Search Results (2,028)

Conventional plastics are widely utilised across industrial sectors and in consumer products. However, the growing use of plastics has led to plastic pollution, including the formation of nanoplastics (NPs), which are harmful to aquatic organisms. Bioplastics are emerging alternatives. They are renewable and/or biodegradable and are supposed to be more environmentally friendly. However, the toxicity and environmental fate of bioplastics are not yet fully understood. This study evaluated the toxicity and fate of commercially available plain or fluorescent polylactic acid (PLA) NPs (250 nm) on aquatic organisms. Confocal microscopy demonstrated the uptake of fluorescent PLA NPs by the test organisms, marine rotifers (Brachionus plicatilis), brine shrimps (Artemia salina) and zebrafish (Danio rerio) embryos. However, the results of the bioassays indicate that plain PLA NPs did not induce acute toxicity in either of the two zooplankton species and did not cause substantial mortality, malformations, or hatching delays in zebrafish embryos at the tested concentrations (up to 100 mg/L). However, brine shrimp showed a significant decrease in ingestion capability. The biochemical biomarkers, catalase activity induction, as an indicator of oxidative stress, and acetylcholinesterase inhibition, as a marker of neurotoxicity, showed no significant alterations compared to the control of both zooplankton species and that of zebrafish embryos. Overall, the findings suggest a pattern of no acute and low sublethal toxicity for the tested plain PLA NPs in the studied organisms. Nonetheless, further research is imperative to comprehensively assess the environmental fate of bioplastics found in various consumer products, as these may contain harmful chemical additives, as well as the effects of prolonged exposure and their impact on physiological parameters, ensuring informed decisions before their widespread commercialisation and presence in the environment. Full article

Lymantria dispar larvae were used as a model to study the effects of sublethal chronic dietary aluminum exposure at concentrations of 50, 250, 500, and 1000 μg Al/g dry food (T1, T2, T3, and T4, respectively) on fitness traits, acetylcholinesterase (AChE) activity, and locomotion. At the lowest concentration, the greatest reduction in mass and AChE activity, as well as an increase in travel distance and time in movement, was observed relative to the control group. Strong positive correlations between larval mass and time in movement were observed in T1. AChE activity correlated positively with larval mass and relative growth rate (RGR) and negatively with locomotion parameters. An increase in relative growth rate led to a decrease in locomotion parameters (250, 500, and 1000 μg Al/g dry food). As the amount of metal increased, there was a trend towards a decrease in locomotion, and the value was observed to approach the control value. This study suggests that aluminum has an influence on the fitness characteristics, AChE activity, and locomotion of L. dispar larvae. The results obtained allow us to better understand the toxicity of aluminum and, at the same time, underline the need for further studies involving insects. Full article

Herbicide glyphosate and its main metabolite, aminomethylphosphonic acid (AMPA), have raised concerns due to their potential neurotoxicity in non-target aquatic species. This study evaluated neurotoxic effects in common carp (Cyprinus carpio) following a 28-day dietary exposure to glyphosate (325.2 and 3310.0 μg/kg) and AMPA (335.2 and 3441.0 μg/kg) at two concentrations, including control and four treatment groups. Brain acetylcholinesterase activity was significantly (p < 0.05) reduced in all exposed groups, while muscle acetylcholinesterase activity remained unchanged. Brain dopamine was significantly (p < 0.05) decreased only in the highest AMPA group. Plasma butyrylcholinesterase activity increased significantly (p < 0.05) in the low-dose glyphosate group. The level of mRNA expression of ache was significantly (p < 0.05) downregulated in the brain across all treatments and upregulated in the gills only at the highest AMPA concentration. Histological analysis of the brain revealed vascular congestion in both glyphosate-exposed groups, indicating pathological changes. These results suggest that dietary exposure to glyphosate and AMPA can affect cholinergic and dopaminergic pathways in fish, with the brain being a particularly sensitive target tissue. Our findings contribute to understanding the potential neurotoxic risks posed by glyphosate-based compounds in aquatic environments. Full article

Schizaphis graminum is the most important pest of wheat, and its feeding harm not only affects photosynthesis but also causes diseases, posing a serious threat to wheat production. We measured the contact killing and fumigation activities, population changes, enzyme activities, and nanoemulsion physicochemical property of Eupatorium fortune essential oil (EFEO) and pyrethrin against S. graminum and its natural enemy (Harmonia axyridis). Toxic effects of EFEO and pyrethrin increased with increasing concentration. After 24 h of contact killing, the LD₅₀ of S. graminum were 9.23 and 0.02 μg/head, respectively. Harmonia axyridis were 36.71 and 0.07 μg/head. The fumigation of EFEO LD₅₀ on S. graminum was 9.779 mg/L (y = 2.88x − 2.852). EFEO contains 28 chemical components, including l-Caryophyllene, Lily aldehyde, α-Terpineol, and Cineole. EFEO LD₅₀ significantly reduced the adult longevity, nymph production, and nymph production duration of the F0 S. graminum, while there were no significant differences in various parameters of offspring. The activity of acetylcholinesterase, glutathione-S-transferase, and carboxylesterase is significantly affected. The population decline rate of EFEO nanoemulsion is significantly higher than that of EFEO. This research aims to clarify the toxic effect of EFEO on S. graminum, providing a scientific basis for developing new plant essential oil preparations and nano preparations. 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

Control of Aedes aegypti, the primary vector of arboviruses such as dengue, Zika, and chikungunya, is increasingly difficult due to resistance to synthetic insecticides and environmental concerns. Plant essential oils offer sustainable alternatives with multi-target modes of action and rapid biodegradation. This study evaluated the insecticidal potential of the essential oil of Aniba canelilla (EOANIB), its major constituent 1-Nitro-2-phenylethane (NFTANE), and the derivative 1-Nitro-2-phenylethene (NFTENE) against larvae and adults of A. aegypti. Acetylcholinesterase (AChE) inhibition was quantified using enzymes from Electrophorus electricus, Aedes aegypti and Drosophila melanogaster. Pluronic^® F127 (5% w/v) nanoformulations loaded with EOANIB, NFTANE, or NFTENE at 1.5% or 0.34% (w/v) improved efficacy and stability. Formulations remained stable for 120 to 190 days at 25 to 60 °C. Larvicidal assay at 24 h yielded LC₅₀ values of 86.9 (CI 78.2–94.7) ppm for EOANIB, 84.8 ppm (CI 75.6–92.4) for NFTANE and 10.9 (CI 8.0–14.0) ppm for NFTENE. Against adults, EOANIB achieved an LC₅₀ of 33.9 ppm at 1.5 h. Nanoformulation reduced the EOANIB LC₅₀ by 22.2% after 24 h and 40.1% after 48 h. Toxicity assays evaluated selectivity with Artemia salina (EOANIB LC₅₀: 77.2 ppm) and no mortality in D. melanogaster at 100 ppm. The convergence of efficacy, formulation-enhanced performance, and demonstrated storage stability positions Aniba canelilla as a promising source of bioinsecticide candidates for Aedes aegypti control and supports further development of micellar delivery systems for integrated vector management. Full article

The sustainable management of winery residues could represent a cornerstone for promoting environmental and economic sustainability from a circular economy perspective. In this context, our study aimed to evaluate Vitis vinifera L. ‘Nero di Troia’ cultivar grape pomace as a valuable waste product for the cultivation of Pleurotus mushroom, in comparison with traditional wheat straw-based cultivation. Mushroom extracts were prepared through the eco-friendly microwave-assisted extraction technique, using green solvents with different polarity degrees. Total protein content, total polyphenol content, and antioxidant activity (FRAP and DPPH assays) were assessed for the water and EtOH hydrophilic extracts. Grape pomace often gave higher values than wheat straw, especially for the P. eryngii var. eryngii water extract protein content, which was 3.5-fold higher (0.68 ± 0.14 mg BSA/mL and 0.192 ± 0.025 mg BSA/mL, respectively). The ethyl acetate extracts of both mushroom species gave biologically relevant results in terms of inhibiting activity against acetylcholinesterase, an enzyme involved in the pathogenesis of Alzheimer’s disease (50% inhibitory activity at concentrations ≤ 1.5 mg/mL), thus paving the way for more in-depth investigation. The extract’s metabolic profile was investigated through GC-MS analysis. The results show that incorporating grape pomace into mushroom production represents a concrete step toward more sustainable biotechnological processes. Full article

Sea mayweed (Tripleurospermum maritimum L. syn. Matricaria maritima) is a halophytic species widely distributed along the Atlantic shoreline. Unlike other Tripleurospermum species, the chemical composition and biological activities of this halophyte have received no attention. Here, a hydroalcoholic extract of sea mayweed leaves was evaluated for in vitro antioxidant (DPPH, ABTS, and FRAP bioassays), anti-inflammatory (NO reduction in RAW 264.7 macrophages), anti-diabetic (alpha-glucosidase inhibition), neuroprotective (inhibition of acetylcholinesterase), and skin protective (tyrosinase, melanogenesis, elastase, and collagenase inhibition) activities. Solid–liquid partition chromatography of the extract and NMR characterization of its fractions allowed the identification of some major compounds, including fructo-oligosaccharides in the MeOH_20% fraction, a new carbohydrate called tripleurospermine (1), 3-5-dicaffeoylquinic acid (2) in the MeOH_40% fraction, and matricaria lactone (3) in the MeOH_80% fraction. MeOH₄₀ fraction exhibited strong antioxidant, anti-tyrosinase (thus skin-whitening potential), and anti-glycosidase activities (anti-diabetic potential), whereas MeOH_80% fraction showed anti-inflammatory and anti-diabetic potential. Overall, our results suggest that sea mayweed may have dietary or medicinal uses due to its biochemical composition and bioactivities. Full article

Essential oils from the genus Piper are recognized for their chemical diversity and biological potential, yet Piper platylobum has been scarcely investigated. This study aimed to characterize the chemical composition of the leaf essential oil of P. platylobum and evaluate its antimicrobial, antioxidant, and anticholinesterase activities. The oil was obtained by steam distillation and analyzed through gas chromatography–mass spectrometry (GC-MS) and gas chromatography equipped with a flame ionization detector (GC-FID), leading to the identification of 35 compounds that accounted for 91.11% of the volatile fraction. Dillapiole (42.0%) was the principal constituent, followed by α-(E)-bergamotene (5.69%), (E)-caryophyllene (5.01%), and (E)-isocroweacin (3.75%). Biological assays revealed selective antimicrobial activity, with inhibition observed only against Enterococcus faecium (MIC = 1000 µg/mL), while no effect was detected against other bacterial or fungal strains tested. Antioxidant evaluation showed moderate activity in the ABTS assay (SC₅₀ = 335.71 ± 1.43 µg/mL; TEAC = 45.85 ± 1.68 µM Trolox/g EO), but no activity in the DPPH assay. The essential oil also displayed moderate inhibition of acetylcholinesterase (IC₅₀ = 76.86 ± 1.00 µg/mL), suggesting a potential role in neuroprotective applications. This study constitutes the first report on the chemical composition and biological activities of P. platylabum essential oil, highlighting its potential as a novel source of bioactive compounds. Full article

Acetylcholinesterase (AChE) inhibitors are the primary target for single-molecule anti-Alzheimer’s disease (AD) therapeutics. Though AChE has historically been the focus of investigation for small-molecule inhibitors, interest in another cholinergic enzyme, butyrylcholinesterase (BChE), has grown in recent years. Attention stems from BChE’s role in β-amyloid (Aβ) protein aggregation and an increase in BChE concentration during the late stages of AD, where a decrease in AChE concentration is also observed. Currently, five FDA-approved drugs are on the market for inhibiting AChE, though no BChE-selective drugs have been approved so far. In this review, we focus on newly identified BChE selective inhibitors and present the ideas behind these discoveries. Full article

This study investigates the neuroprotective and anxiolytic effects of Solanum macrocarpon L. leaf n-butanol extract (SMB) in a zebrafish model of scopolamine (SCOP; 100 μM)-induced cognitive and behavioral impairments. SCOP, a muscarinic receptor antagonist, is commonly used to mimic memory deficits and anxiety-like behaviors associated with neurodegenerative conditions. Zebrafish were chronically exposed to SMB at concentrations of 1, 3, and 6 mg/L. Behavioral assessments included anxiety-related paradigms, such as novel tank diving (NTT), novel approach (NA), and light–dark transition (LD) tests, as well as cognitive assays, including the Y-maze and novel object recognition (NOR) tests. SMB significantly mitigated SCOP-induced anxiety-like behaviors and cognitive deficits in a dose-dependent manner. Biochemical analyses demonstrated that SMB inhibited acetylcholinesterase (AChE) overactivity, indicating restoration of cholinergic function. Furthermore, SMB enhanced the activity of endogenous antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) and significantly reduced oxidative stress biomarkers, including malondialdehyde (MDA) and protein carbonyls. These findings suggest that SMB may exert neuroprotective effects through modulation of cholinergic signaling and oxidative stress. Overall, SMB represents a promising phytotherapeutic candidate for mitigating cognitive and anxiety-related symptoms linked to oxidative damage. Further investigations are warranted to characterize its active constituents and assess long-term efficacy and safety in models of neurodegeneration. Full article

The cholinergic system is one of the most ancient and widespread signaling systems in the body, implicated in a range of pathological conditions—from neurodegenerative disorders to cancer. Given its broad relevance, there is growing interest in characterizing this system across diverse cellular models to enable drug screening, mechanistic studies, and exploration of new therapeutic avenues. In this study, we investigated four cancer cell lines: one of neuroblastoma origin previously used in cholinergic signaling studies (SH-SY5Y), one non-small cell lung adenocarcinoma line (A549), and two small cell lung carcinoma lines (H69 and H82). We assessed the expression and localization of key components of the cholinergic system, along with the cellular capacity for acetylcholine (ACh) synthesis and release. Whole-cell flow cytometry following membrane permeabilization revealed that all cell lines expressed the ACh-synthesizing enzyme choline acetyltransferase (ChAT). HPLC-MS analysis confirmed that ChAT was functionally active, as all cell lines synthesized and released ACh into the conditioned media, suggesting the presence of autocrine and/or paracrine ACh signaling circuits, consistent with previous reports. The cell lines also demonstrated choline uptake, indicative of functional choline and/or organic cation transporters. Additionally, all lines expressed the ACh-degrading enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), as well as the alfa seven (α7) nicotinic and M1 muscarinic ACh receptor subtypes. Notably, flow cytometry of intact SH-SY5Y cells revealed two novel findings: (1) ChAT was localized to the extracellular membrane, a feature not observed in the lung cancer cell lines, and (2) BChE, rather than AChE, was the predominant membrane-bound ACh-degrading enzyme. These results were corroborated by both whole-cell and surface-confocal microscopy. In conclusion, our findings suggest that a functional cholinergic phenotype is a shared feature of several carcinoma cell lines, potentially serving as a survival checkpoint that could be therapeutically explored. The discovery of extracellular membrane-bound ChAT uniquely in neuroblastoma SH-SY5Y cells points to a novel form of in situ ACh signaling that warrants further investigation. Full article

Highly degraded sterols belonging to the incisterol group have been identified in a large set of microorganisms. The leading product in the family is demethylincisterol A3 (DM-A3), isolated from various fungi and endowed with marked antitumor properties. Since the initial discovery of incisterol from a marine sponge in the 1990s, more than 30 incisterol-type natural products have been identified, essentially from fungi. An overview of these products, their bio-origin, chemical synthesis, and associated pharmacological properties is presented. The series includes diverse incisterol and demethylincisterol derivatives, chaxines, volemolide, different analogues (salimyxins, phellinignincisterols, daedatrin D, inonotoide F, aplykurodinone-1, dendrodoristerol), and a glycoside derivative (xyloneside), all bearing a tetracyclic incisterol framework. An analysis of the anticancer mechanism of the action of DM-A3 underlined the three main components of its activity associated with the (i) inhibition of β-catenin and the Wnt signaling pathway, (ii) inhibition of tyrosine phosphatase SHP2 (IC₅₀ = 6.75 µM) implicated in cancer cell survival and differentiation, and (iii) blockade of α7nAchR activation coupled with inhibition of acetylcholinesterase (IC₅₀ = 11.16 µM). A comprehensive picture of the DM-A3 mechanism of action is discussed, highlighting the uniqueness of the compound as a dual SHP2/AchE inhibitor able to attenuate an inflammatory response through the cholinergic anti-inflammatory pathway. The review shed light on this little-known category of incisterol-type natural products, with the objective of promoting further research into this neglected group of anticancer agents. Full article

Chlorpyrifos (CHP) is a persistent organophosphate pesticide whose presence in water poses serious ecological and health risks. Here, we report a sustainable adsorbent obtained by high-temperature carbonization of immature walnuts (Juglans regia). The adsorbent’s structure, surface chemistry, and charge properties were comprehensively characterized using FTIR, SEM-EDX, zeta potential measurement, BET analysis, and XPS. The synthesis yielded a mesoporous carbon material with a BET surface area of 303 m² g⁻¹. Its performance in CHP removal was assessed under batch and dynamic conditions. Adsorption followed pseudo-second-order kinetics (k₂ = 0.122 mg min⁻¹ g⁻¹; contact time 0–120 min). Isotherm experiments performed at 20, 25, and 30 °C, with equilibrium data best described by the Langmuir and Sips models, reaching a maximum capacity of 43.2 mg g⁻¹. Thermodynamic analysis indicated a spontaneous and endothermic process. The adsorbent demonstrated selectivity for CHP over chlorpyrifos-oxon (CPO) in binary mixtures, retained its efficiency over at least ten regeneration cycles with ethanol, and removed up to 90% of CHP toxicity, as measured by acetylcholinesterase inhibition. Dynamic filtration confirmed its applicability under flow conditions. These findings demonstrate that the investigated adsorbent is an effective, reusable, and selective adsorbent, offering a low-cost and eco-friendly approach to pesticide removal from contaminated waters. Full article

Fulfilling the demand for functional food with cost safety and environmental sustainability, our novel anthocyanin-enriched functional drink containing the purple waxy corn cob-derived functional ingredient “MP1” showed cognitive enhancing effects with safety in bilaterally ovariectomized rats, a validated model of menopause. Since no clinical evidence that confirms the mentioned effect was available until now, we conducted a two-arm, randomized, double-blind, placebo-controlled, crossover study to confirm the benefits mentioned above. A total of 32 menopausal participants were divided into placebo and MP1 (400 mg) groups, and were subject to a 2-month study period. Safety parameters, working memory and brain components, especially N100 and P300, the negative and positive potentials derived from the event-related potential (ERP) which indicated attention and cognitive processing, together with oxidative stress markers acetylcholinesterase (AChE) and monoamine oxidase (MAO), were assessed at baseline and every month. No serious side effects or toxicity signs were observed. Subjects who consumed MP1 also had decreased N100 and P300 latency, improved working memory and decreased oxidative stress status. Therefore, a byproduct of purple corn can successfully serve as a novel functional ingredient for developing a cognitive enhancer drink with the qualities of safety, cost reduction, and environmental sustainability promotion. Full article