Acetylcholinesterase Activity Research Articles

Perturbation of Enzyme Structure by nano-Metal Organic Frameworks: A Question Mark on their Safety-by-Design?

Our study investigates the interactions between nanoscale Metal-Organic Frameworks (nMOFs), specifically ZIF-8 and CuIm, and key enzymes: Acetylcholine Esterase (AChE), α-amylase. Using circular dichroism (CD) spectroscopy, we observed significant alterations in the secondary structures of these enzymes upon interaction with nMOFs. AChE showed a reduction in α-helix content from 20.1% to a significantly lower value when exposed to 160µg/mL of nMOFs, with a corresponding increase in β-sheet and other structural components. Enzymatic activity assays revealed that CuIm nMOFs decreased AChE activity by 67.08% at the highest concentration tested (160µg/mL). ZIF-8 also affected AChE activity significantly at this concentration. Similarly, α-amylase exhibited structural changes, with increasing concentrations of nMOFs leading to a near-total loss of secondary structure at 80 and 160µg/mL. These structural changes were accompanied by a marked decrease in enzymatic activity, particularly with CuIm nMOFs showing the most substantial inhibitory effects. Our findings highlight the profound impact of nMOFs on enzyme structure and function, emphasising the need for comprehensive assessments of nMOFs' potential toxicity and understanding the aspects of their safety-by-design.

Neuroprotective Effects of Curcumin against Chronic Chlorpyrifos- Induced Oxidative Damage in Rat Brain Tissue.

Chlorpyrifos (CPF) is an organophosphate pesticide that inhibits acetylcholinesterase (AChE) activity. Investigations have also focused on its neurotoxicity, which is independent of AChE inhibition. Here, we evaluated the effect of CPF on oxidative indices in the brain tissue and explored the protective effect of curcumin (Cur) against its toxicity. Forty male Wistar rats were divided into five groups, each consisting of eight rats (n = 8) per group. Animals were administrated by oral gavage for 90 days with the following treatments: control (C), CPF, CPF + CUR 25 mg/kg, CPF + CUR50, and CPF + cur 100 received olive oil, CPF, CPF plus 25 mg/kg of CUR, CPF plus 50 mg/kg of CUR, and CPF plus 100 mg/kg of CUR, respectively. After anesthetization, animal brain tissues were obtained for assessment of oxidative stress indices. The concentration of MDA significantly increased in the brains of the CPF group as compared to the control group (p < 0.01). Also, a significant decrease in MDA concentrations was observed in the brains of rats in the CPF + Cur 100 group compared to the CPF group (p < 0.05). A significant decrease was noted in the GSH concentration in the brains of the CPF group compared to the control group (p < 0.05). Treatment with Cur at 100 mg/kg exhibited a significant increase in GSH concentrations in the brains of the CPF-exposed group compared to the CPF group without Cur administration (p < 0.05). The concentration of NO exhibited a significant increase in the brains of the CPF group when compared to the control group (p < 0.05). Also, a significant decrease in NO concentration was observed in the brain tissue of the CPF + Cur 100 group compared to the CPF group (p < 0.05). Our data establish that chronic exposure to CPF induced oxidative stress in brain tissue, which was reversed by CUR administration. Additional experimental and clinical investigations are needed to validate the efficacy of CUR as a potential antidote for CPF poisoning.

Assessing the therapeutic potential of KK14 peptide derived from Cyprinus Carpio in reducing intercellular ROS levels in oxidative Stress-Induced In vivo zebrafish larvae model: An integrated bioinformatics, antioxidant, and neuroprotective analysis.

H2O2 is a significant reactive oxygen species (ROS) that hinders redox-mediated processes and contributes to oxidative stress and neurodegenerative disorders. Oxidative stress causes impairment of cell macromolecules, which results in cell dysfunction and neurodegeneration. Alzheimer's disease and other neurodegenerative diseases are serious conditions linked to oxidative stress. Antioxidant treatment approaches are a novel and successful strategy for decreasing neurodegeneration and reducing oxidative stress. This study explored the antioxidant and neuroprotective characteristics of KK14 peptide synthesized from LEAP 2B (liver-expressed antimicrobial peptide-2B) derived from Cyprinus carpio L. Molecular docking studies were used to assess the antioxidant properties of KK14. The peptide at concentrations 5-45 μM was examined by using in vitro and in vivo assessment. Analysis was done on the developmental and neuroprotective potential of KK14 peptide treatment in H2O2-exposed zebrafish larvae which showed Nonlethal deformities. KK14 improves antioxidant enzyme activity like catalase and superoxide dismutase. Furthermore, it reduces neuronal damage by lowering lipid peroxidation and nitric oxide generation while increasing acetylcholinesterase activity. It improved the changes in swimming behavior and the cognitive damage produced by exposure to H2O2. To further substantiate the neuroprotective potential of KK14, intracellular ROS levels in zebrafish larvae were assessed. This led to a reduction in ROS levels and diminished lipid peroxidation. The KK14 has upregulated the antioxidant genes against oxidative stress. Overall, this study proved the strong antioxidant activity of KK14, suggesting its potential as a strong therapeutic option for neurological disorders caused by oxidative stress.

Effects of glyphosate based herbicide exposure in early developmental stages of Physalaemus gracilis

The impact of environmental pollutants has been a focus of investigation in recent years. Studies assessing the effects of these pollutants are essential for understanding the challenges faced by non-target species. Among the many substances used for agricultural purposes, the herbicide glyphosate is one of the most widely marketed in recent years. This broad-spectrum herbicide is commonly used to protect a variety of crops. In this study, we evaluated the effects of chronic glyphosate exposure on a native amphibian species, Physalaemus gracilis. Amphibians, which develop in aquatic environments, are highly sensitive to pesticides. Because of this, we investigated morphological, physiological, behavioral, and biochemical parameters in the early stages of development. The animals were exposed to environmentally relevant concentrations of a glyphosate-based herbicide (0, 100, 350, and 700 µg L⁻¹) during their first seven days of life. As a result, we observed impairments in anti-predatory behavior, reduced body mass index, and scaled mass index, malformations of the mouth and intestine, increased acetylcholinesterase activity, cardiotoxicity, and oxidative stress. These findings underscore the importance of studying native non-target species and highlight the need to evaluate the effects of environmentally relevant concentrations, as well as to review legislation regarding permissible levels of glyphosate in surface water and public water supplies.

Effects of diuron and two of its metabolites in biochemical markers and behavior of zebrafish larvae.

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is an herbicide used in many crops, including sugar cane cultivation. It is commonly found in aquatic ecosystem and is of high concern due to its ability to persist in the environment. Diuron metabolites include DCA (3,4-dichloroaniline) and DCPMU (3-(3,4-dichlorophenyl-1-methylurea). The objective of this study was to evaluate the effects of diuron and two of its metabolites in zebrafish (Danio rerio) developing embryos, from biochemical to individual level. Activities of the enzymes acetylcholinesterase (AChE), catalase (CAT), glutathione-S-transferase (GST), andlactate dehydrogenase (LDH) and the levels of lipid peroxidation (LPO), swimming activity, and body length were investigated after an exposure of 120h, and the heart rate was determined after 48h of exposure. The range of concentrations tested was 0.003-3.000mg/L diuron, 0.020-1.500mg/L DCA, and 0.020-2.100mg/L DCPMU. Results showed that AChE activity was inhibited by diuron (3.000mg/L) and DCPMU (0.326, 0.828mg/L). However, the swimming activity of fish larvae exposed to diuron or its metabolites was not affected. The CAT was induced by DCPMU, and GST was induced by diuron. This suggests that CAT is acting to cope with oxidative stress induced by DCPMU and GST might have a role in the detoxification of diuron. In addition, larvae exposed to DCA (0.633 and 1.500mg/L) had a reduction in their length, and larvae exposed to diuron (0.754 and 3.000mg/L) and DCA (0.267, 0.633, and 1.500mg/L) presented bradycardia, suggesting cardiotoxicity. Overall, results indicate that diuron, DCA, or DCPMU induces adverse effects during the early phases of zebrafish development, such as the impairment of neurotransmission and cardiovascular function and alterations in antioxidant enzymes and growth. Diuron appeared as more toxic than its metabolites since the lowest LOEC (0.012mg/L) and higher integrated biomarker response (IBR) values were obtained with exposure to this herbicide. Furthermore, as it is fast degraded into DCA and DCPMU, which also affected the zebrafish developing embryos at environmentally relevant concentrations, its use might be of concern in ecosystems that receive agriculture runoff due to their potential adverse effects to aquatic biota.

Sinulariapeptide F, a new peptide from culture broth of marine-derived fungus Simplicillium sp. SCSIO 41222.

One new compound named sinulariapeptide F (1) together with one known butyrolactone (2) and seven known peptides (3-9) were isolated from the fungus Simplicillium sp. SCSIO 41222. Their structures and absolute configurations were established using HRESIMS, NMR spectroscopy (1H, 13C, HSQC, HMBC) and marfey's method. All of these compounds were assessed their inhibitory activity of acetylcholinesterase (AChE) and pancreatic lipase (PL). Compounds 4 and 6 were selected to test for the inhibitory activity against programmed cell death-1 (PD-1)/ programmed cell death-ligand 1 (PD-L1). The results indicated that compound 4 displayed potent inhibition activity against PD-1/ PD-L1 with an IC50 value of 0.656 μM. Furthermore, the docking analysis demonstrated the interactions between 4 and proteins, suggesting PD-L1 to be a probable target for compound 4.

Neurotoxicity, Cytotoxicity, and Genotoxicity of Phyto-radio Synthesized Selenium Nanoparticles in Culex pipiens Complex.

Effective mosquito management strategies are crucial to minimize the number of mosquito-borne diseases. Selenium nanoparticles (SeNPs) are promising in mosquito control because they are effective and eco-friendly rather than synthetic insecticides. The current study was conducted to evaluate the impact of SeNPs on the detoxification enzymes, acetylcholine esterase (AChE), glutathione S-transferase (GST), and α-carboxyl esterase (α-CarE), in larval instars of Culex pipiens complex at the LC50 concentration. In 3rd instar larvae treated with microwave-assisted selenium nanoparticles (SeNPs-MW) and gamma-assisted selenium nanoparticles (SeNPs-G), it was found that AChE activity was significantly inhibited. On the other hand, significant increases in GST and α-CarE activities were observed. Additionally, genotoxic and ultrastructure studies of midgut epithelial cells in 3rd instar larvae revealed DNA damage and cell lysis, including destruction of the cell membrane, microvilli, and nuclei. These findings suggest that SeNPs have an adverse effect on AChE gene expression, resulting in its downregulation. This downregulation can be attributed to the formation of reactive oxygen species induced by SeNPs that can modulate the host defense mechanism leading to apoptosis and subsequent larval mortality. The present study was the first to use phyto-microwave-assisted and gamma-assisted synthesis of SeNPs which provides an eco-friendly and cost-effective solution to reduce the risk of chemical insecticides. Furthermore, an integrated pest management program (IPM) using nanocides can be successfully developed for mosquito control.

Biomarkers of Pesticide Exposure in a Traditional Brazilian Amazon Community

In 2008, Brazil became the country with the highest pesticide use in the world, with over one billion liters of pesticides applied to crops in 2009. The impacts of these products on public health are wide-ranging. Vast territories are affected, involving different population groups, such as workers in various fields of activity, the population that consumes contaminated food, and people living around factories, such as traditional communities. This study aimed to assess human exposure to pesticides through epidemiological and laboratory data of residents of the Santo Antônio quilombola community in Concórdia do Pará, Amazon region, Brazil. Epidemiological data were collected using a semi-structured questionnaire, which included factors such as sex, age, length of residence, and level of exposure to pesticides. The modified Ellman method was used to assess the activity of cholinesterases, and flow cytometry was performed for cytokine analysis. Analysis of collected blood samples showed that, in most cases, there was no significant reduction in the activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) compared to other studies in the scientific literature. Meanwhile, there was an increase in the levels of IFN-γ cytokines, especially IL-6, in all groups. The findings of this study highlight the urgent need for a comprehensive monitoring program, considering that some conditions other than pesticide exposure can alter the activities of the biomarkers used in this study.

Metformin Mitigates Trimethyltin-Induced Cognition Impairment and Hippocampal Neurodegeneration

The neurotoxicant trimethyltin (TMT) triggers cognitive impairment and hippocampal neurodegeneration. TMT is a useful research tool for the study of Alzheimer's disease (AD) pathogenesis and treatment. Although the antidiabetic agent metformin has shown promising neuroprotective effects, however, its precise modes of action in neurodegenerative disorders need to be further elucidated. In this study, we investigated whether metformin can mitigate TMT cognition impairment and hippocampal neurodegeneration. To induce an AD-like phenotype, TMT was injected i.p. (8 mg/kg) and metformin was administered daily p.o. for 3 weeks at 200 mg/kg. Our results showed that metformin administration to the TMT group mitigated learning and memory impairment in Barnes maze, novel object recognition (NOR) task, and Y maze, attenuated hippocampal oxidative, inflammatory, and cell death/pyroptotic factors, and also reversed neurodegeneration-related proteins such as presenilin 1 and p-Tau. Hippocampal level of AMP-activated protein kinase (AMPK) as a key regulator of energy homeostasis was also improved following metformin treatment. Additionally, metformin reduced hippocampal acetylcholinesterase (AChE) activity, glial fibrillary acidic protein (GFAP)-positive reactivity, and prevented the loss of CA1 pyramidal neurons. This study showed that metformin mitigated TMT-induced neurodegeneration and this may pave the way to develop new therapeutics to combat against cognitive deficits under neurotoxic conditions.

Inhibition Effects of Some Non-Proteinogenic Amino Acid Derivatives on Carbonic Anhydrase Isoenzymes and Acetylcholinesterase: An In Vitro Inhibition and Molecular Modeling Studies.

Amino acid derivatives are molecules of interest for medicinal chemistry and drug design studies due to their important chemical properties. In this study, the inhibition effects of some non-proteinogenic amino acid derivatives (hippuric acid (A), N-(9-Fluorenylmethoxycarbonyl)-D-valine (B), N-Z-(1-Benzotriazolylcarbonyl) methylamine (C), (S)-N-Z-1-Benzotriazolylcarbonyl-2-phenylethylamine (D)) on carbonic anhydrase I (hCA-I), II (hCA-II) isoenzymes and acetylcholinesterase (AChE) activity, whose inhibitors are of vital pharmacological importance, were examined. While carbonic anhydrase (CA) inhibitors are effective molecule candidates for the treatment of many diseases from glaucoma to cancer, acetylcholinesterase inhibitors are target molecules for the treatment of Alzheimer's disease. According to the results of this study, compound D had a strong inhibitory effect on hCA-I (IC50: 0.836 μM) and hCA-II (IC50: 0.661 μM), while compound B (IC50: 100 μM) showed a strong inhibitory effect on AChE activity. In addition, inhibition results were supported by molecular modeling studies. We hope that the obtained results will contribute to the synthesis of new and effective amino acid derivative inhibitors for CA and AChE.

A novel portable in situ analyzer for highly sensitive monitoring of organophosphorus and carbamate pesticides in food and environment

The presence of excessive residues of organophosphorus (OPs) and carbamate (CPs) pesticides in food and the environment poses a significant threat to human health and ecological sustainability. Herein, we reported a dual-readout, portable, and highly sensitive photoelectric analyzer (DPHP-analyzer) to achieve rapid and accurate monitoring of OPs and CPs. The dual signal strategy is mainly achieved by controlling the activity of acetylcholinesterase (AChE) in the presence of OPs to catalyze acetylthiocholine (ATCh) and generate thiocholine (TCh), which specifically induced the conversion of colorless Ellman's reagent (DTNB) into yellow 5-thio-2-nitrobenzoic acid (TNB). Simultaneously, the utilization of positively charged TNB as an absorber can induce a dynamic fluorescence quenching effect based on energy transfer mechanism. Fully cooperating with the above mechanism, a CD like, disposable array-based chip manufactured by 3D printing (CD-AN-chip) was designed and integrated to deliver reagents. By use of this dual-output strategy, the analyzer and chip can provide good sensitivity and selectivity for the monitoring of diazinon and carbendazim (case analysis) with a LOD 0.38 ng/mL for carbendazim. And the reproducibility, stability and practicability analysis of real sample have been thoroughly validated simultaneously. Importantly, with the features of fluorescence fingerprint map, the detector could be employed for the distinction of various analytes and further be used for monitoring the nutritional environment within residential and public settings.

Nitric Oxide-Dependent Regulation of Oxygen-Related Processes in a Rat Model of Lead Neurotoxicity: Influence of the Hypoxia Resistance Factor

Background/Aims: Lead exposure is known to induce oxidative stress and neurotoxicity. Nitric oxide (NO) plays an important role in modulating oxidative stress, with L-arginine as a precursor of NO and Nω-nitro-L-arginine (L-NNA) as an inhibitor of NO synthase, an enzyme that catalyses the production of nitric oxide (NO) from L-arginine. Methods: This study investigated the differential effects of L-arginine and L-NNA on markers of oxidative stress and biochemical changes in brain tissue from rats with different levels of resistance to hypoxia exposed to lead nitrate. Rats with either low or high resistance to hypoxia were exposed to lead nitrate (oral 3.6 mg lead nitrate/kg b.w. per day for 30 days) and treated with L-arginine (600 mg/kg b.w., i.p., 30 min before and after exposure to lead nitrate) or L-NNA (35 mg/kg b.w., i.p., 30 min before and after exposure to lead nitrate). Brain tissue samples were analysed for lipid peroxidation, oxidative modification of proteins, and activity of antioxidant enzymes, including superoxide dismutase, catalase, glutathione reductase, and peroxidase, and total antioxidant status (TAS). We also examined the biomarkers of biochemical pathways involving the activity of alanine and aspartate aminotransferases, succinate dehydrogenase (SDH), and α-ketoglutarate dehydrogenase (KGDH). In addition, the trend observed was supported by assessments of the acetylcholine levels and acetylcholinesterase activity (ACh-AChE system) in brain tissue. Results: In rats with low resistance to hypoxia, the L-arginine treatment significantly reduced lipid peroxidation and oxidative protein modification but increased antioxidant enzyme activity, suggesting a protective effect against lead-induced oxidative stress. Conversely, in rats with high resistance to hypoxia, L-NNA had a protective effect, reducing lead-induced oxidative damage and decreasing lipid peroxidation, whereas L-arginine exacerbated oxidative stress and impaired antioxidant defences. These findings were supported by corresponding changes in the acetylcholine-acetylcholinesterase system, reflecting the observed patterns of lead-induced oxidative stress and neurotoxicity. The study shows that L-arginine exerts a protective effect by reducing lead-induced oxidative damage via an improvement in TAS. Our study shows that lead nitrate exposure significantly increases ala-nine and aspartate aminotransferase activity in brain tissue, with L-arginine exacerbating and L-NNA reversing this effect. The lead nitrate exposure also affected the activities of SDH and KGDH, which are important for cellular energy production and hypoxia resistance, with L-arginine altering SDH activity depending on the level of resistance and L-NNA enhancing both SDH and KGDH activities. These trends were further validated by alterations in the ACh-AChE system, highlighting the differential role of NO-dependent mechanisms in modulating lead-induced neurotoxicity based on hypoxia resistance. Conclusion: These findings suggest potential targeted therapeutic strategies based on the oxidative stress profile and highlight the potential of nitric oxide system modulators in counteracting lead-induced biochemical alterations and the dynamics of the ACh-AChE system depending on the individual physiological reactivity of organisms.

Effects of continuous and transgenerational rearing in peanut leaves on the performance and enzyme activity of Spodoptera frugiperda (Lepidoptera: Noctuidae).

The invasive fall armyworm (FAW), Spodoptera frugiperda, is a polyphagous pest that significantly threatens crops worldwide. FAW may undergo adaptation, enhancing its ability to infect specific plant hosts. However, there is limited knowledge on this topic. After 8 generations of constant rearing on peanut leaves, the performance and enzyme activities of FAW were investigated in this study. Compared to FAW fed on the peanut cultivars 'Fuhua 8' and 'Quanhonghua 1' for 2 generations, those grown on leaves for 5 to 8 generations had significantly shorter pre-adult development times and total preoviposition periods. Fecundity also increased significantly, resulting in an overall improvement in population fitness as measured by demographic parameters. However, the F2 generation of FAW fed on corn leaves outperformed the F8 generation of FAW fed on peanut leaves. In the F2 generation, the FAW peanut population exhibited 30-55% supernumerary larval molts, which decreased substantially in the F5 and F8 generations. Notably, supernumerary larval molts displayed pupation and emergence rates comparable to normal larvae, regardless of the peanut cultivar or rearing generation. The activities of lipase and acetylcholinesterase increased significantly from the F2 to F8 generations, showing substantial negative and positive correlations with larval development time and fecundity, respectively. In conclusion, FAW demonstrated inferior performance on peanut leaves compared to corn leaves, despite its performance was significantly improved after 5 to 8 generations of acclimation. These results suggest that corn will continue to be the primary target crop for FAW in China.

Behaviour, biochemical and histological responses of the freshwater mussels Unio ravoisieri exposed to wastewater from Wadi Guenniche (Northeastern Tunisia)

ABSTRACT Wastewater effluents increase contaminant levels in the aquatic environment, leading to various disruptive effects. In this study, responses of Unio ravoisieri transplanted into wastewater from Wadi Guenniche were monitored using filtration rate, oxidative stress, lipo-peroxidation, neurotoxicity and histopathological markers. The filtration rate was significantly increased by exposure to diluted wastewater, rising from 35.13 mg indiv−1 h−1 in the control to 63.49 mg indiv−1 h−1 in the mussels after 96 h of exposure. In contrast, this exposure significantly reduces catalase, glutathione-S-transferase and acetylcholinesterase activities in both organs. This decrease is dependent on the effluent concentration and time exposure. The malondihaldehyde content showed an increasing profile in both organs. It is only in the gills that this increase is significant for mussels transplanted in situ for 48 h. Contamination by wastewater causes histopathological changes in both organs, marked by infiltration, vacuolisation, secretion of lipofuscins and cell necrosis. The intensity of these lesions depends on the duration of exposure and the degree of pollution. The mean incidence of lesions increases depending on effluent concentration and exposure time in both organs. Our study contributes to the database on behavioural, biochemical and histopathological effects in mussels following the discharge of wastewater effluent into a freshwater ecosystem.

Synthesis of newly designed hydrazones, in vitro and in silico studies, and structure-activity relationship

Herein, new N'-(substituted benzylidene)-3,5-dihydroxybenzohydrazide (1–13) series were synthesized, and their antioxidant, anticholinesterase, anti-tyrosinase, anti-urease, and antidiabetic activities were investigated together with in silico studies. The synthesized derivates were characterized using molecular spectroscopy, and the structure-activity relationships (SAR) were discussed for all tested biological assays. According to activity results, compound 3 exhibited excellent antioxidant activity in all tests, while compound 1 demonstrated the best acetylcholinesterase (AChE) inhibitory and butyrylcholinesterase (BChE) inhibitory activities. On the other hand, compound 11 showed excellent tyrosinase inhibitory (IC50:3.02±0.10 mM) and urease inhibitory (IC50:9.21±0.27 µM) activity. Moreover, among the synthesized compounds, compound 6 was detected as the best antidiabetic compound by inhibiting α-amylase (IC50:30.68±0.94 µM) and α-glycosidase (IC50:41.35±0.03 µM) enzymes, which were related with the antidiabetic activity. Molecular docking analysis confirmed AChE, BChE, tyrosinase, urease, α-amylase, and α-glucosidase inhibitory activities. In line with the findings obtained from in vitro bioactivity results and molecular docking analysis, hydrazone compounds are a suitable class of organic compounds for developing acetylcholinesterase, butyrylcholinesterase, urease, α-amylase, and α-glucosidase inhibitors.

Natural Products and Their Neuroprotective Effects in Degenerative Brain Diseases: A Comprehensive Review.

As the global population ages, the incidence of neurodegenerative diseases such as Alzheimer's and Parkinson's is rapidly rising. These diseases present a significant public health challenge, as they severely impair cognitive and motor functions, ultimately leading to a substantial reduction in quality of life and placing a heavy burden on healthcare systems worldwide. Although several therapeutic agents have been developed to manage the symptoms of these diseases, their effectiveness is often limited, and there remains an urgent need for preventive strategies. Growing evidence indicates that bioactive compounds from natural products possess neuroprotective properties through antioxidant and anti-inflammatory effects, modulating key pathways such as phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and brain-derived neurotrophic factor-tropomyosin receptor kinase B-cAMP response element-binding protein (BDNF-TrkB-CREB), which are crucial for neuronal survival. These compounds may also reduce amyloid-beta and tau pathology, as well as enhance cholinergic neurotransmission by inhibiting acetylcholinesterase activity. By targeting oxidative stress, neuroinflammation, and neurodegeneration, natural products offer a promising approach for both prevention and treatment. These findings suggest that natural products may be promising for preventing and treating neurodegenerative diseases. This review aims to explore the pathogenesis of neurodegenerative diseases, the limitations of current therapies, and the potential role of natural products as therapeutic agents.

Evaluation of the effects of two commercial pesticides on Daphnia magna in different feeding environments using morphological and biochemical markers

ABSTRACT In this study, the impact of exposure to a glyphosate-based herbicide (GBH) and a trifloxystrobin-based fungicide (TBF) on Daphnia magna in diverse feeding environments was assessed through the analysis of morphological and biochemical markers. The test organisms selected for analysis were Chlorella vulgaris and D. magna. First, the 48-hour median lethal concentrations (LC50) of GBH and TBF for D. magna were determined to be 253.1 mg/L and 20.7 µg/L, respectively. Secondly, the lethality, length, width, and spin length of D. magna were evaluated following exposure to sublethal pesticide concentrations, selected based on the LC50 values, in different feeding environments. Thirdly, the activities of glutathione S-transferase (GST), glutathione reductase, catalase (CAT), carboxylesterase, and acetylcholinesterase, as well as the levels of reduced glutathione, were measured in D. magna exposed to sublethal pesticide concentrations in different feeding environments. Both pesticides caused an increase in CAT activity, while GBH also caused an increase in GST activity in the unfed and mixed-fed groups. Conversely, it can be concluded that feeding with C. vulgaris reduces oxidative stress and toxic effects since there was a lesser increase in GST and CAT activities in the C. vulgaris-fed group for both pesticides, similar to the lethality.

Scoliidines: Neuroprotective Peptides in Solitary Scoliid Wasp Venoms.

A comprehensive LC-MS study examined the venom components of the solitary scoliid wasp Scolia oculata. Online mass fingerprinting showed that crude venom contains 25 small molecules (amino acids, biogenic amines, and nucleosides/nucleotides) and 45 peptides with MW 400-2700. The small molecules were identified by elemental composition analysis, and peptide sequences were determined by ESI-MS/MS and MALDI-TOF/TOF MS analyses. As major peptide components, a known peptide, β-scoliidine (DYVTVKGFSPLRKA), and three new peptides, γ-scoliidine (YVTVKGFSPLR), δ-scoliidine (YVTVKGFSPLREP) and ε-scoliidine (DYVTVKGFSPLREP) were identified, all of which are closely homologous to each other. Once the neuroprotective effects of β-scoliidine have already been described, the other three new scoliidine peptides were analyzed against oxidative stress-induced toxicity in PC12 neuronal cells by mitochondrial metabolism assay, and the structure-activity relationship was evaluated. Interestingly, pre-treatment with ε-scoliidine increased the mitochondrial metabolism of PC12 cells (106 ± 3.6%; p = 0.007) exposed to H2O2-induced oxidative stress in contrast to γ- and δ-scoliidines (77.6 ± 4.8 and 68.5 ± 4.1%, respectively) in compared to cells treated only H2O2 (75.8 ± 2.4%). These new peptides were also analyzed for enzyme inhibitor/substrate assays with angiotensin-converting enzyme (ACE), neprilysin (NEP), and acetylcholinesterase (AChE). In these assays, only δ- and ε-scoliidines increased the AChE activity (128.7 ± 3.8%; p = 0.01; and 116.8 ± 3.8% p = 0.03; respectively) in relation to basal activity (100.1 ± 1.6%). In addition, the four peptides were analyzed through in silico analysis, and none of them demonstrated possible hemolytic and toxic activities. In our study, the comprehensive LC-MS and MS/MS analyses of Scolia oculate venom identified four major peptide components of the venom β-, γ-, δ- and ε-scoliidines, and small differences in their primary structures are important to their neuroprotective properties.

Evaluating Antioxidant Enzyme Parameters in Rats Treated with Berberine-Loaded Bovine Serum Albumin Nanoparticles and Scopolamine

Abstract Introduction/Objective Introduction: Berberine (BER) has garnered attention for its antioxidant properties demonstrated in various studies, showing its ability to scavenge or inhibit reactive oxygen species (ROS) and reactive nitrogen species (RNS), including nitric oxide, superoxide anion, and peroxynitrites. Methods/Case Report Methods: Forty-two male Wistar rats were randomly assigned to seven groups, each comprising 6 rats: Sham control (no treatment), BSA-NPs orally administered, BRB-NPs orally administered, SCO intraperitoneally injected, BER followed by SCO injection, BSA-NPs with SCO injection, and BER-NPs with SCO injection. Treatments were administered daily for 28 days. The cholinergic status was evaluated by assessing acetylcholinesterase (AChE) activity in brain homogenates, and brain homogenate Aβ-42 levels were measured using the ELISA technique. Additionally, brain prooxidant markers (NO, TBARS, XO), nonenzymatic antioxidants (GSH), and enzymatic antioxidants (GPx, GST, and SOD) were measured. Results (if a Case Study enter NA) Results: The study revealed that treatment with BRB NPs resulted in the lowest AChE activity and Aβ-42 levels. Scopolamine administration significantly increased brain NO, TBARS, and XO activity, accompanied by a progressive depletion in GSH content (p&amp;lt;0.05). Treatment with BRB-free or BSA decreased NO levels, while the BSA or BRB-NPs groups exhibited higher brain TBARS levels than the sham group. All treated groups exhibited similar activity to the sham control, except for the BSA-treated group. Furthermore, all treated groups showed comparable GSH levels to the sham control, except for the scopolamine group. Treatment with BRB NPs normalized GPx activity and showed the highest GST activity. The BRB-NPs treated group also exhibited the highest SOD level. The p-value was &amp;lt;0.001 among all studied groups. Conclusion Conclusion: Injection of SCO induced oxidative impairments in brain tissue, evidenced by increased prooxidants such as NO and depletion of antioxidant capacity (GPx, GST, and GSH). SCO also disrupted glutathione metabolism, enhancing the level of lipid peroxidation in the brain. Treatment with BRB-NPs or free BRB progressively increased antioxidant capacity and mitigated the harmful effects of oxidative damage in the brain by reducing prooxidant levels.

Response of oxidative stress and neurotoxicity biomarkers in rainbow trout (Oncorhynchus mykiss) after exposure to six-metal mixtures

ABSTRACT The activity of liver catalase and brain acetylcholinesterase was assessed in rainbow trout (Oncorhynchus mykiss) after 7- and 14-day exposure to a six-metal mixture at the maximum permissible concentrations accepted for inland waters in the EU (2013/39/EU; 2008/105/EC) (Zn − 0.1, Ni − 0.034, Cu − 0.01, Cr − 0.01, Cd − 0.0015 and Pb − 0.014 mg L−1) and to the same six-metal mixtures with tenfold reduced concentration of Cu and Cr ions. A statistically significant increase of up to 26% of catalase and 52% of acetylcholinesterase activity was observed in rainbow trout after 7 days of exposure to the six-metal mixture at the maximum permissible concentrations in comparison to a control group. After 14-day treatment, neither CAT nor AChE showed significant response to all tested metal mixtures. The six-metal mixture with the tenfold reduced concentration of Cr increased brain AChE activity in O. mykiss after 7 days of exposure (35%). Enhancement of catalase activity caused by the mixture of the six metals at the maximum permissible concentrations and the increased acetylcholinesterase activity in response to the same metal mixture and mixture with tenfold reduced Cr concentration after 7 days of exposure indicates the induction of oxidative stress and disturbance of cholinergic system homeostasis respectively.