Search Results (666)

This study evaluated the extraction efficiency of two Natural Deep Eutectic Solvents (NADESs), glycerol–urea (1:1) and citric acid–sorbitol (1:2), for recovering phenolic compounds from the different parts of the fruit (pulp, seed-containing pulp, seeds, and peel) of Opuntia robusta and Opuntia ficus-indica in comparison with 50% methanol. Phytochemical profiling was performed using ultra-high-performance liquid chromatography–high-resolution mass spectrometry, alongside antioxidant and enzyme inhibition assessments (acetylcholinesterase, butyrylcholinesterase, tyrosinase, α-glucosidase, and α-amylase). Glycerol–urea performed similarly to methanol in extracting phenolic compounds with notable antioxidant properties. Peel extracts contained the highest levels of bioactive compounds, particularly phenolic acids (525.49 in O. robusta and 362.96 µg/g_DW in O. ficus indica). Enzyme inhibition varied across species and fruit parts, with extracts from both species inhibiting all targeted enzymes. Notably, this study provides the first evidence of tyrosinase inhibitory activity in O. robusta, which exhibited the strongest inhibition. Overall, these results emphasize the potential of cactus fruit extracts, particularly from O. robusta, for valorization, and support the use of NADESs as a sustainable and medium for extracting antioxidant compounds. Furthermore, the potential of fruit peel as waste with nutraceutical applications was demonstrated. Full article

The current study investigates the modulatory effects of gallic acid (GA), 3-hydroxytyrosol (3-HT), and quercetin (QUE) on key cholinesterase enzymes using Drosophila melanogaster (fruit fly) head homogenates as a source of central cholinesterases following in vivo larval exposure. The choice of these plant phenolics was predicated on their cholinesterase (ChE) inhibitory effect reported recently by our group. The study utilized D. melanogaster larvae subjected to varying doses of GA, 3-HT, and QUE, subsequently evaluating enzymatic activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Galanthamine HBr was used as a positive control. All three phenolic compounds exhibited elevated ΔOD/min values for BChE inhibition compared to the negative control (ethanol). GA and QUE inhibited AChE, though with lower potency than galanthamine; at 1 mM, GA and QUE achieved 79.23% and 80.98% inhibition, respectively, compared to 98.34% for galanthamine. Interestingly, the effect of 3-HT on AChE was inversely related to the dose. The results indicate that GA and QUE modulate cholinesterase activity in vivo, consistent with our prior in vitro reports. This study also provides the first in vivo evidence of 3-HT’s ChE-modulating activity in Drosophila within a whole-organism model. Full article

Cholinergic dysfunction is a hallmark of Alzheimer’s disease (AD), driven by elevated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity that depletes acetylcholine and contributes to amyloid pathology. Current AD treatments face major challenges, including poor brain penetration, short effect duration and safety concerns, highlighting the need for compounds suitable for preventive or earlier-stage intervention. This study investigated marine phytohormones as modulators of cholinergic imbalance, using an integrative strategy encompassing enzymatic assays, QSAR and DFT calculations, molecular docking, molecular dynamics (MD) simulations, and ADMET profiling. Among them, isopentenyl adenine (IPA) and abscisic acid (ABA) showed inhibitory activity against cholinesterases. IPA inhibited both AChE and BChE through distinct mechanisms with noncompetitive inhibition of AChE and competitive inhibition of BChE, while ABA showed selective noncompetitive inhibition of AChE. DFT-based analysis revealed distinct electronic properties supporting differential reactivity. Moreover, IPA interacted with both catalytic and peripheral residues in AChE, and aligned with BChE’s active site, while ABA was bound more peripherally. MD simulations confirmed complex-specific conformational stability based on RMSD, RMSF, Rg, and hydrogen bonding analysis. Both compounds showed low off-target potential against serine proteases and favorable predicted ADMET profiles. These results support the potential of marine phytohormones as preventive modulators of cholinergic dysfunction in AD. Full article

Acetylcholinesterase (AChE) is an important molecular target in the development of insecticides, but due to also being found in the human body, it is necessary to characterize the inhibitory profile of compounds to achieve selectivity. In this study, we employed molecular modeling and 3D-QSAR approaches to identify novel compounds that inhibit AChE1 in Bemisia tabaci, a common agricultural pest in tropical and subtropical crops. We conducted molecular docking simulations and quantitative structure–activity relationship analysis (QSAR) to identify compounds with potential inhibitory activity and to develop a predictive model for the activity of these new compounds. The validated model demonstrated remarkable predictive performance. Using the model, we screened a library of novel moieties in favorable regions of the most active molecules in the dataset and identified promising candidates, including FS168. We performed molecular dynamics simulations with FS168 bound to the AChE1 of B. tabaci and observed stabilization and interaction with important catalytic amino acids, indicating a potential inhibition mechanism. Our results showcase the potential of combining molecular modeling and 3D-QSAR approaches for discovering new potential AChE1 inhibitors in Bemisia tabaci as selective agrochemicals. Full article

This study reports the first chemical characterization of the essential oil of Croton alnifolius. A very low yield of 0.028% ± 0.0012 (w/w) was obtained by steam distillation for 4 h using a Clevenger-type apparatus. The chemical composition of the oil was analyzed by gas chromatography coupled with mass spectrometry (GC–MS) for compound identification and by gas chromatography with a flame ionization detector (GC–FID) for quantification. A total of 49 compounds were identified, representing 94.65% of the total oil composition. The chemical profile was dominated by hydrocarbon sesquiterpenes (53.11%) and hydrocarbon monoterpenes (32.20%). The major constituents included (E)-caryophyllene (17.42%), α-pinene (14.53%), myrcene (9.51%), germacrene D (9.92%), and β-chamigrene (5.48%). The biological activity of the essential oil was also evaluated: it exhibited weak antimicrobial activity against Enterococcus faecium with a Minimum Inhibitory Concentration (MIC) value of 1000 μg/mL, strong antioxidant potential in the ABTS assay (SC₅₀ = 28.43 ± 1.0 μg/mL), and moderate acetylcholinesterase inhibitory activity (61.74 ± 1.02 μg/mL). These results indicate that the unique sesquiterpene rich chemical profile of C. alnifolius contributes to its antioxidant and neuroprotective potential, supporting its relevance as a promising source of bioactive natural products. Full article

This study aimed to isolate and screen lactic acid bacteria (LAB) with neuroprotective potential for food applications. Fifteen strains were screened for probiotic potential properties, γ-aminobutyric acid (GABA) production, and acetylcholinesterase (AChE) inhibitory activity. Lactobacillus delbrueckii AY8 and AY15 demonstrated the strongest probiotic potential, AChE inhibitory activity, and GABA production. Whole-genome sequencing confirmed genes linked to these probiotic and neuroprotective traits. To assess their functionality in a food matrix, the strains were used as adjunct cultures in fermented milk with and without jujube kernel powder (JP). Fermentation with the AY8 strain in JP-fortified milk significantly increased bioactive compounds, resulting in higher total phenolic content (235.75 mg GAE/g), flavonoids (114.07 mg RE/g), and superior antioxidant activity (110.24 mg Ascorbic equivalent/100 g). This biotransformation led to a remarkable increase in AChE inhibition, with the AY8-fermented sample achieving 30.66% inhibition, significantly higher than the JP control (18.27%) and the plain control (12.30%). The combination also improved the product’s viscosity and sensory profile. This study highlights the successful discovery of novel L. delbrueckii strains, whose application in a food model, when combined with a plant-based supplement, creates a functional food with enhanced neuroprotective potential, underscoring the role of microbial metabolism in food functionality. Full article

Tordylium trachycarpum Boiss. (Apiaceae) has long been used by traditional healers in the Kurdistan Region of Iraq to alleviate gastrointestinal disorders and oral inflammation; however, its phytochemical composition and pharmacological properties remain scientifically unverified. In this study, we report the first phytochemical profiling and plant-assisted synthesis of copper nanoparticles (CuNPs) using the methanolic extract of T. trachycarpum as a natural reducing and stabilizing agent. The synthesized nanoparticles were characterized using UV–Vis spectroscopy, FTIR spectroscopy, X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), and Energy-Dispersive X-ray Spectroscopy (EDS) analyses, confirming their nanoscale formation, crystallinity, and elemental composition. Gas chromatography–mass spectrometry (GC–MS) identified 22 bioactive metabolites, with methoxsalen (30.91%), triphenylphosphine oxide (12.54%), desulphosinigrin (10.79%), isopimpinellin (6.72%), and α-glyceryl linolenate (6.39%) as the predominant constituents. Both the crude extract and the biosynthesized CuNPs were evaluated for their antimicrobial, antioxidant, and enzyme inhibitory activities. The CuNPs displayed enhanced antimicrobial potency, with MIC values of 250 µg/mL against Klebsiella pneumoniae and Candida albicans, and 500 µg/mL against Pseudomonas aeruginosa and Staphylococcus epidermidis. They also exhibited superior antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), cupric ion reducing antioxidant capacity (CUPRAC), and metal chelating activity (MCA) assays, along with moderate inhibition of key metabolic and neurological enzymes, including acetylcholinesterase and tyrosinase. These findings highlight T. trachycarpum as a promising phytochemical source for sustainable nanoparticle synthesis and reveal the multifunctional potential of biosynthesized CuNPs as antioxidant and antimicrobial agents with prospective applications in drug discovery and nanomedicine. Full article

Background: Cardanol, a bioactive alkylphenol obtained from technical cashew nutshell liquid (CNSL), consists of mono-, di-, and tri unsaturated side chain derivatives. These compounds are of increasing interest for their diverse industrial applications. Methods: In this study, three major cardanol components—3-[(8E)-8-pentadecen-1-yl] phenol (C1), 3-[(8E,11E)-8,11-pentadecadien-1-yl] phenol (C2), and 3-[(8E,11E,14E)-8,11,14-pentadecatrien-1-yl] phenol (C3)—were isolated from CNSL via chromatographic separation. Their structures were confirmed by FTIR and detailed ¹H and ¹³C NMR spectroscopy, with complete carbon and proton assignments reported. Results: Among the three, C3 exhibited the highest antioxidant potential, with a DPPH IC₅₀ value of 0.179 ± 0.005 mg/mL, approximately five times more potent than C1 (IC₅₀ = 1.000 ± 0.200 mg/mL). C3 also showed the highest lethality against Artemia salina (LC₅₀ = 4.118 ± 0.328 mg/mL) and the most pronounced inhibition of acetylcholinesterase (AChE), with a 0.8 cm inhibition zone. Computational studies using molecular docking and molecular dynamics simulations further supported the interaction of these compounds with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Conclusions: These results expand our understanding of the chemical composition and potential applications of CNSL. The identified unsaturated alkylphenols, particularly the triene compound, demonstrate promise as sustainable candidates for the development of new materials and pharmaceuticals that combat oxidative stress and neurodegenerative diseases. Full article

Antarctic algae have evolved in extreme environmental conditions, developing unique metabolic adaptations with significant biotechnological potential. In this study, we explored the bioactivity of the sea-ice microalga Microglena antarctica by preparing acetone and methanol extracts from biomass cultivated at 4, 8, and 16 °C. These extracts were screened for their in vitro antioxidant properties and inhibitory activities on enzymes related to Alzheimer’s disease (acetylcholinesterase: AChE, butyrylcholinesterase: BChE), type 2 diabetes mellitus (T2DM, α-glucosidase, α-amylase), obesity (lipase), and hyperpigmentation (tyrosinase). Our screening revealed a high capacity of acetone extracts to scavenge the ABTS•⁺ radical (EC₅₀ ranging from 3.57 to 4.18 mg mL⁻¹), along with strong copper chelating activity in both acetone and methanol extracts (EC₅₀ values of 6.31 and 6.41 mg mL⁻¹). Relevant inhibition towards α-amylase (IC₅₀ values of 3.34 and 4.53 mg mL⁻¹) and tyrosinase (with IC₅₀ ranging from 3.82 to 5.47 mg mL⁻¹) was reported for acetone and methanol extracts, respectively. UHPLC-HRMS-based profiling revealed the presence of lipidic molecules, such as glycolipids, phospholipids, and betaine lipids with polyunsaturated carbon chains, together with carotenoids, including canthaxanthin and adonixanthin, which are likely responsible for the observed bioactivities. Full article

Acetylcholinesterase (AChE) is a key enzyme responsible for terminating cholinergic neurotransmission by hydrolyzing acetylcholine. While clinically approved AChE inhibitors such as donepezil, rivastigmine, and galantamine are used in the symptomatic treatment of Alzheimer’s disease and related dementias, little is known about the modulatory effects of common dietary compounds on AChE activity. In this study, we investigated the influence of creatine (CR) and taurine (TA)—two widely consumed nutritional supplements with reported neuroprotective and cognitive-enhancing properties—on AChE. Enzyme kinetics were evaluated using a modified Ellman’s method, and Lineweaver–Burk analyses revealed that both CR and TA act as competitive inhibitors. Calculated parameters (Km, Vmax), inhibition constants (Ki), and half maximal inhibitory concentrations (IC₅₀) consistently indicated stronger potency for CR (IC₅₀ = 0.0056 ± 0.00018 mM) compared to TA (IC50 = 0.0097 ± 0.00035 mM). To complement the experimental data, molecular docking was performed using two crystal structures of human AChE. Docking confirmed that both ligands preferentially occupy the active-site region in a manner consistent with competitive inhibition, with CR showing more favorable binding scores than TA. Although markedly weaker than clinical drugs, these findings provide the first biochemical and in silico evidence that CR and TA directly interact with AChE, suggesting subtle cholinergic modulation relevant to cognitive function and neuroprotection. Full article

The Amaryllidaceae family represents a prolific source of pharmacologically active compounds, boasting over 700 diverse alkaloids identified to date. However, the genus Eustephia (Amaryllidoideae subfamily) remains largely unexplored. This study focused on the alkaloid profiles and pharmacological potential of bulb and leaves extracts from three Peruvian Eustephia species (E. coccinea, E. darwinii, and E. hugoei). The phenolic and flavonoid levels as well as the antioxidant activity of the methanolic extracts, were determined. Twenty-six alkaloids were identified in the alkaloid-enriched extracts (AEEs). Homolycorine-type alkaloids predominated in E. darwinii and E. hugoei, whereas E. coccinea displayed greater chemical diversity showing assoanine as the main detected alkaloid. In addition, candimine was widely distributed across species. AEEs showed stronger enzyme inhibition of acetylcholinesterase (AChE) compared to butyrylcholinesterase (BuChE). Notably, the AEE from E. coccinea leaves showed the highest AChE inhibition (IC₅₀ = 1.82 μg/mL), while the AEE from bulbs exhibited the strongest BuChE inhibitory activity (IC₅₀ = 61.22 μg/mL). Regarding anti-T. cruzi effect, the E. darwinii bulbs AEE was most potent and selective against amastigote forms (IC₅₀ = 2.1 μg/mL; SI = 8.83). These findings underscore the potential of Peruvian Eustephia species as promising sources of pharmacologically relevant alkaloids, with possible applications in neurodegenerative disorders and Chagas disease. Full article

Gmelina philippensis Cham. (Lamiaceae) is a traditionally valued medicinal plant with unexplored potential for the management of neurodegenerative disorders. In the present study, the phytochemical profile of its methanolic leaf extract was comprehensively characterized using untargeted liquid chromatography–tandem mass spectrometry metabolomics (LC–MS/MS) and molecular networking. In addition, the extract was evaluated for its antioxidant and cholinesterase inhibitory activities relevant to Alzheimer’s disease (AD). Metabolite profiling led to the annotation of 27 compounds, with a predominance of flavonoids and iridoid glycosides unique to the genus Gmelina, along with phenolic acids, lipids, and other minor compounds. The extract exhibited potent in vitro antioxidant activity, with an IC₅₀ of 7.49 ± 0.002 μg/mL in the DPPH assay and 639.63 ± 0.814 μg AAE/mg in the FRAP assay. Notably, the extract showed significant inhibitory activity against acetylcholinesterase and butyrylcholinesterase, with an IC₅₀ of 4.87 ± 0.16 and 40.99 ± 0.03 μg/mL, respectively. Molecular networking further supported the metabolite annotation and highlighted clusters of bioactive iridoids and flavonoids. Overall, these findings highlight that G. philippensis as a rich source of multi-target bioactive compounds, supporting that the extract has good anti-acetylcholinesterase activity comparable to the rivastigmine that used in neurodegenerative disease. This study provides a promising foundation for the development of novel therapeutic approaches targeting neurodegenerative diseases. Full article

Alzheimer’s disease continues to be one of the most urgent neurodegenerative conditions, with acetylcholinesterase (AChE) inhibitors serving as a fundamental component of contemporary treatment approaches. Growing evidence underscores that marine ecosystems are a rich source of structurally varied and biologically active natural products exhibiting anticholinesterase properties. This review presents a thorough synthesis of marine-derived metabolites—including those sourced from bacteria, fungi, sponges, algae, and other marine life—that demonstrate inhibitory effects against AChE and butyrylcholinesterase (BuChE). Numerous compounds, such as meroterpenoids, alkaloids, peptides, and phlorotannins, not only show nanomolar to micromolar inhibitory activity but also reveal additional neuroprotective characteristics, including antioxidant effects, anti-amyloid properties, and modulation of neuronal survival pathways. Despite these encouraging findings, the transition to clinical applications is hindered by a lack of comprehensive pharmacokinetic, toxicity, and long-term efficacy studies. The structural variety of marine metabolites provides valuable frameworks for the development of next-generation cholinesterase inhibitors. Further interdisciplinary research is essential to enhance their therapeutic potential and facilitate their incorporation into strategies for addressing Alzheimer’s disease and related conditions. Full article

The valorization of olive oil production residues represents an innovative and sustainable strategy aligned with circular economy principles and the United Nations Sustainable Development Goals. In this study, we aimed to explore the phytochemical composition and neuroprotective potential of organic extracts obtained from olive pomace of the Arbequina and Arbosana cultivars. Extracts were prepared through solid–liquid extraction and analyzed by high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS), enabling the comprehensive identification of bioactive metabolites. The analysis revealed a diverse profile of phenolic compounds, including hydroxytyrosol, tyrosol, and multiple oleuropein derivatives, as well as triterpenic acids such as oleanolic and maslinic acids. These compounds are widely recognized for their antioxidant, anti-inflammatory, and neuroprotective activities. The antioxidant potential of the extracts was evaluated in vitro using DPPH and ABTS radical scavenging assays, showing significant activity comparable to that of standard antioxidants. Moreover, cholinesterase inhibitory assays demonstrated moderate to strong inhibition of acetylcholinesterase, an enzyme implicated in neurodegenerative diseases such as Alzheimer’s disease. To further elucidate the molecular basis of these effects, in silico molecular docking studies were performed on the most abundant compounds, revealing favorable binding affinities and interactions with key active site residues of acetylcholinesterase. Overall, these findings highlight olive pomace as a promising, underutilized source of bioactive compounds with potential applications in the development of functional foods, nutraceuticals, and neuroprotective therapeutic agents. The integration of in vitro and in silico approaches strengthens the evidence supporting the use of these extracts in future biomedical and industrial applications. Full article

Background: Virtual screening is a widely adopted technique for the discovery of novel pharmacologically active compounds; however, the risk of identifying false positive hits remains a major challenge. Aim: The aim of this study was to perform a validated structure-based drug design screening to discover multitarget pyrrole-based molecules as selective dual-acting monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitors. Methods: The study employed validated docking protocols using Glide (Schrödinger) and GOLD (CCDC), integrating ligand enrichment analysis and robust Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring. These methods were applied to a custom-designed database of pyrrole-based compounds. The top-ranked hits were synthesized and validated through in vitro tests, demonstrating significant inhibitory activities against MAO-A, MAO-B, AChE, and Butyrylcholinesterase (BChE). Results: The docking protocols achieved favorable hit rates, with 25.93% for AChE inhibitors and 44.44% for MAO-B inhibitors. Additionally, structure–activity relationship analysis revealed key substituent effects that significantly influence binding affinity and selectivity. Two compounds, EM-DC-19 (2-(2,5-dimethyl-1H-pyrrol-1-yl)-3-(2H-imidazol-4-yl)propanoic acid) and EM-DC-27 ([4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl]acetic acid), were identified as selective MAO-B inhibitors with additional moderate AChE inhibitory activity, demonstrating IC₅₀ values of 0.299 ± 0.10 µM and 0.344 ± 0.10 µM against MAO-B, and 76.15 ± 6.12 µM and 375.20 ± 52.99 µM against AChE, respectively. The absence of statistically significant inhibitory effects of these lead compounds on MAO-A and BChE (IC₅₀ > 100 µM) underscores their selective inhibitory activity towards MAO-B and AChE. Furthermore, both compounds demonstrated low neurotoxicity and significant neuroprotective and antioxidant effects in rat brain synaptosomes, mitochondria, and microsomes. These effects were particularly evident in models of 6-hydroxydopamine-induced neurotoxicity (6-OHDA) and oxidative stress induced by tert-butyl hydroperoxide and Fe²⁺/ascorbic acid. Conclusions: The findings suggest that these multitarget compounds hold promise for further development, with potential for structural modifications to enhance their enzyme inhibitory and neuroprotective properties. Full article