydrazones Derivatives as a Selective Inhibitor for Acetylcholinesterase and Butyryl Cholinesterase

Some Sulfanoquinoxaline-2,3-diones hydrazone derivatives (1-8) were synthesized from the reactions of 2,3-dioxoquinoxaline-6-sulfonohydrazine with seven substituted benzaldehydes and acetophenone. All the synthesized compounds were biologically evaluated against cholinesterase’s (acetylcholinesterase and butyryl cholinesterase). Compounds 1-8 were found to be a good selective inhibitor for acetylcholinesterase and butyryl cholinesterase. Among the series, compounds 3 (IC50 = 75 ± 10 µg/mL) and 5 (IC50 = 80 ± 10 µg/mL) were found to be the most active inhibitors against acetylcholinesterase, while compounds 6 (IC50 = 110 ± 10 µg/mL), 8 (IC50 = 130 ± 10 µg/mL) and 7 (IC50 = 150 ± 10 µg/mL), were found to be most active inhibitor against butyryl cholinesterase. The IC50 values for all the synthesized compounds were lower than standard, eserine (IC50 = 70 ± 20 µg/mL). Their considerable acetylcholinesterase and butyryl cholinesterase inhibitory activities make them a good candidate for the development of selective acetylcholinesterase and butyryl cholinesterase inhibitors.

Synthesis of Some Phenylisoindoline-1,3-Diones and their Acetylcholinesterase and Butyryl Cholinesterase Inhibitory Activities

Aims: To synthesize some phthalimides derivatives and evaluate the compounds for their possible biological properties.
 Methods: The substituted phenylisoindoline-1,3-dione were synthesized from the reactions of N-phenyl phthalimide with different substituted aromatic aldehyde. The synthesized compounds were characterized using nuclear magnetic resonance spectroscopic analysis. The acetylcholinesterase and butyryl cholinesterase inhibitions were determined by Spectro photochemical analysis of acetylthiocholine and butyryl choline chloride.
 Results: Compounds 6 (IC50 = 30±3 µg/mL) and 4 (IC50 = 141±60 µg/mL) were found to be the most active inhibitors against acetylcholinesterase, while compounds 4 (IC50 = 102±10 µg/mL), 5 (IC50 = 105 ± 20 µg/mL) and 2 (IC50 = 190 ± 10 µg/mL), were found to be most active inhibitor against butyryl cholinesterase.
 Conclusion: The considerable acetylcholinesterase and butyryl cholinesterase inhibitory activities of the synthesized compounds makes them good candidates for the development of selective acetylcholinesterase and butyryl cholinesterase inhibitors.

Monoterpene indole alkaloids from Vinca minor L. (Apocynaceae): Identification of new structural scaffold for treatment of Alzheimer's disease

One undescribed indole alkaloid together with twenty-two known compounds have been isolated from aerial parts of Vinca minor L. (Apocynaceae). The chemical structures of the isolated alkaloids were determined by a combination of MS, HRMS, 1D, and 2D NMR techniques, and by comparison with literature data. The NMR data of several alkaloids have been revised, corrected, and missing data have been supplemented. Alkaloids isolated in sufficient quantity were screened for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7) and butyrylcholinesterase (BuChE; E.C. 3.1.1.8) inhibitory activity. Selected compounds were also evaluated for prolyl oligopeptidase (POP; E.C. 3.4.21.26), and glycogen synthase 3β-kinase (GSK-3β; E.C. 2.7.11.26) inhibition potential. Significant hBuChE inhibition activity has been shown by (−)-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1H-indole with an IC50 value of 0.65 ± 0.16 μM. This compound was further studied by enzyme kinetics, along with in silico techniques, to reveal the mode of inhibition. This compound is also predicted to cross the blood-brain barrier (BBB) through passive diffusion.

Chemical Composition, Antioxidant, Antimicrobial and Cholinesterase Inhibitory Activities of Essential Oils from the Leaves and Rhizomes of Acorus macrospadiceus (Yamamoto) F. N.Wei et Y. K. Li

Acorus macrospadiceus is an aromatic herb that is widely distributed in southwest China. However, reports on the biological activities of its essential oil (EO) are limited. In the present study, the chemical composition, antioxidant, antimicrobial and cholinesterase inhibitory activities were determined for essential oils extracted from the leaves and rhizomes of this species. The essential oils were extracted by hydrodistillation and analysed by gas chromatography/mass spectrometry (GC/MS) and gas chromatography with a flame ionization detector (GC/FID). Antioxidant activity was examined using DPPH, ABTS and FRAP assays. Antimicrobial activity was evaluated by determining the minimum inhibitory concentrations (MICs) and minimum microbiocidal concentrations (MMCs). Acetylcholinesterase and butyrylcholinesterase inhibitory activities of the essential oils were also tested to evaluate the potential effect of the EOs on neurodegenerative disease. A total of 15 and 19 components were identified in the leaf and rhizome EOs, representing 99.24% and 98.35% of the total composition, respectively. Estragole was found to be the most abundant compound at 98.14% and 94.69% of the leaf and rhizome EOs, respectively. The essential oils displayed weak antioxidant and acetylcholinesterase inhibitory activities. The essential oils showed higher inhibitory effects against Candida albicans than other strains, with a MIC of 3.13 mg/mL, indicating possible use in the treatment of Candida infections.

Chemical Composition and Biological Activities of Essential Oils from the Leaves, Stems, and Roots of Kadsura coccinea.

The chemical composition and biological activities of the essential oils from the leaves, stems, and roots of Kadsura coccinea (K. coccinea) were investigated. The essential oils were extracted by hydro distillation and analyzed by gas chromatography mass spectrometry (GC-MS) and gas chromatography with flame ionization detector (GC-FID). Antioxidant activities of the essential oils were examined with DPPH radical scavenging assay, ABTS cation radical scavenging assay, and ferric reducing antioxidant power assay. Antimicrobial activities were evaluated by determining minimum inhibitory concentrations (MIC) and minimum microbiocidal concentrations (MMC). Acetylcholinesterase and butyrylcholinesterase inhibitory activity of the essential oils were also tested. A total of 46, 44, and 47 components were identified in the leaf, stem, and root oils, representing 95.66%, 97.35%, and 92.72% of total composition, respectively. The major compounds of three essential oils were α-pinene (16.60–42.02%), β-pinene (10.03–18.82%), camphene (1.56–10.95%), borneol (0.50–7.71%), δ-cadinene (1.52–7.06%), and β-elemene (1.86–4.45%). The essential oils were found to have weak antioxidant activities and cholinesterase inhibition activities. The essential oils showed more inhibitory effects against Staphylococcus aureus (S. aureus) than those of other strains. The highest antimicrobial activity was observed in the root oil against S. aureus, with MIC of 0.78 mg/mL. Therefore, K. coccinea essential oils might be considered as a natural antibacterial agent against S. aureus with potential application in food and pharmaceutical industries.

Active Targeted Nanoemulsions for Repurposing of Tegaserod in Alzheimer's Disease Treatment.

Background and Purpose: The activation of 5-HT4 receptors with agonists has emerged as a valuable therapeutic strategy to treat Alzheimer’s disease (AD) by enhancing the nonamyloidogenic pathway. Here, the potential therapeutic effects of tegaserod, an effective agent for irritable bowel syndrome, were assessed for AD treatment. To envisage its efficient repurposing, tegaserod-loaded nanoemulsions were developed and functionalized by a blood–brain barrier shuttle peptide. Results: The butyrylcholinesterase inhibitory activity of tegaserod and its neuroprotective cellular effects were highlighted, confirming the interest of this pleiotropic drug for AD treatment. In regard to its drugability profile, and in order to limit its peripheral distribution after IV administration, its encapsulation into monodisperse lipid nanoemulsions (Tg-NEs) of about 50 nm, and with neutral zeta potential characteristics, was performed. The stability of the formulation in stock conditions at 4 °C and in blood biomimetic medium was established. The adsorption on Tg-NEs of peptide-22 was realized. The functionalized NEs were characterized by chromatographic methods (SEC and C18/HPLC) and isothermal titration calorimetry, attesting the efficiency of the adsorption. From in vitro assays, these nanocarriers appeared suitable for enabling tegaserod controlled release without hemolytic properties. Conclusion: The developed peptide-22 functionalized Tg-NEs appear as a valuable tool to allow exploration of the repurposed tegaserod in AD treatment in further preclinical studies.

High-throughput enzyme inhibition screening of 44 Iranian medicinal plants via piezoelectric spraying of planar cholinesterase assays

A rapid and straightforward approach was developed for screening the acetyl- and butyrylcholinesterase (ChE) inhibitory activity of 44 Iranian medicinal plant extracts at laboratory scale. After a fast ChE inhibitory pre-testing of samples applied as band pattern, 40 out of the 44 Iranian medicinal plant extracts were selected. These were adjusted in the application volume depending on their inhibition activity, applied on both plate sides and simultaneously developed in a horizontal developing chamber. Different mobile phases were studied to achieve maximum separation of ChE inhibitors and minimum co-elution with matrix. Contrary to immersion, the piezoelectric spraying reduced the consumption of assay solutions, prevented zone tailing, zone shift and cross-contamination, and homogeneously covered the entire plate surface with the assay solutions. The ChE inhibitors of the six most bioactive plant extracts were tentatively assigned by high-resolution mass spectrometry in combination with the spectral and chromatographic information obtained.

Anti-cholinergic activities of Turkish Corydalis DC. species

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.

Design, synthesis and biological evaluation of naringenin carbamate derivatives as potential multifunctional agents for the treatment of Alzheimer’s disease

A series of naringenin derivatives were designed and synthesized as multifunctional anti-Alzheimer’s disease (AD) agents. The results showed that these derivatives displayed moderate-to-good acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities at the micromolar range (IC50, 12.91 ~ 62.52 μM for AChE and 0.094 ~ 13.72 μM for BuChE). Specifically, compound 1 showed the highest inhibitory activity against BuChE with the IC50 value of (0.094 ± 0.0054) μM. A Lineweaver-Burk plot and molecular docking studies demonstrated that 1 targeted both the catalytically active site (CAS) and the peripheral anion site (PAS) of BuChE. Besides, all derivatives showed excellent hydroxyl free radicals (·OH) scavenging ability than vitamin C and cyclic voltammetry results displayed that 1 could effectively scavenge superoxide anion radical (·O2–). In addition, compound 1 displayed good metal chelating properties and had anti-Aβ aggregation activities. Therefore, compound 1 might be the potential anti-AD agent for further developments.

Synthesis, Biological Evaluation, and In Silico Studies of New Acetylcholinesterase Inhibitors Based on Quinoxaline Scaffold.

A quinoxaline scaffold exhibits various bioactivities in pharmacotherapeutic interests. In this research, twelve quinoxaline derivatives were synthesized and evaluated as new acetylcholinesterase inhibitors. We found all compounds showed potent inhibitory activity against acetylcholinesterase (AChE) with IC50 values of 0.077 to 50.080 µM, along with promising predicted drug-likeness and blood–brain barrier (BBB) permeation. In addition, potent butyrylcholinesterase (BChE) inhibitory activity with IC50 values of 14.91 to 60.95 µM was observed in some compounds. Enzyme kinetic study revealed the most potent compound (6c) as a mixed-type AChE inhibitor. No cytotoxicity from the quinoxaline derivatives was noticed in the human neuroblastoma cell line (SHSY5Y). In silico study suggested the compounds preferred the peripheral anionic site (PAS) to the catalytic anionic site (CAS), which was different from AChE inhibitors (tacrine and galanthamine). We had proposed the molecular design guided for quinoxaline derivatives targeting the PAS site. Therefore, the quinoxaline derivatives could offer the lead for the newly developed candidate as potential acetylcholinesterase inhibitors.

Determination of the Chemical Composition, Antioxidant, and Enzyme Inhibitory Activity of Onosma mollis DC

Onosma species have long been used traditionally for respiratory tract infections, abdominal pain, wound treatment, burns, and constipation. This study aims to investigate the chemical composition and in vitro antioxidant and enzyme inhibitory activities of ethyl acetate (EtOAc), methanol (MeOH), and water extracts of Onosma mollis DC. MeOH extract was richer in both phenolics and flavonoids than other extracts (44.06 mg GAEs/g and 41.57 mg QEs/g, respectively). The findings obtained from the results of the chromatographic analysis also supported the results of the spectrophotometric analysis. The MeOH extract was the richest in terms of most of the phytochemicals screened. Apigenin 7-glucoside, luteolin 7-glucoside, rosmarinic acid, vanillic acid, and pinoresinol were over 1000.0 μg/g in MeOH extract. The extract in question showed the highest activity in phosphomolybdenum, DPPH, and ABTS radical scavenging and CUPRAC and FRAP reducing power activity assays (2.01, 3.33, 2.30, 1.48, and 0.79 mg/ml, respectively). The water extract presented the highest activity in the ferrous ion chelating assay (1.01 mg/ml). While EtOAc extract showed high activity in acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase inhibitory activity tests (1.11, 1.49, and 1.07 mg/ml, respectively), MeOH extract showed significant efficacy in tyrosinase and α-amylase inhibitory activity assays (2.94 and 2.08 mg/ml, respectively). There was a high correlation between the total phenolics/flavonoids of the extracts and their antioxidant activities (correlation coefficients were over 0.9). In addition, the phytochemicals mentioned above were found to contribute significantly to the antioxidant activity. It was concluded that a more detailed analysis should be done to determine the compounds responsible for the enzyme inhibitory activities of the extracts.

Evaluation of cholinesterase inhibitory and antioxidant activity of Wedelia chinensis and isolation of apigenin as an active compound

BackgroundWedelia chinensis has been reported as a folk medicine for the treatment of different diseases including neurodegenerative disease. Although the plant has been studied well for diverse biological activities, the effect of this plant in neurological disorder is largely unknown. The present study was undertaken to evaluate the cholinesterase inhibitory and antioxidant potential of W. chinensis.MethodsThe extract and fractions of the plant were evaluated for acetylcholinesterase and butyrylcholinesterase inhibitory activity by modified Ellman method. The antioxidant activity was assessed in several in vitro models/assays such as reducing power, total antioxidant capacity, total phenolic and flavonoid content, scavenging of 2,2′-diphenyl-1-picrylhydrazyl (DPPH) free radical and hydroxyl radical, and inhibition of brain lipid peroxidation. Chromatographic and spectroscopic methods were used to isolate and identify the active compound from the extract.ResultsAmong the fractions, aqueous fraction (AQF) and ethylacetate fraction (EAF) exhibited high inhibition against acetylcholinesterase (IC50: 40.02 ± 0.16 μg/ml and 57.76 ± 0.37 μg/ml) and butyrylcholinesterase (IC50: 31.79 ± 0.18 μg/ml and 48.41 ± 0.05 μg/ml). Similarly, the EAF and AQF had high content of phenolics and flavonoids and possess strong antioxidant activity in several antioxidant assays including DPPH and hydroxyl radical scavenging, reducing power and total antioxidant activity. They effectively inhibited the peroxidation of brain lipid in vitro with IC50 values of 45.20 ± 0.10 μg/ml and 25.53 ± 0.04 μg/ml, respectively. A significant correlation was observed between total flavonoids and antioxidant and cholinesterase inhibitory activity. Activity guided chromatographic separation led to the isolation of a major active compound from the EAF and its structure was elucidated as apigenin by spectral analysis.ConclusionsThe potential ability of W. chinensis to inhibit the cholinesterase activity and peroxidation of lipids suggest that the plant might be useful for the management of AD.

Phytochemical Analysis and Evaluation of Biological Activity of Lawsonia inermis Seeds Related to Alzheimer's Disease.

Using Lawsonia inermis L. (henna) seeds has been frequently recommended for the improvement of memory in Iranian Traditional Medicine (ITM). In this respect, different fractions of the plant were prepared and evaluated for their in vitro biological assays related to Alzheimer's disease (AD), including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity as well as metal chelating ability and DPPH antioxidant activity. The dichloromethane and ethyl acetate fractions were able to inhibit the BChE selectively with IC50 values of 113.47 and 124.90 μg/mL, respectively, compared with donepezil as the reference drug (IC50 = 1.52 μg/mL). However, all fractions were inactive toward AChE. Phytochemical analysis of the dichloromethane fraction indicated the presence of β-sitosterol (1), 3-O-β-acetyloleanolic acid (2), 3-O-(Z)-coumaroyl oleanolic acid (3), betulinic acid (4), and oleanolic acid (5). The inhibitory activity of isolated compounds was also evaluated toward AChE and BChE. Among them, compounds 2 and 5 showed potent inhibitory activity toward BChE with IC50 values of 77.13 and 72.20 μM, respectively. However, all compounds were inactive toward AChE. Moreover, molecular docking study confirmed desired interactions between those compounds and the BChE active site. The ability of fractions and compounds to chelate biometals (Cu2+, Fe2+, and Zn2+) was also investigated. Finally, DPPH antioxidant assay revealed that the ethyl acetate (IC50 = 3.08 μg/mL) and methanol (IC50 = 3.64 μg/mL) fractions possessed excellent antioxidant activity in comparison to BHA as the positive control (IC50 = 3.79 μg/mL).

Amygdalus spinosissima root extract enhanced scopolamine-induced learning and memory impairment in mice.

The Amygdalus spinosissima (Rosaceae) plant has been used in the Iranian folk medicine as a remedy for the burn wound. Hence, in this study, we aimed to determine the possible medicinal potential of the plant focusing on the root part. The bioactive phenolic and flavonoid compounds present in the root extract of the Amygdalus spinosissima plant as well as its antioxidant and anti-inflammatory properties were determined. Moreover, the effects of root extract on learning and memory in mice were evaluated. The results revealed that the root methanolic extract contained phenolic and flavonoid compounds including apigenin, quercetin, rutin, kaempferol, gallic acid, syringic acid, ferulic acid, and ellagic acid. The extract possessed antioxidant, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activities in vitro. These biological activities were attributed to the presence of phenolics and flavonoids. The A. spinosissima root extract improved learning and memory function in scopolamine-induced memory dysfunction in mice as determined using the Morris water maze task. The extract modulated the AChE, BChE, and inflammatory genes and enhanced the expression of the antioxidant enzymes in the brain. Consequently, A. spinosissima root extract could be considered as a promising source of potent bioactive compounds in the retarding the development of neurodegenerative diseases such as Alzheimer's disease.