Acetylcholinesterase Inhibitory Activity Research Articles

New nor-lignans from the leaves of styrax annamensis guillaumin.

Phytochemical study of the leaves of Styrax annamensis Guillaumin resulted in the isolation of a new natural product egonol-3''-sulphate (1), and two new derivatives egonol-3-methyl-D-galactopyranoside (2) and 7-methoxy-2-(3',4'-methylenedioxyphenyl)-benzofuran-5-carboxamide (3). Their chemical structures were -elucidated by spectroscopic data. Compounds 1 and 3 significantly established a great role for the chemotaxonomic aspect. Compound 1 showed cytotoxicity against four cancer cell lines KB, HepG2, Lu, and MCF7 with the IC50 values of 84.90-101.69 µg/mL, and exhibited acetylcholinesterase (AChE) inhibitory activity with the IC50 value of 97.08 µg/mL.

Potential antioxidant, α-glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of major constituents isolated from Alpinia officinarum hance rhizomes: computational studies and in vitro validation.

Alpinia officinarum is a commonly used spice with proven folk uses in various traditional medicines. In the current study, six compounds were isolated from its rhizomes, compounds 1-3 were identified as diarylheptanoids, while 4-6 were identified as flavonoids and phenolic acids. The isolated compounds were subjected to virtual screening against α-glucosidase, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) enzymes to evaluate their potential antidiabetic and anti-Alzheimer's activities. Molecular docking and dynamics studies revealed that 3 exhibited a strong binding affinity to human a α- glucosidase crystal structure compared to acarbose. Furthermore, 2 and 5 demonstrated high potency against AChE. The virtual screening results were further supported by in vitro assays, which assessed the compounds' effects on α-glucosidase, cholinesterases, and their antioxidant activities. 5-Hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenylheptan-3-one (2) showed potent antioxidant effect in both ABTs and ORAC assays, while p-hydroxy cinnamic acid (6) was the most potent in the ORAC assay. In contrary, kaempferide (4) and galangin (5) showed the most potent effect in metal chelation assay. 5-Hydroxy-1,7-diphenylhepta-4,6-dien-3-one (3) and 6 revealed the most potent effect as α-glucosidase inhibitors where compound 3 showed more potent effect compared to acarbose. Galangin (5) revealed a higher selectivity to BChE, while 2 showed the most potent activity to (AChE).

A Computational Study of Phenothiazine Derivatives as Acetylcholinesterase Inhibitors Targeting Alzheimer's Disease.

Alzheimer's disease is a neurodegenerative disorder that affects learning, memory and behavioral turbulence in elderly patients. Acetylcholinesterase (AChE) inhibitors act as anti-Alzheimer's agents. Phenothiazine derivatives are considered momentous anti-Alzheimer's agents because of their AChE inhibitory activity. The elevated levels and increased expression of this protein have been associated with Alzheimer's disease. Coumarin-fused phenothiazines have emerged as significant anti-Alzheimer's agents due to their notable receptor inhibitory activity. Some unique phenothiazine analogs were designed, and computational studies were conducted to explore their inhibitory activity against the AChE enzyme (PDB id: 4EY7) by using the Schrodinger suite-2019-4. Docking studies were conducted by using the Glide module; binding free energies were calculated by means of the Prime MM-GBSA module, and Molecular dynamics (MD) simulation was performed by using the Desmond module of the Schrodinger suite. Glide scores were used to find out the binding affinity of the ligands with the target 4EY7. The compounds exhibited enhanced hydrophobic interactions and formed hydrogen bonds, effectively impeding Acetylcholinesterase. The Glide scores for the compounds ranged from -13.4237 to -8.43439, surpassing the standard (Donepezil) with a score of -16.9898. Interestingly, a positive value was obtained for the MM-GBSA binding of the potent inhibitor. To gain insights into the dynamic behavior of the protein A8, molecular dynamics (MD) simulations were employed. Based on the results, the study concludes that phenothiazine derivatives show promise as acetylcholinesterase inhibitors. Compounds with notable Glide scores are poised to exhibit significant anti-Alzheimer's activity, suggesting their potential therapeutic efficacy. Further in vitro and in vivo investigations are warranted to validate and explore the therapeutic potentials of these compounds.

Bioactive Alkaloids from the Mangrove-Derived Fungus Nigrospora oryzae SYSU-MS0024

Chemical investigation of marine fungus Nigrospora oryzae SYSU-MS0024 cultured on solid-rice medium led to the isolation of three new alkaloids, including a pair of epimers, nigrosporines A (1) and B (2), and a pair of enantiomers, (+)-nigrosporine C (+)-3, and (−)-nigrosporine C (−)-3, together with eight known compounds (4–11). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses and compared with data in the literature. The absolute configurations of compounds 1–3 were determined by a combination of electronic circular dichroism (ECD) calculations, Mosher’s method, and X-ray single-crystal diffraction technique using Cu Kα radiation. In bioassays, compound 2 exhibited moderate inhibition on NO accumulation induced by lipopolysaccharide (LPS) on BV-2 cells in a dose-dependent manner at 20, 50, and 100 μmol/L and without cytotoxicity in a concentration of 100.0 μmol/L. Moreover, compound 2 also showed moderate acetylcholinesterase (AChE) inhibitory activities with IC50 values of 103.7 μmol/L. Compound 5 exhibited moderate antioxidant activity with EC50 values of 167.0 μmol/L.

De novo transcriptome analysis of Protohermes xanthodes Navás (Megaloptera: Corydalidae) reveling the effects of sublethal chlorpyrifos on the expression of cholinergic neuronal genes

The insect cholinergic neuron system is the target for various pesticides, including organophosphate, carbamate and neonicotinoid pesticides. In this study, we conducted a de novo transcriptome analysis on the aquatic insect Protohermes xanthodes and identified for the first time presenting sixteen genes encoding cholinergic neuronal proteins (PxanChaT, PxanVAChT, PxanmAChR, PxannAChRs, and PxanAChEs), which are candidates for acetylcholine synthesis, transport, reception and degradation in cholinergic synapse. FPKM analysis revealed that these genes are primarily expressed in head and nerve cord of P. xanthodes larvae, and some of them are also abundant in hindgut, malpighian tubules and tracheae. After exposed to different concentrations of sublethal chlorpyrifos (CPF), expression of these cholinergic neuronal genes are generally increased and then decreased with the increase of CPF concentration, except PxannAChRα9 which is increased in both 4.2 and 8.4 μg/L CPF groups. Short-term (96 h) CPF exposure resulted in significant up-regulation of PxanAChE1 expression in P. xanthodes larvae exposed to 0.42 and 4.2 μg/L CPF concentrations, while PxanAChE2 was up-regulated only in 0.42 μg/L CPF group. After long-term (14 d) CPF exposure, PxanAChE1 expression was down-regulated in 0.168 and 0.42 μg/L CPF groups. PxanAChE2 expression was dramatically decreased in all CPF groups. Moreover, acetylcholinesterase (AChE) activity was significantly decreased across all long-term CPF exposure groups. These results suggested that sublethal exposure to CPF can disrupt the expression of cholinergic neuronal genes in P. xanthodes larvae, and implied that long-term sublethal CPF exposure may cause toxic effects on P. xanthodes larvae by inhibiting AChE activity. Furthermore, identification of cholinergic neuronal genes in P. xanthodes provided candidate molecular markers for study the toxic effects of environmental pollutants on the neuron system of an aquatic predatory insect with ecological importance.

A novel source of biologically active compounds – The leaves of Serbian herbaceous peonies

In order to gain further insight into how various extraction techniques (maceration, microwave-, and ultrasound-assisted extractions) affect the chemical profile and biological activities of leaf extracts from Paeonia tenuifolia L., Paeonia peregrina Mill., and Paeonia officinalis L., this research was performed. The targeted chemical characterization of the extracts was achieved using the Ultra-High-Performance-Liquid-Chromatography-Linear-Trap-Mass-Spectrometry OrbiTrap instrumental technique, while Fourier Transform Infrared Spectroscopy was conducted to investigate the structural properties of the examined leaf extracts. According to the results, the species P. officinalis, Božurna locality as the origin of the plant material, and microwave-assisted extraction produced the maximum polyphenol yield, (491.9 ± 2.7 mg gallic acid equivalent (GAE)/mL).The ethanolic extracts exhibited moderate antioxidant activity as evaluated by DPPH (2,2-diphenyl-1-picrylhydrazyl) and phosphomolybdenum tests. With MIC values of 0.125 mg/mL, the leaf extracts produced by ultrasound-assisted extraction and maceration (Deliblato sands and Bogovo gumno) had the best antibacterial activity against Pseudomonas aeruginosa and Salmonella Typhimurium. Ultrasound-assisted extraction has proven to produce the most effective antimicrobial agents. Inhibitory potential towards glucosidase, amylase, cholinesterases, and tyrosinase was evaluated in enzyme inhibition assays and molecular docking simulations. Results show that leaves of P. tenuifolia L. obtained by ultrasound-assisted extraction had the highest acetylcholinesterase and butyrylcholinesterase inhibitory activity. Namely, the complexity of the polyphenol structures, the extraction method, the used locality, and the different mechanisms of the reactions between bioactives from leaf extracts and other components (free radicals, microorganisms, and enzymes) are the main factors that influence the results of the antioxidant tests, as well as the antibacterial and enzyme-inhibitory activities of the extracts. Hydroxymethyl-phenyl pentosyl-hexoside and acetyl-hydroxyphenyl-hexoside were the first time identified in the leaf extract of the Paeonia species. Due to their proven biological activities and the confirmed existence of bioactive compounds, leaf extracts may find use in foodstuffs, functional foods, and pharmaceutical products.

Nutritional composition, bioactive compounds, and pharmacological activities of tossa jute sprout (Corchorus olitorius L.): A potential functional food

This study investigated the food properties, phytochemical profiles, and pharmacological activities of tossa jute sprout, underscoring the exploration of its potential as a functional food. Tossa jute sprout is rich in protein, carbohydrate, fiber, total soluble solids, color content, total energy, vitamins, and minerals, with a lower fat and sugar content. Bioactive compound profiling found that it contains a significant quantity of total phenolics and flavonoids. The HPLC-DAD polyphenol profile detected ten compounds, with 3,4 dihydroxybenzoic acid being the most abundant compound, followed by (-) epicatechin, rosmarinic acid, kaempferol, catechin hydrate, caffeic acid, myricetin, catechol, trans-ferulic acid, and rutin hydrate. It has strong radical scavenging, reducing power, metal chelating power, and total antioxidant power, suggesting this sprout's ability to repair cellular oxidative damage or restore impaired cellular oxidative homeostasis. It also possesses strong α-glucosidase and pancreatic lipase inhibition activities, but mild α-amylase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibition activities support the sprout’s ability to lower blood sugar, suppress postprandial hyperglycemia, downregulate fat metabolism, and maintain or restore acetylcholine. Overall findings established tossa jute sprout’s high potential as a functional food in eliminating malnutrition, maintaining quality health, and eradicating or moderating ailments, including diabetes, obesity, and Alzheimer’s.

α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies

Chemical investigation of Carthamus tinctorius L. flowers resulted in isolation of seven metabolites that were identified as; p-Hydroxybenzoic acid (1), trans hydroxy cinnamic acid (2), kaempferol-6-C-glucoside (3), astragalin (4), cartormin (5), kaempferol-3-O-rutinoside (6), and kaempferol–3-O-sophoroside (7). Virtual screening of the isolated compounds against human intestinal α-glucosidase, acetylcholinesterase, and butyrylcholinesterase was carried out. Additionally, the antioxidant activity of the bioactive compounds was assessed. Compounds 1 and 5 exhibited moderate binding affinities to acetylcholinesterase (binding energy −5.33 and −4.18 kcal/mol, respectively), compared to donepezil. Compounds 1 to 7 demonstrated weak affinity to butyrylcholinesterase. Compound 4 displayed very strong binding affinity to human intestinal α-glucosidase, better than Acarbose (reference compound), meanwhile compound 2 exhibited lower affinity. Molecular dynamic studies revealed that compound 4 formed a stable complex with the binding site throughout a 100 ns simulation period. The in-vitro results were consistent with the virtual experimental results, as compounds 1 and 5 showed mild inhibitory effects on acetylcholinesterase (IC50s 150.6–168.7 µM). Compound 4 exhibited significant α-glucosidase inhibition with an IC50 of 93.71 µM. The bioactive compounds also demonstrated notable antioxidant activity in ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], ORAC (oxygen radical-absorbance capacity), and metal chelation assays, suggesting their potential in improving dementia in Alzheimer’s disease (AD) and mitigating hyperglycemia.

Characterization of Phenolic Compounds in Extra Virgin Olive Oil from Granada (Spain) and Evaluation of Its Neuroprotective Action.

The olive oil sector is a fundamental food in the Mediterranean diet. It has been demonstrated that the consumption of extra virgin olive oil (EVOO) with a high content of phenolic compounds is beneficial in the prevention and/or treatment of many diseases. The main objective of this work was to study the relationship between the content of phenolic compounds and the in vitro neuroprotective and anti-inflammatory activity of EVOOs from two PDOs in the province of Granada. To this purpose, the amounts of phenolic compounds were determined by liquid chromatography coupled to mass spectrometry (HPLC-MS) and the inhibitory activity of acetylcholinesterase (AChE) and cyclooxygenase-2 (COX-2) enzymes by spectrophotometric and fluorimetric assays. The main families identified were phenolic alcohols, secoiridoids, lignans, flavonoids, and phenolic acids. The EVOO samples with the highest total concentration of compounds and the highest inhibitory activity belonged to the Picual and Manzanillo varieties. Statistical analysis showed a positive correlation between identified compounds and AChE and COX-2 inhibitory activity, except for lignans. These results confirm EVOO's compounds possess neuroprotective potential.

Synthesis and Evaluation of Aminothiazole Hybrids as Potential Acetylcholinesterase Inhibitors

This study aimed to synthesize aminothiazole derivatives with 1,3,4-oxadiazole moiety and evaluated their acetylcholinesterase (AChE) and antioxidant activity in order to check their potency against Alzheimer's disease. Inhibition screening against AChE indicated that synthesized derivatives expressed well to moderate AChE inhibitory activity in vitro. Of the examined synthetic compounds (3a-i), compound 3d expressed the best inhibition with IC50-0.35 µM. The antioxidant activity of all the synthesized compounds was also analyzed by the DPPH assay. Finally, in molecular docking analysis, the best docking score was displayed by the most active compound 3d supported the in vitro inhibition results. Compound 3d emerged to be promising lead for the further development of anti- Alzheimer’s drugs.

Terpenoids from Alpinia galanga and their acetylcholinesterase inhibitory activity.

A new labdane diterpene (1), two new norsesquiterpenoids (2-3), as well as eight known terpenoids (4-11) were isolated from the seeds of Alpinia galanga (Zingiberaceae). Their structures and absolute configurations were elucidated by 1D, 2D NMR, MS, and comparison of their experimental and calculated electronic circular dichroism (ECD). The acetylcholinesterase (AChE) inhibitory activities of all the isolated compounds (1-11) were evaluated and the result showed that compounds 6 and 9 had inhibitory activity against AChE, with IC50 values at 295.70 and 183.91 μM, whereas other compounds did not show any inhibitory activity.

Integrated evaluation of the biological response of the earthworm Eisenia fetida using two glyphosate exposure strategies: soil enriched and soils collected from crops in Southeastern Mexico.

Under laboratory conditions, the toxicological effects of pesticides tend to be less variable and realistic than under field conditions, limiting their usefulness in environmental risk assessment. In the current study, the earthworm Eisenia fetida was selected as a bioindicator for assessing glyphosate toxic effects in two different trials to solve this dilemma. In Trial 1, the worms were exposed for 7 and 14days to concentrations of a commercial glyphosate formulation (1 to 500mg a.i. kg-1) currently used in the field. In Trial 2, the worms were kept in nine soils collected from different plots with crops for 14days of exposure. In both experiments, glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and acetylcholinesterase (AChE) activities and contents of lipid peroxidation (LPO) were evaluated. In T1, the glyphosate formulation produced a 40% inhibition of AChE activity and a significant increase in GST, SOD, CAT, and GPx activities and LPO contents in E. fetida on day 7. In T2, higher concentrations of glyphosate were detected in the soils of soybean, papaya, and corn (0.92, 0.87, and 0.85mgkg-1), which induced a positive correlation between the levels of glyphosate residues with GST, SOD, CAT, GPx, and LPO and a negative correlation with AChE. These findings indicate that crop soils polluted with glyphosate elicited higher oxidative stress than under laboratory conditions, confirmed by IBRv2, PCA, and AHC analyses.

Marrubium vulgare Extract Improves Spatial Working Memory and Oxidative Stress Damage in Scopolamine-Treated Rats.

The cholinergic neuronal loss in the basal forebrain and increasing brain oxidative stress are one of the main features of the brain suffering from Alzheimer's disease. Marrubium vulgare (M. vulgare), commonly known as 'white horehound,' possesses a variety of valuable properties, such as antioxidative, anti-inflammatory, and antidiabetic activities. Moreover, it possesses neuromodulatory properties that could potentially impact short-term memory functions. The present study was undertaken to investigate the preventive effects of water M. vulgare extract on working memory, cholinergic neurotransmission, and oxidative stress in rats with scopolamine (Sco)-induced dementia. Male Wistar rats (200-250 g) were divided into four experimental groups. The plant extract was administered orally for 21 days, and Sco (2 mg/kg) was administered intraperitoneally for 11 consecutive days. The behavioral performance of the animals was evaluated by the T-maze test. The effect of the extract on acetylcholinesterase (AChE) activity and antioxidant status in cortex and hippocampus were also monitored. Our experimental data revealed that treatment with M. vulgare significantly increased the percentage of correct choices of rats with Sco-induced dementia in the T maze test (by 38%, p < 0.05). Additionally, it reduced AChE activity in the hippocampus (by 20%, p < 0.05) and alleviated oxidative stress induced by Sco, particularly in the cortex. M. vulgare water extract demonstrated working memory preserving effect in rats with Sco-induced dementia, AChE inhibitory activity and in vivo antioxidant potential, and deserve further attention.

Ecotoxicological strategies employing biochemical markers and organisms to monitor the efficacy of malathion photolysis treatment

The objective of this study was to assess the photolysis-mediated degradation of malathion in standard and commercial formulations, and to determine the toxicity of these degraded formulations. Degradation tests were carried out with 500 μg L−1 of malathion and repeated three times. The initial and residual toxicity was assessed by using Lactuca sativa seeds for phytotoxicity, Stegomyia aegypti larvae for acute toxicity, and Stegomyia aegypti mosquitoes (cultivated from the larval stage until emergence as mosquitoes) to evaluate the biochemical markers of sublethal concentrations. For the standard formulations the photolytic process efficiently reduced the initial concentration of malathion to levels below the regulatory limits however, the formation of byproducts was revealed by chromatography, which allowed for a more complete proposal of photolytic-mediated malathion degradation route. The degraded formulations inhibited the growth of L. sativa seeds, while only the untreated formulations showed larvicidal activity and mortality. Both formulations slightly inhibited acetylcholinesterase activity in S. aegypti mosquitoes, while the standard formulation decreased and the commercial formulation increased glutathione S-transferase activity. However, there were no significant differences for superoxide dismutase, esterase-α, esterase-β and lipid peroxidation. These findings indicate that in the absence of the target compound, the presence of byproducts can alter the enzymatic activity. In general, photolysis effectively degrade malathion lower than the legislation values; however, longer treatment times must be evaluated for the commercial formulation.

Discovery of (±)-Penindolenes Reveals an Unusual Indole Ring Cleavage Pathway Catalyzed by P450 Monooxygenase.

(±)-Penindolenes A-D (1-4), the first representatives of indole terpenoids featuring a γ-lactam skeleton, were isolated from the mangrove-derived endophytic fungus Penicillium brocae MA-231. Our bioactivity tests revealed their potent antimicrobial and acetylcholinesterase inhibitory activities. The biosynthetic reactions by the five enzymes PbaABCDE leading to γ-lactam ring formation were identified with heterologous expression and in vitro enzymatic assays. Remarkably, the cytochrome P450 monooxygenase PbaB and its homolog in Aspergillus oryzae catalyzed the 2,3-cleavage of the indole ring to generate two keto groups in 1, in different manners from well-known tryptophan dioxygenases. This is the first example of the oxidative cleavage of indole by a P450 monooxygenase. In addition, rare secondary amide bond formation by the glutamine synthetase-like enzyme PbaD was reported. These findings will contribute to the engineered biosynthesis of unnatural, bioactive indole terpenoids.

Classification of buckwheat honey produced in Kazakhstan according to their biochemical ingredients and bioactivities by chemometric approach

Herein, nineteen buckwheat honey samples collected from 19 stations of different ecological zones of Kazakhstan were analysed for their pollen density, physicochemical properties, chemical composition, antioxidant, anticholinesterase, tyrosinase inhibitory, and urease inhibitory activities with chemometric approaches. Twelve phenolic compounds and fumaric acid were identified using HPLC-DAD, and mainly fumaric, p-hydroxybenzoic, p-coumaric, trans-2-hydroxy cinnamic acids, and chrysin were detected in all samples. The honey samples collected from the Northern zone exhibited best antioxidant activity in lipid peroxidation inhibitory (IC50:8.65 ± 0.50 mg/mL), DPPH• (IC50:17.07 ± 1.49 mg/mL), ABTS•+ (IC50:8.90 ± 0.65 mg/mL), CUPRAC (A0.50:7.51 ± 0.30 mg/mL) and metal chelating assay (IC50:10.39 ± 0.71 mg/mL). In contrast, South-eastern zone samples indicated better acetylcholinesterase (55.57 ± 0.83%), butyrylcholinesterase (49.59 ± 1.09%), tyrosinase (44.40 ± 1.21%), and moderate urease (24.57 ± 0.33%) inhibitory activities at 20 mg/mL. The chemometric classification of nineteen buckwheat honey was performed using PCA and HCA techniques. Both were supported by correlation analysis. Thirteen compounds contributed significantly to the clustering of buckwheat honey based on geographical origin.

PED: a novel predictor-encoder-decoder model for Alzheimer drug molecular generation.

Alzheimer's disease (AD) is a gradually advancing neurodegenerative disorder characterized by a concealed onset. Acetylcholinesterase (AChE) is an efficient hydrolase that catalyzes the hydrolysis of acetylcholine (ACh), which regulates the concentration of ACh at synapses and then terminates ACh-mediated neurotransmission. There are inhibitors to inhibit the activity of AChE currently, but its side effects are inevitable. In various application fields where Al have gained prominence, neural network-based models for molecular design have recently emerged and demonstrate encouraging outcomes. However, in the conditional molecular generation task, most of the current generation models need additional optimization algorithms to generate molecules with intended properties which make molecular generation inefficient. Consequently, we introduce a cognitive-conditional molecular design model, termed PED, which leverages the variational auto-encoder. Its primary function is to adeptly produce a molecular library tailored for specific properties. From this library, we can then identify molecules that inhibit AChE activity without adverse effects. These molecules serve as lead compounds, hastening AD treatment and concurrently enhancing the AI's cognitive abilities. In this study, we aim to fine-tune a VAE model pre-trained on the ZINC database using active compounds of AChE collected from Binding DB. Different from other molecular generation models, the PED can simultaneously perform both property prediction and molecule generation, consequently, it can generate molecules with intended properties without additional optimization process. Experiments of evaluation show that proposed model performs better than other methods benchmarked on the same data sets. The results indicated that the model learns a good representation of potential chemical space, it can well generate molecules with intended properties. Extensive experiments on benchmark datasets confirmed PED's efficiency and efficacy. Furthermore, we also verified the binding ability of molecules to AChE through molecular docking. The results showed that our molecular generation system for AD shows excellent cognitive capacities, the molecules within the molecular library could bind well to AChE and inhibit its activity, thus preventing the hydrolysis of ACh.

Lathyrane and premyrsinane Euphorbia diterpenes against Alzheimer's disease: Bioinspired synthesis, anti-cholinesterase and neuroprotection bioactivity

The first systematic acylated diversification of naturally scarce premyrsinane diterpenes, together with their biosynthetic precursors lathyrane diterpene were carried out. Two new series of premyrsinane derivates (1a-32a) and lathyrane derivates (1–32) were synthesized from the naturally abundant lathyrane diterpene Euphorbia factor L3 through a bioinspired approach. The cholinesterase inhibitory and neuroprotective activities of these diterpenes were investigated to explore potential anti-Alzheimer's disease (AD) bioactive lead compounds. In general, the lathyrane diterpenes showed the better acetylcholinesterase (AChE) inhibitory activity than that of premyrsinanes. The lathyrane derivative 17 bearing a 3-dimethylaminobenzoyl moiety showed the best AChE inhibition effect with the IC50 value of 7.1 μM. Molecular docking demonstrated that 17 could bond with AChE well (−8 kal/mol). On the other hand, premyrsinanes showed a better neuroprotection profile against H2O2-induced injury in SH-SY5Y cells. Among them, the premyrsinane diterpene 16a had significant neuroprotective effect with the cell viability rate of 113.5 % at 12.5 μM (the model group with 51.2 %). The immunofluorescence, western blot and reactive oxygen species (ROS) analysis were conducted to demonstrate the mechanism of 16a. Furthermore, a preliminary SAR analysis of the two categories of diterpenes was performed to provide the insights for anti-AD drug development.

The impact of seasonal variation on the composition of the volatile oil of Polyalthia suberosa (Roxb.) Thwaites leaves and evaluation of its acetylcholinesterase inhibitory activity

BackgroundPolyalthia suberosa (Roxb.) Thwaites (Annonaceae) is a medicinal plant that has been reported for its various pharmacological potentials, such as its anti-inflammatory, analgesic, antioxidant, and neuropharmacological activities. This study aimed to analyze the leaf essential oils of P. suberosa (PSLO) collected in different seasons, to evaluate the acetylcholinesterase inhibitory activity, and to corroborate the obtained results via in-silico molecular docking studies.MethodsThe leaf essential oils of P. suberosa collected in different seasons were analyzed separately by GC/MS. The acetylcholinesterase inhibitory activity of the leaves oil was assessed via colorimetric assay. In-silico molecular docking studies were elucidated by virtual docking of the main compounds identified in P. suberosa leaf essential oil to the active sites in human acetylcholinesterase crystal structure.ResultsA total of 125 compounds were identified where D-limonene (0.07 − 24.7%), α-copaene (2.25 − 15.49%), E-β-caryophyllene (5.17 − 14.42%), 24-noroleana-3,12-diene (12.92%), β-pinene (0.14 − 8.59%), and α-humulene (2.49–6.9%) were the most abundant components. Results showed a noteworthy influence of the collection season on the chemical composition and yield of the volatile oils. The tested oil adequately inhibited acetylcholinesterase enzyme with an IC50 value of 91.94 µg/mL. Additionally, in-silico molecular docking unveiled that palmitic acid, phytol, p-cymene, and caryophyllene oxide demonstrated the highest fitting scores within the active sites of human acetylcholinesterase enzyme.ConclusionsFrom these findings, it is concluded that P. suberosa leaf oil should be evaluated as a food supplement for enhancing memory.

Dehydration, Rehydration and Thermal Treatment: Effect on Bioactive Compounds of Red Seaweeds Porphyra umbilicalis and Porphyra linearis.

The nutritional and bioactive value of seaweeds is widely recognized, making them a valuable food source. To use seaweeds as food, drying and thermal treatments are required, but these treatments may have a negative impact on valuable bioactive compounds. In this study, the effects of dehydration, rehydration, and thermal treatment on the bioactive compounds (carotenoids, phycobiliproteins, total phenolic content (TPC), total flavonoids content (TFC)), antioxidant (ABTS and DPPH radical scavenging activities) and anti-Alzheimer's (Acetylcholinesterase (AchE) inhibitory activities, and color properties of Porphyra umbilicalis and Porphyra linearis seaweeds were evaluated. The results revealed significant reductions in carotenoids, TPC, TFC, and antioxidant activities after the seaweeds' processing, with differences observed between species. Thermal treatment led to the most pronounced reductions in bioactive compound contents and antioxidant activity. AchE inhibitory activity remained relatively high in all samples, with P. umbilicalis showing higher activity than P. linearis. Changes in color (ΔE) were significant after seaweeds' dehydration, rehydration and thermal treatment, especially in P. umbilicalis. Overall, optimizing processing methods is crucial for preserving the bioactive compounds and biological activities of seaweeds, thus maximizing their potential as sustainable and nutritious food sources or as nutraceutical ingredients.