Search Results (1,201)

Background/Objectives: Alzheimer’s disease (AD) is a multifactorial neurodegenerative condition characterised by cognitive impairment, cholinergic deficiency and neuroinflammation. Carvacrol and thymol are two related natural monoterpenes with reported antioxidant, anti-inflammatory, anti-apoptotic and cholinesterase-inhibiting properties. This scoping review aims to map the current evidence regarding the effects of carvacrol and thymol on AD-related pathologies and identify their mechanisms of action. Methods: A systematic literature search was conducted in February 2026 across PubMed, Scopus and Web of Science. This review included original, English-language primary research articles investigating the effects of carvacrol and thymol on AD using in vitro, in vivo, or in silico models. Results: From an initial pool of 87 unique records, 30 primary studies met the inclusion criteria, encompassing direct AD pathology models (e.g., amyloid-beta), AD-associated risk models (e.g., metabolic or hypertensive impairment), and general cognitive impairment models. Both carvacrol and thymol reduced escape latency during spatial learning acquisition training and increased time spent in the target quadrant during probe trials, indicating improvements in both learning and memory retention, although several studies reported non-linear relationships. At the cellular level, carvacrol and thymol modulated distinct redox and inflammatory pathways, including nuclear factor erythroid 2-related factor 2 upregulation and tumour necrosis factor-alpha suppression. Synthetic derivatives and nanocarrier formulations (e.g., liposomes, nanoemulsions) demonstrated enhanced acetylcholinesterase inhibition and biological stability relative to parent monoterpenes. No clinical trials were identified, and formal critical appraisal was not performed. Conclusions: Preclinical evidence indicates that carvacrol and thymol show potential multi-targeted neuroprotective activity across diverse models of cognitive dysfunction. However, clinical translation remains unproven due to heterogeneous experimental designs, pharmacokinetic limitations, a lack of human trials, and unassessed study quality. Full article

Chlorpyrifos (CPF) is the most commonly used organophosphorus insecticide in agriculture globally. This has raised concerns due to its persistence, bioaccumulation, neurotoxicity, and environmental and human health effects. Until 2020, CPF was the most commonly used pesticide in European Union (EU) food production. CPF is also used in other parts of the world, though it has been discontinued in the EU, as national pesticide surveillance programs indicate it is found in soil, water, and food. This type of persistence is potentially harmful to farmers, consumers, and animals because CPF is toxic. Markedly, CPF has the potential to change the microbiota composition of soils, i.e., fungal, bacterial, and actinomycete communities, and inhibit the mineralization of nitrogen. The key CPF activity is associated with the inhibition of acetylcholinesterase (AChE), leading to reproductive, neurotoxic, and genotoxic effects. Microbial degradation, especially when applied by means of bacteria, has become one of the promising alternatives to the traditional physicochemical means since it is inexpensive, does not harm the environment and may possibly be fully detoxified. This review summarizes the latest developments in the study of CPF-degrading bacteria, enzyme pathways, microbial diversity, and the evaluation of the environmental impact of microbial remediation. Recent research findings, genomic research developments, and potential applications of CPF-degrading bacteria are addressed. In addition, this study reveals the current knowledge gaps, presents biotechnological challenges, and suggests future directions in the application of field-scale studies, focusing on the application of microbial solutions in sustainable agriculture. Full article

The search for new compounds capable of inhibiting the activity of enzymes involved in the development of neurodegenerative diseases, including Alzheimer’s disease, has attracted continuing interest for many years. Natural isothiocyanates and their synthetic analogs, as well as compounds containing a 1,3,5-triazine core, constitute a group of molecules with complex mechanisms of action involving multiple molecular targets. Although literature data confirm the activity of both isothiocyanates and s-triazines, these two active fragments have not yet been combined, and it remains unclear whether a synergistic effect can be achieved. In this study, 11 novel isothiocyanate–triazine conjugates, consisting of a 1,3,5-triazine core substituted with aliphatic or cyclic secondary amines and a phosphorus analogue of isothiocyanate [6-(isothiocyanatohexyl)phosphonate)ethyl], were synthesized with yields of 46–80%. The pharmacokinetic profiles and parameters related to Lipinski’s rule of five were determined for all compounds. All compounds were evaluated as inhibitors of acetylcholinesterase (AChE) and β-secretase (BACE1). Compound 1i showed the highest inhibitory activity against AChE (IC₅₀ = 0.182 ± 0.02 µM), while compound 1b exhibited the strongest inhibition of BACE1 (IC₅₀ = 8.48 ± 2.18 µM). To explore the potential of these multifunctional derivatives, plausible enzyme-ligand binding models were proposed based on molecular docking simulations. Full article

Background: Rapid screening of acetylcholinesterase (AChE) inhibition is essential for monitoring exposure to organophosphate compounds, particularly in field settings where access to laboratory infrastructure is limited. This study aimed to develop a portable paper-based colorimetric biosensor for the semi-quantitative detection of AChE activity in blood samples. Methods: The biosensor was based on a pH-dependent color change adapted from the modified Edson method. The platform was first optimized using experimental models and then evaluated in human capillary blood samples collected under real field conditions. Reference serum cholinesterase activity was determined by a certified clinical laboratory and used for comparison with the colorimetric response of the biosensor. RGB (red, green, and blue) image analysis was performed in a subset of samples to digitally characterize the chromatic response of the device. Results: Samples with preserved AChE activity showed a visible color shift associated with substrate hydrolysis, whereas samples with reduced or inhibited activity maintained darker blue-dominant tones. RGB analysis of human samples revealed significant associations between AChE activity and the R and G channels, supporting the ability of the platform to distinguish between chromatic patterns associated with different ranges of enzymatic activity. Conclusions: The proposed platform demonstrated the feasibility of translating a pH-based AChE assay into a portable paper-based format for semi-quantitative visual and RGB-assisted screening. Its evaluation in human samples demonstrated the feasibility of its use under field conditions as a proof-of-concept. Further studies are needed to optimize its analytical performance and validate its application in larger and more diverse populations. Full article

Microplastics (MPs) are emerging pollutants widespread in aquatic environments; however, their effects across the different life stages of aquatic organisms remain poorly understood. This systematic review integrates recent experimental results on the developmental, physiological, and neurobehavioral effects of MP exposure on zebrafish (Danio rerio), a popular model organism for ecotoxicology research. A PRISMA-guided search using Web of Science (WoS) and Scopus as databases generated 581 articles, which were screened to 60 eligible articles. The collated results showed that MP toxicity at various life stages of zebrafish was strongly related to the physicochemical properties of MPs and exposure conditions. In terms of developmental toxicity, peer-reviewed publications assessing specific MP physicochemical properties—polymer type, size, concentration, shape, and degree of aging—reported concentration-dependent effects, with increasing MP concentrations generally associated with growth inhibition, cardiac dysfunction, increased malformations, and lower hatching rate, particularly at ≥10 mg/L to ≥100 mg/L. However, several studies noted that under particle-based exposure scenarios, MP toxicity exhibited threshold-like or non-monotonic responses, attributed to aggregation, bioavailability, and uptake dynamics. Weathered and artificially aged MPs exhibited higher embryotoxicity and neurodevelopmental toxicity, including changes in gene expression of neurons, decreased integrity of motor neurons, and impaired retinal development, compared with “virgin” MPs. In terms of physiological endpoints, oxidative imbalance like changes in the activity of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)), lipid peroxidation, inflammation, and disruption of tight junctions have been reported as key toxicity pathways. Chronic MP exposure in zebrafish also caused changes in the gut microbiota, hepatic metabolism, endocrine disruption, reproductive damage, thyroid function disruption, and genotoxicity in zebrafish. In terms of neurobehavioral effects, changes in locomotor activity, anxiety response, neurotransmitter homeostasis, and acetylcholinesterase function, have been observed, in both larvae and adults, with a potentiation effect in aged MP exposure. Finally, this systematic review found major limitations for inter-study comparisons because of inconsistencies and differences in methodology applied related to MP concentration, simulation of natural MP aging, and MP dose measurements. Full article

Species of the genus Aristolochia are recognized as a rich source of structurally diverse specialized metabolites; however, the volatile chemical composition and biological properties of several Neotropical species remain poorly characterized. In particular, no information is currently available on the essential oil of Aristolochia lingulata Ule ex Pilg., which motivated this chemical, enantioselective, and preliminary biological investigation. The leaf essential oil was analyzed by GC-MS and GC-FID using nonpolar and polar stationary phases, while enantioselective GC-MS was employed to determine the distribution of selected chiral metabolites. Biological activity was evaluated through acetylcholinesterase, butyrylcholinesterase, pancreatic lipase, DPPH, and ABTS assays. A total of 57 constituents were identified and quantified, accounting for 93.5% and 91.3% of the oil on the two stationary phases. Sesquiterpene hydrocarbons and oxygenated sesquiterpenoids predominated, with dauca-5,8-diene, trans-(E)-nerolidol, β-chamigrene, β-cyclocitral, limonene, δ-amorphene, τ-muurolol, and manool among the main constituents. The oil showed moderate acetylcholinesterase inhibition (IC₅₀ = 79.8 ± 0.3 µg/mL), whereas weaker inhibition was observed against butyrylcholinesterase (IC₅₀ = 176.1 ± 3.3 µg/mL) and pancreatic lipase (IC₅₀ = 190.8 ± 9.4 µg/mL). Radical scavenging activity was also weak in the DPPH and ABTS assays (SC₅₀ = 849.7 ± 7.4 and 338.0 ± 3.9 µg/mL, respectively). Overall, this study provides the first characterization of the essential oil of A. lingulata, revealing a distinctive sesquiterpene-rich volatile profile and moderate enzyme-inhibitory activity. These findings expand the phytochemical knowledge of Neotropical Aristolochia species and provide a basis for further investigation of their bioactive constituents, mechanisms of action, and toxicological safety. Full article

Six representative small-molecule constituents were isolated and structurally characterized from the edible mushroom Tremella fuciformis: cis-oleic acid (1), 1-oleoylglycerol (2), cerevisterol (3), a cerebroside (4), trans-homoaconitic acid (5), and uridine (6). Compound 5, a tricarboxylic acid derivative, is reported for the first time as abundantly accumulated in this fungus. Aging-relevant assays showed that 1 potently inhibited α-glucosidase (IC₅₀ = 0.02 mM, surpassing acarbose) and moderately inhibited acetylcholinesterase (IC₅₀ = 0.29 mM); 5 competitively inhibited alkaline phosphatase (IC₅₀ = 5.47 mM) and suppressed GluN2A-containing NMDA receptor currents (IC₅₀ = 0.40 mM), the first such dual report for a fungal tricarboxylic acid; and 4 inhibited tyrosinase (IC₅₀ = 0.80 mM) comparably to kojic acid. HPLC confirmed meaningful recovery under mild hydro-alcoholic extraction compatible with functional food processing. These multifunctional small molecules target carbohydrate metabolism, cognition, and skin homeostasis, supporting T. fuciformis as a source of healthy-aging food ingredients. Full article

Total flavonoids (TF) from Artemisia argyi, a traditional edible-medicinal Asteraceae herb, were extracted via a food-grade ternary deep eutectic solvent (TDES, Glycerol/Levulinic Acid/Xylitol = 1:1:1 molar ratio, 30% w/w water) under ultrasound assistance. A hybrid response surface methodology–genetic algorithm–artificial neural network (RSM-GA-ANN) model optimized parameters to deliver a maximum TF yield of 107.7 mg/g—1.5–1.8-fold higher than conventional hydroalcoholic extraction. Greenness was quantified by AGREEprep (score = 0.70) and MoGAPI (score = 80/100), confirming the method’s sustainability, with TDES retaining >84% extraction efficiency over three reuse cycles. Molecular dynamics simulations revealed TDES forms a more stable hydrogen bond network with plant cell walls (average H-bond lifetime: 101.279 ps vs. 46.698 ps for 50% ethanol), a finding validated by density functional theory calculations showing TDES establishes 7–9 hydrogen bonds with cellobiose (the cellulose repeating unit), far exceeding ethanol’s 1–2 hydrogen bonds. Purified TF exhibited potent radical-scavenging activity (DPPH IC₅₀: 0.176 mg/mL; ABTS IC₅₀: 0.159 mg/mL) and multipotent enzyme inhibition (α-glucosidase IC₅₀: 55.31 μg/mL; acetylcholinesterase IC₅₀: 0.618 mg/mL; pancreatic lipase IC₅₀: 0.125 mg/mL). TF also suppressed HCT116, A549, and HepG2 proliferation (IC₅₀ ≈ 50 μg/mL) and protected HepG2 cells against H₂O₂-induced oxidative damage. As an in silico probe, the predominant quantified flavonoid eupatilin (3.64 mg/g) docked to xanthine oxidase (−7.78 kcal/mol vs. allopurinol −6.86), offering a structural hypothesis for XO interaction without attributing mixture bioactivity to a single compound. This TDES-based platform offers a scalable, green route to valorize A. argyi for functional food and nutraceutical applications. Full article

New prenylated isoindolinone alkaloids, aspernidines C-E (1–3), a new diketopiperazine alkaloid, protubonine C (4), and new polyketides, (±)-asperisocoumarin J and asperisocoumarin K (5 and 6), were isolated from the mangrove-derived fungus Aspergillus sp. SCSIO 41440, together with six known compounds (7–12). Comprehensive NMR and mass spectrometric analysis, single-crystal X-ray diffraction, and calculated electronic circular dichroism (ECD) were employed for the structural elucidation and stereochemical assignment of these compounds. All compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Compound 10 exhibited potent AChE inhibition with an IC₅₀ value of 3.16 ± 1.16 μM. Molecular docking analysis further revealed that 10 binds strongly to the AChE active site (PDB: 4EY7). These findings suggest that compound 10 represents a candidate scaffold for further investigation as an AChE inhibitor. Full article

The larvicidal and biochemical effects of Ipomoea carnea Jacq. (Convolvulaceae) methanol leaf extract against the fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae) were determined under standard laboratory conditions. The second and fourth instar larvae of S. frugiperda were fed on castor bean leaves (Ricinus communis) treated with different concentrations (1–5%) of I. carnea methanolic leaf extract. The mortality percentage significantly increased in correlation with both concentration and exposure time compared to control. Second instar larva of S. frugiperda was more susceptible to this extract than the fourth instar, with LC₅₀ values of 0.968% and 1.052%, respectively. Castor bean leaves treated with 5% extract and fed to second and fourth larval instar caused 96.3 and 92.9% larval mortality, respectively. Results from the biochemical analysis of larvae treated with I. carnea methanolic leaf extract revealed a significant reduction in total content of carbohydrate, protein and lipid compared to control. I. carnea methanolic leaf extract induced significant inhibition of acetylcholinesterase, α-esterase and β-esterase activities, alongside increase in peroxidase activity compared to the control groups. The current results are consistent with neurophysiological disruption and activation of oxidative stress in the treated S. frugiperda larvae. Therefore, we recommend I. carnea methanolic leaf extract for controlling S. frugiperda. Further field investigation into the efficacy of I. carnea methanolic leaf extract against S. frugiperda and the non-target organisms was required. Full article

Rhipicephalus microplus is a cattle ectoparasite responsible for economic losses in livestock systems. The present study aimed to evaluate the essential oil (EO) of Piper hemmendorffii and its major constituent, limonene, for their activity against R. microplus larvae. The EO of P. hemmendorffii and its major compound, limonene, were evaluated against pyrethroid-resistant R. microplus larvae using larval immersion bioassays, biochemical analyses of detoxification enzymes and acetylcholinesterase, and scanning electron microscopy (SEM). The EO showed higher larvicidal potency (LC₅₀ = 10.46 mg/mL; 95% CI: 9.86–11.09) compared to limonene (LC₅₀ = 31.62 mg/mL; 95% CI: 30.86–32.40). Piper hemmendorffii EO affected the following classes of enzymes investigated: α-Esterase (α-EST) activity increased at LC₂₅ and LC₅₀, reaching its highest level at LC₅₀, whereas β-esterase (β-EST) activity increased only at LC₂₅. Cytochrome P450 (CYP450)-associated heme content activity showed a significant increase exclusively at LC₅₀, suggesting a response of the surviving larvae to EO exposure, although this increase does not by itself demonstrate the activation of detoxification pathways. In contrast, limonene did not significantly affect the activity of the three evaluated enzymes. The inhibition of AChE by the EO suggests a possible effect on the cholinergic system, which may be associated with neurotoxic activity, whereas limonene had no significant effect. The absence of detectable ultrastructural changes by SEM suggests that treatment with either EO or limonene did not induce evident external morphological damage to the larval cuticle under the evaluated conditions. EO toxicity seems to be associated with changes in detoxification enzyme and AChE activities, suggesting the involvement of these biochemical pathways in larval response. Full article

Huperzine A (HupA) is a natural Lycopodium alkaloid known for its potent neuroprotective properties through the inhibition of acetylcholinesterase. Nevertheless, the limited understanding of its biosynthesis restricts its broader application. This study integrates full-length and second-generation transcriptomes with the quantification of HupA and its precursor, huperzine B, across various tissues of Huperzia serrata, the primary source plant. By employing phylogenetic clustering, expression profiling, and correlation analysis between gene expression and metabolite abundance, we identified 71 candidate genes from seven enzyme families potentially involved in the synthesis of the HupA backbone, including lysine/ornithine decarboxylases, copper amine oxidases (CAOs), chalcone synthases, and cytochrome P450 monooxygenases. Additionally, 28 genes from two families were identified for modification reactions, specifically 2-oxoglutarate/Fe(II)-dependent dioxygenases and caffeoyl shikimate esterases. Comparative analysis between young and mature leaves revealed 3801 genes with higher expression in young leaves, with 84 showing a high correlation with HupA content across seven families. Protein–protein interaction network analysis indicated possible interactions with transcription factors from the MYB, NF-YC, GRAS, ERF, BHLH, and SAP families. Functional validation of two candidate CAOs in planta confirmed their catalytic roles in amine/alkaloid metabolism. This study provides a theoretical foundation and a set of candidate genes for elucidating the biosynthetic pathway of HupA and related alkaloids in H. serrata. Full article

Background/Objectives: Alzheimer’s disease (AD) is a progressive, multifactorial neurodegenerative condition characterized by neurofibrillary tangles, neuronal loss, cognitive impairment, and accumulation of β-amyloid plaques. Considering the limitations of current treatments, which present adverse effects and only alleviate symptoms without modifying disease progression, there is an urgent need for new therapeutic approaches. This study aimed to investigate the neuroprotective potential of synthetic derivatives of (1E,4E)-1,5-bis[(het)aryl]penta-1,4-dien-3-ones, focusing on the inhibition of the cholinesterase enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), targets directly related to the cholinergic deficit observed in AD. Methods: The compounds were initially synthesized by aldol condensation reactions, with subsequent physicochemical characterization. They were then subjected to in silico assays that demonstrated high binding affinity to the active sites of AChE and BChE. The derivatives were evaluated in vitro for their inhibitory activity on these enzymes and in vivo in an experimental model of AD induced by streptozotocin in Wistar rats. Results: The synthesized derivatives showed favorable predicted interactions with the active sites of AChE and BChE, supporting their potential as cholinesterase inhibitors. In vitro assays demonstrated inhibitory activity against both enzymes, with selected derivatives showing improved activity compared with the parent scaffold. In the in vivo model, treatment with the selected compounds was associated with neuroprotective effects, suggesting preservation of nervous tissue integrity under AD-like conditions. Conclusions: These findings indicate that derivatives may represent promising candidates for further investigation as multitarget agents for AD. The study reinforces the relevance of integrating organic synthesis, molecular modeling, enzymatic assays, and in vivo evaluation in the search for new therapeutic strategies for neurodegenerative diseases. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that requires therapeutic agents capable of targeting multiple pathological pathways. In this study, a series of cannabidiol (CBD)-like hydrazone derivatives (3a–i) was synthesized and characterized by NMR, HRMS, and single-crystal X-ray diffraction for compound 3i. In silico ADME analysis predicted favorable drug-like properties, including compliance with Lipinski’s Rule of Five, oral bioavailability, and blood–brain barrier permeability. The compounds were evaluated for cholinesterase inhibition, antioxidant activity, cytotoxicity in neuronal cell lines, and binding interactions with human butyrylcholinesterase (hBChE) by molecular docking. Biological evaluation revealed a marked preference for BChE over acetylcholinesterase (AChE). Compound 3f was the most potent BChE inhibitor (IC₅₀ = 1.67 ± 0.11 μM), while compounds 3b and 3f demonstrated high selectivity toward BChE. Antioxidant assays (DPPH, ABTS, FRAP, and FTC) indicated moderate, mechanism-dependent activity. Compounds 3b and 3e showed the strongest ABTS radical-scavenging effects, whereas compounds 3b and 3f provided the greatest protection against lipid peroxidation, surpassing CBD under the tested conditions. Several derivatives, particularly 3a, 3b, 3f, 3h, and 3i, exhibited favorable safety profiles in SH-SY5Y and Neuro-2a cells. Molecular docking supported the experimental findings. Overall, compounds 3b and 3f emerged as promising multifunctional leads for the development of multitarget-directed anti-Alzheimer agents. Full article

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with limited effective therapies. In this study, a series of 2-(arylamino)thiazol-4(5H)-one derivatives was synthesized using an efficient microwave-assisted protocol, and evaluated for neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced oxidative stress (OS) in SH-SY5Y neuronal cells and an Aβ42-expressing Drosophila melanogaster model of AD. Among the synthesized compounds, 3n, 3i, and 3b exhibited low cytotoxicity and significant neuroprotection, as evidenced by increased cell viability, reduced reactive oxygen species (ROS) production, and preserved mitochondrial membrane potential. Notably, compound 3n demonstrated the highest activity and effectively ameliorated Aβ42-induced behavioral deficits in vivo. Molecular docking studies predicted favorable binding affinity within the acetylcholinesterase (AChE) active site, with the thiazol scaffold and aryl substituents stabilizing ligand binding through π–π stacking and hydrophobic interactions; compound 3n also formed additional hydrogen bonds enhancing its affinity. Consistent with the docking predictions, in vitro AChE inhibition studies demonstrated that compounds 3n, 3i, and 3b inhibited AChE in a concentration-dependent manner. Network pharmacology predicted seven potential core targets implicated in AD pathogenesis and related pathways, including OS, neuroinflammation, and synaptic dysfunction. Furthermore, in silico pharmacokinetic analysis indicated compliance with Lipinski’s and Veber’s rules, supporting favorable drug-like properties. While further experimental validation is essential, these findings highlight 2-(arylamino)thiazol-4(5H)-one derivatives, particularly compound 3n, as promising multifunctional candidates for further preclinical development against AD. Full article