Anti-acetylcholinesterase Activity Research Articles

In Vitro and In Silico Anti-Acetylcholinesterase Activity from Macaranga tanarius and Syzygium jambos.

Macaranga tanarius (MT) and Syzygium jambos (SJ) are pharmacologically reported to have anti-oxidant, anti-inflammatory, and anti-diabetic effects, and can be neuroprotective agents. Our previous work revealed that MT and SJ exhibited 76.32% and 93.81% inhibition against acetylcholinesterase (AChE) at 50 μg/mL final concentration in their ethyl acetate and hexane fractions, respectively. This study was aimed to investigate the bioactive constituents of MT and SJ and their molecular mechanism toward AChE inhibition. Bioassay-guided isolation afforded prenylflavonoids 1–3 from MT and anacardic acid derivatives 4 and 5 from SJ that were confirmed by NMR and MS data. Compound 5 exerted the strongest anti-AChE potential (IC50: 0.54 μM), followed by 1, 4, 3, and 2 (IC50: 1.0, 2.4, 6.8, and 33 μM, respectively). In silico molecular docking revealed 5 formed stronger molecular interactions including three H-bonds than its derivative 4 based on the saturation of their alkyl chains. The addition of a five carbon-prenyl chain in 1 increased the number of binding interactions, justifying its greater activity than derivatives 2 and 3. This research reflects the first report of AChE inhibitors from these species, thereby adding pharmacological values to MT and SJ as potential remedies in neuroprotection.

Phenolic Composition, In-vitro Antioxidant and Enzyme Inhibition Activities of Cardaria draba Different Parts

The plant Cardaria draba (L.) Desv. subsp. draba (Brassicaceae), is traditionally used for various ailments in different cultures. We investigated different solvent extracts such as methanol, ethanol, and water extracts obtained from flowers, leaves, stems, and roots of C. draba for their chemical composition, as well as antioxidant and enzyme inhibition activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase, α-amylase, and tyrosinase). RP-HPLC technique was used to determine the phenolic profile of each extracts. The antioxidant activities of the extracts were determined by using DPPH and ABTS method, total phenol and flavonoid content analysis, and iron chelating assay. Enzyme inhibitory potential was evaluated by 96-microplate method. According to the results, aqueous extract of flower demonstrated the highest total phenolic content (64.32 µgGAE/ mg), while leaf ethanol extract showed the highest total flavonoid content (141.47 µgQE/ mg) among all extracts. The methanol, and water extracts of flowers were the most effective DPPH scavenger while aqueous extract of flower was the most active on ABTS scavenging. It is shown that the extracts possess promising activity against α-glucosidase than α-amylase enzyme. The methanolic extract of flower showed anti-acetylcholinesterase activity, and the ethanolic extract of the stem exhibited the best anti-butyrylcholinesterase activity among the 12 extracts. As for the anti-tyrosinase activity, higher kojic acid equivalent values were found for the aqueous extracts of roots and leaves. In conclusion, the data obtained from this study may serve as the basis for the bioassay-guided isolation of active compounds and the development of novel drugs from Cardaria draba.

Exploration of essential oil from Psychotria poeppigiana as an anti-hyperalgesic and anti-acetylcholinesterase agent: Chemical composition, biological activity and molecular docking

Ethnopharmacological relevanceLeaves from Psychotria poeppigiana Müll. Arg. (accepted as Palicourea tomentosa (Aubl.) Borhidi), Rubiaceae, has traditionally been used in medicine for treatments of inflammation and pain; Synonymously, Cephaelis elata for the treatment of dementia; However, few scientific studies have been evidence demonstrating this activity. Aim of the studyThe aim of this study was to investigate the chemical composition of P. poeppigiana essential oil obtained from leaves (EOPP) and its antioxidant, anti-inflammatory and acetylcholinesterase (AChE) activities. Molecular docking simulations were carried out with the main constituents. Materials and methodsEOPP (hydrodistillation) was analysed by gas chromatography-mass spectrometry (GC–MS). The fractionation of EOPP afforded germacrene D and bicyclogermacrene. The antioxidant activity of EOPP was determined by MDA assay. The inflammatory parameters were evaluated using CFA model (with paw edema, mechanical, thermal hyperalgesia, MPO and NAG) in EOPP (30, 100 and 300 mg/kg), germacrene D and bicyclogermacrene (30 mg/kg). The AChE inhibition was evaluated in rat brain structures and molecular docking simulations were carried out using Autodock v.4.3.2. ResultsGC-MS analysis identified 19 compounds, and the major compounds were germacrene D (29.38%) and bicyclogermacrene (25.21%). EOPP exhibited high antioxidant capacity (IC50 = 12.78 ± 1.36 μg/mL). All the tested doses of EOPP and both major constituents significantly inhibited cold and mechanical hyperalgesia and significantly blocked the increase in MPO activity 24 h after the CFA injection. There was significant AChE inhibition by EOPP and germacrene D in the cerebral cortex and hippocampus (>50%). Enzyme-ligand molecular modelling showed that the major constituents of EOPP interacted differently with AChE. ConclusionsThe chemical compounds of the essential oil from the leaves of P. poeppigiana is based mainly on terpenes, the sesquiterpenes germacrene D (29.38%) and bicyclogermacrene (25.21%) being the major compounds. EOPP presented antioxidant, anti-inflammatory and anti-acetylcholinesterase (AChE) activities. Besides, enzyme-ligand molecular modelling showed the EOPP may act as an anti-hyperalgesic and AChE inhibitory agent. Taken together, these results might be in accordance with if folk use for pain- and inflammation-related symptoms.

Baoshanmycin and a New Furanone Derivative from a Soil-Derived Actinomycete, Amycolatopsis sp. YNNP 00208.

Actinomycetes have being regarded as a treasure reservoir of various bioactive secondary metabolites and devoted many antibiotics in clinicals. Amycolatopsis sp. YNNP 00208 was isolated from a soil sample collected in Gaoligong Mountain area, Yunnan Province, China. Chemical investigation of its fermentation broth led to a new amide, baoshanmycin (1), and a new furanone derivative, 3-(1,3-dihydroxybutyl)-4-methylfuran-2(H)-one (2), together with eight known compounds, including two amides (3-4), four cyclic dipeptides (5-8), and two deoxyribonucleosides (9-10). Their structures were established on basis of the 1D- and 2D-NMR spectroscopic data, along with the HR-ESI-MS experiments. Baoshanmycin (1) showed moderate antimicrobial activities against Candida albicans, and weak activities against Staphylococcus aureus, multi-drug resistant Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes, fluconazole-resistant Candida albicans. Baoshanmycin (1) presented strong antioxidant activity and moderate anti-acetylcholinesterase activity. The other compound 3-(1,3-dihydroxybutyl)-4-methylfuran-2(H)-one (2) and the known compounds (3-10) showed moderate antioxidant activity.

In vitro studies of a series of synthetic compounds for their anti-acetylcholinesterase activities identified arylpyrano[2,3-f]coumarins as hit compounds

Alzheimer's disease is one of the most widespread neurodegenerative diseases in the world. Until now, the drugs used to control this disease have been developed to target acetylcholinesterase (AChE). With the aim to identify new pharmacophores that can promisingly inhibit this enzyme, a library of 72 compounds belonging to chalcones, pyranochromenes, chromenes, pyranopyrazoles and dihydropyridines, was evaluated against AChE. Nineteen of these compounds are newly reported and among the tested compounds, seven, bearing a pyranochromene skeleton, showed inhibitory effects with IC50 values ranging from 9.01 to 32.39 µM. The most potent was identified as 8-amino-10-(4-bromophenyl)-5‑hydroxy-4-methyl-2-oxo-2,10-dihydropyrano[2,3-f]chromeno-9-carbonitrile. In silico studies using human recombinant acetylcholinesterase (PDB: 4EY7) showed important proximities between the NH2 group of this compound and E202 in AChE, between W86 and the OH-5 group, between W86 and the aromatic bicyclic system (π-π stacking, 4.2 Å), and between Y133 and both the OH-7 and the NH2 groups. These pyranochromenes emerged as a promising prototype for the development of new candidates against AChE.

The Insight of In Silico and In Vitro evaluation of Beta vulgaris phytochemicals against Alzheimer's disease targeting acetylcholinesterase.

B. vulgaris extracts possess antioxidant, anti-inflammatory along with its role in improving memory disorders. Subsequently, in vitro and in silico studies of its purified phytochemicals may expand complementary and alternative Alzheimer’s therapeutic option. Super activation of acetylcholinesterase enzyme is associated explicitly with Alzheimer’s disease (AD) ultimately resulting in senile dementia. Hence, acetylcholinesterase enzyme inhibition is employed as a promising approach for AD treatment. Many FDA approved drugs are unable to cure the disease progression completely. The Present study was devised to explore the potential bioactive phytochemicals of B. vulgaris as alternative therapeutic agents against AD by conducting in vitro and in silico studies. To achieve this, chemical structures of phytochemicals were recruited from PubChem. Further, these compounds were analyzed for their binding affinities towards acetylcholinesterase (AChE) enzyme. Pharmacophoric ligand-based models showed major characteristics like, HBA, HBD, hydrophobicity, aromaticity and positively ionizable surface morphology for receptor binding. Virtual screening identified three hit compounds including betanin, myricetin and folic acid with least binding score compared to the reference drug, donepezil (-17 kcal/mol). Further, in vitro studies for anti-acetylcholinesterase activity of betanin and glycine betaine were performed. Dose response analysis showed 1.271 μM and 1.203 μM 50% inhibitory concentration (IC50) values for betanin and glycine betaine compounds respectively. Our findings indicate that phytoconstituents of B. vulgaris can be implicated as an alternative therapeutic drug candidate for cognitive disorders like Alzheimer’s disease.

Comparative Antioxidant, Anti-Acetylcholinesterase and Anti-α-Glucosidase Activities of Mediterranean Salvia Species.

Salvia species have a cosmopolitan distribution and comprise several well-known plants valuable for pharmaceutical and food industries due to their recognized medicinal, food flavouring, and preservative properties. The present study aimed to evaluate and compare the biological activities of seven wild-growing Salvia species from the Mediterranean area (S. fruticosa, S. glutinosa, S. nemorosa, S. officinalis, S. pratensis, S. sclarea, S. verticillata). All studied ethanolic leaf extracts exhibited significant DPPH and NO radical scavenging ability, lipid peroxidation inhibition, and reducing power, as well as moderate iron-chelating properties. Together with S. officinalis and S. fruticosa, S. verticillata showed anti-acetylcholinesterase activity, while S. glutinosa was also found to possess the ability to inhibit α-glucosidase. Total flavonoid (0.37–0.90%), phenolic acid (3.55–12.44%), tannin (1.22–2.60%), and anthocyanin contents (0.03–0.08%) were determined in Salvia leaves. Rosmarinic acid was the predominant hydroxycinnamic acid in all studied sage plants, ranging from 9400 to 38,800 μg/g. The correlation study showed a strong relationship between biological activities and contents of total phenolic acids, total tannins, and rosmarinic acid, indicating their significant contribution to the efficiency of tested Salvia species. Our results highlighted Mediterranean sage plants as rich sources of potent antioxidant, neuroprotective, and hypoglycemic agents which are worthy of further research.

Asperbenzophenone A and Versicolamide C, New Fungal Metabolites from the Soft Coral Derived Aspergillus sp. SCSIO 41036.

Two new compounds, asperbenzophenone A (1) and versicolamide C (5), together with fifteen known compounds were isolated from a soft coral derived fungus Aspergillus sp. SCSIO 41036. Their structures were elucidated by spectroscopic methods, ECD analysis, and by a comparison with data from the literature. In bioassay, compound 8 showed significant inhibitory activity against lipopolysaccharide-inducted nitric oxide (NO) in RAW264.7 cells at the concentration of 10 μM. Additionally, the anti-acetylcholinesterase activity assay showed that 14 exhibited weak inhibition with an IC50 value of 157.8 μM.

Comparison of Various Solvent Extracts and Major Bioactive Components from Unsalt-Fried and Salt-Fried Rhizomes of Anemarrhena asphodeloides for Antioxidant, Anti-α-Glucosidase, and Anti-Acetylcholinesterase Activities.

The rhizome of Anemarrhena asphodeloides Bunge (AA, family Liliaceae) is a famous and frequently used herbal drug in the traditional medicine of Northeast Asia, under vernacular name “zhimu”. A. asphodeloides has been used as an anti-inflammatory, antipyretic, anti-platelet aggregation, anti-depressant, and anti-diabetic agent in traditional Chinese medicine. We examined the antioxidant, anti-acetylcholinesterase (AChE), and anti-α-glucosidase activities of various solvent extracts and the main bioactive compounds from the rhizome of A. asphodeloides. Acetone extract exhibited comparatively high antioxidant activities by 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, and ferric-reducing antioxidant power (FRAP) assays. A water extract exhibited relatively strong antioxidant activity by superoxide radical scavenging test. Furthermore, dichloromethane, chloroform, and n-hexane extracts showed significant anti-α-glucosidase activities. Finally, ethanol and dichloromethane extracts exhibited relatively strong AChE inhibitory activity. HPLC analysis was used to examine and compare various solvent extracts for their compositions of isolates. We isolated four major chemical constituents and analyzed their antioxidant, anti-α-glucosidase, and AChE inhibitory activities. The bioactivity assays showed that mangiferin displayed the most potential antioxidant activities via FRAP, ABTS, DPPH, and superoxide assays and also exhibited the most effective anti-AChE and anti-α-glucosidase activities among all the isolates. The present study suggests that A. asphodeloides and its active extracts and components are worth further investigation and might be expected to develop as a candidate for the treatment or prevention of oxidative stress-related diseases, AChE inhibition, and hyperglycemia.

Phenolic composition, antioxidant and antiacetylcholinesterase activities of Opuntia ficus‐indica peel and flower teas after in vitro gastrointestinal digestion

The flowers and peels of cactus Opuntia ficus-indica (OFI) are by-products generally discarded. Their beneficial properties have been linked to the chemical composition without taking into account its transformations during digestion. This study evaluated and compared the phenolic composition, antioxidant and antiacetylcholinesterase activities of OFI peel and flower teas before and after in vitro gastrointestinal digestion. Results showed that OFI peel tea was a source of natural phenolic compounds and carotenoids, while OFI flower tea was a source of flavonoids. Both OFI peel and flower teas exhibited high antioxidant activities (AAs) measured by several tests [1,1-diphenyl-2-picrylhydrazyl radical (DPPH• ), reducing power (RP), hydrogen peroxide scavenging activity (HPSA)]. Flower teas presented a higher antiacetylcholinesterase inhibition percentage than peel teas. Significant decreases of acetylcholinesterase and AAs were obtained under in vitro gastrointestinal digestion. Fourteen phenolic compounds typical of phenolic acids and flavonoids were identified in both teas. These compounds seemed to be more affected by pancreatic than by the gastric conditions. OFI peel tea has been found as a source of natural phenolic compounds and carotenoids, while OFI dry flower tea as a source of flavonoids. The OFI flower tea phytochemicals were more stable than peel tea during the digestive process. These findings suggest that peels and flowers of OFI should be considered as sources of healthy ingredients. © 2022 Society of Chemical Industry.

Cholinesterase inhibitory activities of neuroprotective fraction derived from red alga Gracilaria manilaensis

Anti-cholinesterase (ChE)s are commonly prescribed as the symptomatic treatment of Alzheimer’s disease. They are applied to prevent the breakdown of neurotransmitter acetylcholine (ACh) that bind to muscarinic and nicotinic receptors in the synaptic cleft. Seaweeds are one of the richest sources of bioactive compounds for both nutraceuticals and pharmacognosy applications. This study aimed to determine the anti-ChEs activity of Gracilaria manilaensis, one of the red seaweeds notables for its economic importance as food and raw materials for agar production. Methanol extracts (GMM) of G. manilaensis were prepared through maceration, and further purified with column chromatography into a semi-pure fraction. Ellman assay was carried out to determine the anti-acetylcholinesterase (AChE) and anti-butyrylcholinesterase (BuChE) activities of extracts and fractions. Lineweaver-Burk plot analysis was carried out to determine the inhibition kinetic of potent extract and fraction. Major compound(s) from the most potent fraction was determined by liquid chromatography-mass spectrometry (LCMS). GMM and fraction G (GMMG) showed significant inhibitory activity AChE with EC50 of 2.6 mg/mL and 2.3 mg/mL respectively. GMM and GMMG exhibit mixed-inhibition and uncompetitive inhibition respectively against AChE. GMMG possesses neuroprotective compounds such as cynerine A, graveolinine, militarinone A, eplerenone and curumenol. These findings showed a promising insight of G. manilaensis to be served as a nutraceutical for neuronal health care in the future.

Inhibition of α-Glucosidase, Acetylcholinesterase, and Nitric Oxide Production by Phytochemicals Isolated from Millettia speciosa-In Vitro and Molecular Docking Studies.

The phytochemical constituents from the roots of Millettia speciosa were investigated by chromatographic isolation, and their chemical structures were characterized using the MS and NMR spectroscopic methods. A total of 10 compounds, including six triterpenoids, two flavonoids, and two phenolic compounds, were identified from the roots of M. speciosa. Out of the isolated compounds, eight showed inhibitory effects on NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, with IC50 values ranging from 43.9 to 449.5 µg/mL. Ursane-type triterpenes significantly suppressed NO production compared to the remaining compounds. In addition, these compounds also exhibited remarkable inhibitory effects on α-glucosidase. Among the tested compounds, 4, 5, and 10 exhibited excellent α-glucosidase inhibition, with IC50 values ranging from 1.1 to 2.2 µg/mL. Almost all of the test compounds showed little or no acetylcholinesterase inhibition, except for 5, which showed moderate anti-acetylcholinesterase activity in vitro. The molecular docking study of α-glucosidase inhibition by 3–5 and 10 was conducted to observe the interactions of these molecules with the enzyme. Compounds 4, 5, and 10 exhibited a better binding affinity toward the targeted receptor and the H-bond interactions located at the entrance of the enzyme active site pocket in comparison to those of 3 and the positive control acarbose. Our findings evidence the pharmacological potential of this species and suggest that the phytochemicals derived from the roots of M. speciosa may be promising lead molecules for further studies on the development of anti-inflammatory and anti-diabetes drugs.

Anti-acetylcholinesterase activity of Corallocarpus epigaeus tuber: In vitro kinetics, in silico docking and molecular dynamics analysis

Biological activities of Corallocarpus epigaeus tuber (CET) were determined and its active constituents were identified. CET was sequentially extracted with various solvents. The methanol extract was further fractionated using silica coloumn chromatography to obtain active constituents-rich fraction called CET-MAF. The phytochemicals in CET-MAF was identified using GC-MS analysis. The in vitro antioxidant activity and inhibition against various globular forms of acetylcholinesterase (AChE) by CET-MAF were determined. In silico analysis of CET-MAF active constituents interaction with human AChE was carried out. CET-MAF showed in vitro antioxidant activity. CET-MAF inhibited various globular forms of AChE, G1 (IC50 = 147 µg/ml; Ki=13.6 µg/ml), G2 (IC50=146 µg/ml; Ki=8.6 µg/ml) and G4 (IC50 = 158 µg/ml; Ki = 9.3 µg/ml) in mixed manner. Molecular docking analysis revealed the interaction of active constituents such as 5-acetoxypentadecane (5AP) and alpha-linolenic acid (ALA) of CET-MAF with active site of AChE. Molecular dynamics simulation for 500 ns revealed the stable binding of these compounds with AChE. MMBGSA calculation revealed the binding energy of -52.95 and -55.49 kcal/mol for interaction of ALA and 5AP with AChE, respectively. Altogether, CET-MAF showed biological activities in vitro which can be used against cognitive dysfunction.

Antilipase, antiacetylcholinesterase and antioxidant activities of Moringa oleifera extracts

Pancreatic lipase is critical for the catabolism of lipids in the intestine, making it a prime target for obesity management. Acetylcholinesterase is an important enzyme that hydrolyses the neurotransmitter acetylcholine. It inhibition is paramount in enhancing systemic acetylcholine level. Side effects of conventional drugs lead to continued search for alternative anti-obesity and anticholinesterase agents. The present study assessed lipase and acetylcholinesterase inhibition, as well as antioxidant activity of Moringa oleifera extracts. The inhibitory activities of the extracts on lipase and acetylcholinesterase were dose dependent. Aqueous leaf extract (IC50 = 3.26 ± 0.26 mg/ml) and hexane root extract (IC50 = 0.08 ± 0.00 mg/ml) exhibited the highest antilipase and antiacetylcholinesterase activity respectively. Aqueous extracts of root and leaf (IC50 of 1.43 ± 0.03mg/ml and 1.86 ± 0.10 mg/ml respectively) had the highest N, N-dimethyl-p-phenylene diamine dihydrochloride radical scavenging activity, while ethyl acetate leaf extract had the highest nitrite scavenging activity (IC50 = 2.20 ± 0.06 mg/ml). Compared to other extracts, methanol leaf extract exhibited the highest ferric reducing power. These findings suggest that M. oleifera possess promising antilipase, antiacetylcholinesterase and antioxidant potentials. Therefore, may be employed as food additive for the management of obesity, Alzheimer and other degenerative diseases.

Essential oils from different Citrus species and evaluation of their in vitro antibacterial, antiacetylcholinesterase, anti-inflammatory and antifungal activities

Essential oils (EOs) from Citrus are not only economic, eco-friendly and natural alternatives to chemical preservatives but also have other biological applications. This study aimed to investigate the chemical composition of Citrus species (EOs from C. limonia, C. latifolia, C. sinensis and C. deliciosa fruit peel) to evaluate their in vitro antibacterial activity against Listeria monocytogenes, Yersinia enterocolitica, Staphylococcus aureus, Clostridium botulinum and Bacillus cereus. The chemotaxis model, which was used for evaluating their anti-inflammatory activity, showed that EOs exhibited effective results when the dose was 100 µg/mL. Regarding all antimicrobial activities, minimum inhibitory concentration (MIC) values of EOs were calculated by the broth microdilution method on 96-well microplates. EOs showed satisfactory antifungal activity against Malassezia furfur (MIC values between 32.5 and 62.5 µg/mL). Citrus deliciosa, whose MIC = 95.8 µg/mL, inhibited acetylcholinesterase (AChE) more selectively. All EOs from Citrus spp. fruit peel showed good antibacterial activity against Yersinia enterocolitica (MIC = 62.5 µg/mL) and Staphylococcus aureus (MIC = 62.5 µg/mL), mainly the EO from C. deliciosa whose MIC values were 50 µg/mL for both. EOs were moderately active against Clostridium botulinum, Bacillus cereus and Listeria monocytogenes since MIC values ranged from 100 μg/mL to 400 μg/mL. Both GC-FID and GC-MS analyses revealed that the single major constituent determined in EOs is the terpene limonene. EOs from Citrus may be important active ingredients of several products to prevent bacterial growth in food, to attack the fungus that causes seborrheic dermatitis and to treat inflammatory processes. In short, the promising antiacetylcholinesterase activity of EOs under evaluation was attributed to the high concentration of the monoterpene limonene

Extracts of the Native Brazilian Tree Garcinia gardneriana Inhibit Urediniospore Germination of Coffee Leaf Rust Fungus

The fungal Hemileia vastatrix is the causal agent of coffee leaf rust, one of the worst and devastating disease in coffee cultures worldwide. As a result of our research on natural products for the development of novel agrochemicals, we found that the hexane extract from leaves of the Brazilian medicinal plant Garcinia gardneriana, at 500 μg mL–1, inhibited in 98% the germination of H. vastatrix urediniospores. This extract showed no phytotoxicity when tested for seed germination and seedling growth inhibitory activity using sensible plant species. Also, the hexane extract from leaves was tested for anti-acetylcholinesterase activity, which constitutes a mechanism of action of major commercial insecticides used in agriculture, and showed low activity even at concentrations about two times higher than the half maximal inhibitory concentration (IC50) found in the antifungal assays. Gas chromatography-mass spectrometry (GC-MS) analysis showed that the hexane extract is constituted mainly by the pentacyclic triterpene lupeol, together with a series of sesquiterpenes as minor components. This is the first report on the investigation of antifungal, phytotoxic and acetylcholinesterase activities of extracts from leaves of G. gardneriana. These findings indicate that G. gardneriana may constitute a promising source of natural products for controlling the coffee leaf rust fungus.

Phenolic Content, Antioxidant, Antibacterial, and Anti-Acetylcholinesterase Activities of Biosynthesized and Characterized Silver Nanoparticles from Tunisian Medicinal Lichen Species.

Lichens produce a myriad of bioactive compounds that can be exploited as reducing and capping agents in the green process of synthesizing nanoparticles. In this study, we exploit a simple, environmentally safe method for synthesizing silver nanoparticles (AgNPs), using aqueous extracts of three lichen species (Lobaria pulmonaria, Ramalina farinacea, and Evernia prunastri) for the first time. Characterization showed that the three lichen species selected could be perfectly suitable as reducing agents to produce AgNPs. First, ultraviolet-visible spectroscopy confirmed the presence of metallic silver with a maximum absorbance at 425 nm. Second, Fourier transform infrared spectroscopy analysis confirmed the chemical compounds involved in reduction. Third, the elemental composition of AgNPs was illustrated by energy dispersive X-ray spectroscopy. Finally, scanning electron microscopy images displayed the size and shape of biosynthesized particles. The prepared extracts containing AgNPs showed high contents of phenolic compounds and high antioxidant activities on three assays (DPPH, ferric reducing power, and chelating power). Moreover, since bacteria are developing resistance to many common antibiotics, AgNPs produced in an environmentally safe method are an interesting replacement. The antibacterial assessment revealed more effective activity against Gram-negative than Gram-positive bacteria and a bactericidal effect against all strains tested. In this study, we present a pioneering evaluation of acetylcholinesterase inhibition by lichen-based AgNPs. The three extracts exhibited strong enzyme inhibition, with IC50 values of 3.46 ± 0.09, 3.59 ± 0.02, and 4.34 ± 0.03 mg/mL for L. pulmonaria, R. farinacea, and E. prunastri, respectively. The green approach presented would encourage the nontoxic production of AgNPs, suggesting pharmaceutical applications.

Discovery of novel β-carboline derivatives as selective AChE inhibitors with GSK-3β inhibitory property for the treatment of Alzheimer's disease

The natural product harmine, a representative β-carboline alkaloid from the seeds of Peganum harmala L. (Zygophyllaceae), possesses a broad spectrum of biological activities. In this study, a novel series of harmine derivatives containing N-benzylpiperidine moiety were identified for the treatment of Alzheimer's disease (AD). The results showed that all the derivatives possessed significant anti-acetylcholinesterase (AChE) activity and good selectivity over butyrylcholinesterase (BChE). In particular, compound ZLWH-23 exhibited potent anti-AChE activity (IC50 = 0.27 μM) and selective BChE inhibition (IC50 = 20.82 μM), as well as acceptable glycogen synthase kinase-3 (GSK-3β) inhibition (IC50 = 6.78 μM). Molecular docking studies and molecular dynamics simulations indicated that ZLWH-23 could form stable interaction with AChE and GSK-3β. Gratifyingly, ZLWH-23 exhibited good selectivity for GSK-3β over multi-kinases and very low cytotoxicity towards SH-SY5Y, HEK-293T, HL-7702, and HepG2 cell lines. Importantly, ZLWH-23 displayed efficient reduction against tau hyperphosphorylation on Ser-396 site in Tau (P301L) 293T cell model. Collectively, harmine-based derivatives could be considered as possible drug leads for the development of AD therapies.

Pharmacological Evaluation of Green Chilli in Alzheimer’s Disease

Pharmacognosy Research,2022,14,1,61-70.DOI:10.5530/pres.14.1.10Published:December 2021Type:Research ArticleAuthors:Pandurangan Perumal, and Desmond Yong Hua Chong Author(s) affiliations:Pandurangan Perumal1,*Desmond Yong Hua Chong2 1Department of Pharmaceutical Analysis, Sree Vidyanikethan College of Pharmacy, Tirupathi, Andrapradesh, INDIA. 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Asian Institute of Medicine Science Technology (AIMST ) University, Bedong, Kedah DarulAman, MALAYSIA. Abstract:Background: Green chilli pepper (Capsicum annum L. car frutescens) is popular as a spice used in many cuisines across the world. Capsaicin, as the pharmacologically active composition of chilli pepper, has been shown to possess antioxidant, local analgesic, and hypoglycemic effects according to many studies conducted on the red chilli pepper. However, there is no data associated with the role of green chilli peppers in Alzheimer’s disease (AD) caused by capsaicin, rather than red chilli peppers. Objectives: To evaluate the acetylcholinesterase (AChE) and beta-secretase enzyme inhibition of ethanolic extract of Capsicum frutescens (EECF) or known as green chilli in in-vitro manner. Materials and Methods: Extraction was carried out on the fruits of Capsicum frutescens with ethanol. Its ethanolic extract in different concentrations was applied as the analyte to test its anti-acetylcholinesterase activity and enzymatic inhibitory action on the beta-secretase. Donepezil with various concentrations was also prepared as the control set for comparison of effect with EECF. Both the analytes were tested using the QuantiChromTM and BACE-1 FRET assay kits, for evaluation of inhibition activity against acetylcholinesterase and BACE-1 respectively. Results: There is significant increase in the percentage of inhibition against acetylcholinesterase and BACE-1 when tested with increased concentration of EECF. Compared to inhibitory effects by EECF, donepezil exhibited higher values of IC50 against both the assayed key enzymes, though also demonstrated vital inhibitory actions in both assays. EECF also showed higher potency in controlling AD progression in terms of inhibition against acetylcholinesterase, shown by IC50 value for the acetylcholinesterase, if compared to IC50 value for BACE-1. Conclusion: Green chilli or EECF has potential to have inhibitory action on acetylcholinesterase and beta-secretase enzymes in patients with AD, but limited to optimum concentration or dose. Keywords:Acetylcholinesterase, Alzheimer’s disease, Betasecretase, Capsaicin., Green chilliView:PDF (344.54 KB) Full Text

In Silico Design of Dual-Binding Site Anti-Cholinesterase Phytochemical Heterodimers as Treatment Options for Alzheimer’s Disease

The number of patients with neurodegenerative diseases, particularly Alzheimer’s disease (AD), continues to grow yearly. Cholinesterase inhibitors (ChEIs) represent the first-line symptomatic drug treatment for mild-to-moderate AD; however, there is an unmet need to produce ChEIs with improved efficacy and reduced side effects. Herein, phytochemicals with reported anti-acetylcholinesterase (AChE) activity were ranked in silico for their anti-AChE potential. Ligands with a similar or higher binding affinity to AChE than galantamine were then selected for the design of novel dual-binding site heterodimeric drugs. In silico molecular docking of heterodimers with the target enzymes, AChE and butyrylcholinesterase (BuChE), were performed, and anti-cholinesterase binding affinities were compared with donepezil. Drug-likeliness properties and toxicity of the heterodimers were assessed using the SwissADME and ProTox-II webservers. Nine phytochemicals displayed similar or higher binding affinities to AChE than galantamine: sanguinarine > huperzine A > chelerythrine > yohimbine > berberine > berberastine > naringenin > akuammicine > carvone. Eleven heterodimeric ligands were designed with phytochemicals separated by four- or five-carbon alkyl-linkers. All heterodimers were theoretically potent AChE and BuChE dual-binding site inhibitors, with the highest affinity achieved with huperzine-4C-naringenin, which displayed 34% and 26% improved affinity to AChE and BuChE, respectively, then the potent ChEI drug, donepezil. Computational pharmacokinetic and pharmacodynamic screening suggested that phytochemical heterodimers would display useful gastrointestinal absorption and with relatively low predicted toxicity. Collectively, the present study suggests that phytochemicals could be garnered for the provision of novel ChEIs with enhanced drug efficacy and low toxicity.