Decrease In AChE Activity Research Articles

L-Arginine and Intermittent Hypoxia Are Stress-Limiting Factors in Male Wistar Rat Models.

The aim of this study was to evaluate the combined effects of L-arginine, intermittent hypoxia training (IHT), and acute stress on oxygen-dependent processes in rats, including mitochondrial oxidative phosphorylation, microsomal oxidation, and the intensity of lipoperoxidation processes. In addition, our study investigated how the modulatory effect of the NO synthase mechanism on the concentration of catecholamines (CA), such as adrenaline and noradrenaline, and their biosynthetic precursors (DOPA, dopamine) varies depending on the cholinergic (acetylcholine, Ach-acetylcholinesterase, AChE) status in rats. This study investigated the protective stress-limiting effects of L-arginine impact and IHT in the blood and liver of rats. The results showed that L-arginine promoted the maintenance of NAD-dependent oxidation in mitochondria, which was detrimental compared to succinate oxidation, and was accompanied by depletion of respiratory activity reserves under stress induced by high concentrations of CA. The interdependence of SC-dependent oxidation and the functional role of NAD-dependent substrate oxidation in the mitochondrial respiratory chain in stress conditions induced using inhibitors revealed the importance of the NO system. Administration of L-arginine during the IHT course prior to stress exposure increased the compensatory capacity of the organism. L-arginine increased the compensatory capacity of the sympathoadrenal system in stress-exposed rats. In the early stages of IHT, modulation of the CA concentration was observed with a concomitant increase in lipoperoxidation processes, and in the final stages of IHT, the CA concentrations increased, but there was also an inhibition of lipoperoxidation, which was particularly enhanced by the administration of L-arginine. The increase in blood concentrations of CA and ACh was accompanied by a decrease in AChE activity at different stages of adaptation to hypoxia induced by IHT (days 5, 10, and 14). Thus, the IHT method significantly mobilises the reserve capacity of oxygen-dependent processes through the system of CA, ACh-AChE mediated by nitric oxide.

Genotoxic impact of agricultural insecticides as contaminants of river Teesta on the resident fish Pethia Conchonius.

Fish, being highly sensitive to changes in the physico-chemical parameters of water, are good indicators of contamination. Teesta, a prominent northern West Bengal River system, is increasingly contaminated due to anthropogenic activities. This study aims to determine agricultural pesticide contamination and its genotoxic impact on the resident fish, Pethia conchonius, as an experimental organism. Sample water analysis from three riverine sites I, II & III, showed the presence of the insecticides imidacloprid (IMI), chlorpyrifos (CPF), bifenethrin (BF), cypermethrin (CP), difenthiuron, acetamiprid (AC) in the sites II and III only with adjoining agricultural lands. Comet assay revealed a significantly lower % Head DNA (~ 1.2 times), higher %Tail DNA (~ 16 times), and %Tail length (~ 3.1 times) in the gills of Pethia conchonius from sites II and III. About 4 and 10 times increase of micronuclei and other nuclear abnormalities were also noted in the erythrocytes of the fish from sites II and III than I, which was not contaminated. The antioxidant enzymes SOD, CAT, and GST activity and MDA levels were significantly higher (p < 0.05) in the liver samples from sites II and III, while AChE activity was significantly decreased (p < 0.001) in the brain tissues. Moreover, the sod, cat, and gpx expression in the hepatic cells were significantly upregulated compared to the β actin mRNA indicating increased oxidative stress. Increased genomic damage, antioxidant enzyme activity, higher MDA levels, decreased AChE activity in the brain, and the upregulation of hepatic genes strongly suggested the genotoxic effects of the detected insecticides in combination with other contaminants.

Exposure to 2,4-Dichlorophenoxyacetic acid stimulates the calcium/ROS/CK1α pathway to trigger Hemolysis and Eryptosis in red blood cells.

The agricultural herbicide 2,4-dichlorophenoxyacetic (2,4-D) is cytotoxic to human red blood cells (RBCs) by virtue of oxidative hemolysis. Nevertheless, there remains a great paucity of literature detailing the mechanisms by which 2,4-D triggers hemolysis. Also, the eryptotic effects of 2,4-D has thus far been largely overlooked. This study aims to expand current understanding of the cytotoxic properties of 2,4-D in RBCs. Cells were exposed to 2,4-D ranging from 100 to 1,000μM for 24h at 37°C under varied experimental conditions. Hemolysis, LDH, AST, and AChE activities were photometrically measured. Flow cytometry assessed eryptotic markers including cell volume by forward scatter (FSC), phosphatidylserine (PS) externalization by annexin-V positivity, reactive oxygen species by H2DCFDA, and intracellular Ca2+ levels by Fluo4/AM. 2,4-D induced Ca2+-independent, concentration-responsive hemolysis paralleled by increased LDH, AST, and K+ in the supernatant, which was significantly blunted by D4476, isosmotic urea, sucrose, and polyethylene glycol 8,000 (PEG). Notably, 2,4-D caused a significant increase in cells positive for annexin-V-FITC, DCF, and Fluo4 with a concomitant decrease in AChE activity and FSC following KCl release. Furthermore, lymphocytes and reticulocytes were sensitive to 2,4-D within a whole blood milieu. This work introduces novel cytotoxic mechanisms of 2,4-D in RBCs and reveals its pro-eryptotic effects. 2,4-D toxicity is neutralized by blockade of casein kinase 1α signaling and the presence of urea, sucrose, and PEG. These findings have significant implications for public health and inform future health risk assessments to develop novel preventive and therapeutic strategies.

6-Shogaol Abrogates Parkinson’s Disease in Rotenone-Induced Rodents: Based on In Silico Study and Inhibiting TNF-α/NF-κB/IL-1β/MAO-B

Background/Objectives: 6-Shogaol is a comparatively innovative anti-Parkinson’s remedy with antioxidant and anti-inflammatory characteristics. This investigation intended to determine the role of 6-shogaol in the Parkinson’s disease (PD) paradigm in rotenone-induced rats. Methods: Thirty male Wistar rats (10–12 weeks old; 180 ± 20 g) were divided into five groups. Animals with rotenone-induced experimental PD were subsequently treated with 6-shogaol-10 at 20 mg/kg for 28 days. After the experimental duration, behavioural investigations were performed, i.e., open field test, forced swim test, rotarod test, and catalepsy test. Biochemical assessments like AChE, GSH, CAT, SOD, MDA, nitrite, ceruloplasmin, proinflammatory markers such as IL-1β, NF-κB, TNF-α, and catecholamines markers (DA, GABA, and MAO-B) were determined. The docking procedure was conducted using the AutoDock Vina docking protocol. Furthermore, histopathology was performed. Results: Rotenone significantly increased the level of MAO-B, oxidative, nitrative, and pro-inflammatory markers. However, there was a decline in ceruloplasmin, dopamine, and endogenous antioxidants. Treatment with 6-shogaol (10 and 20 mg/kg) considerably sustained the elevation of oxidative stress and inflammatory indicators and decreased AChE activity and dopamine levels. In the histology of the brain, 6-shogaol improved the neuronal structure and reduced the degeneration of neurons. Based on the binding energy values, compound 6-shogaol demonstrates a favourable binding affinity to AChE, MAO-B, DA, and GABA with respective binding energies of −8.214, −8.133, −7.396 and −6.189 kcal/mol. Conclusions: In this study, 6-shogaol exhibited neuroprotective properties against PD, which could be employed as a prospective medication for PD.

Sorption of PFOS onto polystyrene microplastics potentiates synergistic toxic effects during zebrafish embryogenesis and neurodevelopment

Microplastics (MPs) have become an emerging anthropogenic pollutant, and their ability to sorb contaminants potentially enhances the threats to the ecosystem. Only a few studies are available to understand the combined effects of microplastics and other pollutants. The present study investigated the sorption of perfluorooctane sulfonic acid (PFOS) onto polystyrene microplastics (PS-MPs) at varying concentrations, using molecular dynamics simulation (MDS) to preliminarily explore the adsorption behavior. The MDS results revealed negative interaction energies between PFOS and PS-MPs, underscoring PS-MPs' role as a potential adsorbent for PFOS in an aqueous solution. Thereafter, zebrafish embryos were employed to explore the toxic effects of combined exposure to PS-MPs and PFOS. Fluorescence and Scanning Electron Microscopy (SEM) suggested PS-MP accumulation individually and in combination with PFOS on the embryonic chorion membrane. As a result, the exposed group showed increased inner pore size of the chorionic membrane and accelerated heartbeat, indicating hypoxic conditions and hindered gaseous exchange. PS-MPs aggravated the toxicity of PFOS during larval development manifested by delayed hatching rate, increased mortality, and malformation rate. Additionally, increased ROS accumulation and altered antioxidant enzymatic status were observed in all the exposed groups suggesting perturbation of the redox state. Additionally, co-exposure of zebrafish larvae to PS-MPs and PFOS resulted in an abrupt behavioral response, which decreased AChE activity and altered neurotransmitter levels. Taken together, our results emphasize that PS-MPs can act as a potential vector for PFOS, exerting synergistic toxic effects in the aquatic environment, and hence their health risks cannot be ignored.

Toxic effects of fenvalerate in tadpoles of Fejervarya limnocharis: a multiparametric study.

Pyrethroids are among the most widely used insecticides. Fenvalerate (FEN), a synthetic pyrethroid, is frequently used in domestic and agricultural settings to control insects which ultimately find its way into the aquatic ecosystems. The larval stages of amphibians, which are experiencing a rapid population decline, are spent in aquatic habitats, thus making them vulnerable to FEN exposure. The potential toxic effects of pyrethoids in general and FEN in particular are not well understood. The present study was carried out to assess the toxicity of FEN in tadpoles of Fejervarya limnocharis. FEN at different concentrations (0, 4, 5, 6, 7, and 8mg/L) induced substantial lethal effects. The estimated LC50 values were 8.54, 6.73, 5.44, and 4.44mg/L at 24, 48, 72, and 96h respectively. Exposure to environmentally relevant sub-lethal concentrations delayed metamorphosis and reduced survivality. FEN was found to be genotoxic in erythrocyte micronucleus and comet assay. Further, sub-lethal concentrations of FEN adversely affected the antioxidant defense mechanism of the exposed individuals with parallel increase oxidative damage to membrane lipids. The swimming behavior in the form of startle response, swirl response, and total movements was decreased with a concomitant decrease in AChE activity. In addition, FEN exhibited significant cardiotoxicity by decreasing the cardiac rate of the exposed individuals. The present findings clearly indicate that FEN can cause significant toxicity to the tadpoles of F. limnocharis affecting their survival and fitness in the natural environment.

Neurotoxic and cardiotoxic effects of pyrogallol on catfish (Clarias gariepinus)

Pyrogallol, a botanical hydrolysable tannin, has diverse medical and industrial applications. Its impact on aquatic ecosystems and fish health has been previously studied, revealing histopathological, immunological, biochemical, and haematological alterations in African catfish (Clarias gariepinus). In this study, the neurotoxic potential of pyrogallol was assessed through a 15-day exposure of catfish to concentrations of 1, 5, or 10 mg/L. Enzyme activities such as acetylcholinesterase (AchE), monoamine oxidase (MAO), aldehyde oxidase (AO), and nitric oxide (NO) were measured in serum and brain, along with histopathological examinations in the brain and heart. Pyrogallol exposure led to decreased AchE activity in the brain and serum, increased serum MAO activity, elevated AO in both brain and serum, and suppressed NO levels. Morphological abnormalities and dose-dependent pathological alterations were observed in the brain and heart, including neuropile deformities, shrunken Purkinje cells, cardiomyocyte degeneration, and increased collagen fibers. This suggests that pyrogallol induces adverse effects in fish.

REVIEW ON THE SYNTHESIS OF ALPHA-LIPOIC ACID AND ITS THERAPEUTIC POTENTIAL IN EXPERIMENTAL MODEL OF DEMENTIA

LA or (±)-α-Lipoic acid (6,8-thioctic acid, 5-(1,2-dithiolan-3-yl)pentanoic acid) (LA) is a heterocyclic thia fattyacid consisting of pentanoic acid and a 1,2-dithiolan-3-yl group at the 5-position. LA is an amphiphilic pharmacophorewith excellent antioxidant, anti-inflammatory and neuroprotective effects attested by numerous studies for its potentialutility in both the treatment and diverse forms of prophylaxis of neurodegenerative disorders, especially Alzheimer’sdisease. This article aims to assess the differences in neuroprotective effect after short-term (11 days) and longterm(51 days) LA administration in an experimental rat model of scopolamine-induced dementia by correlatingbiochemical data on acetylcholinesterase activity with behavioural data. Behaviourally appraised changes in learningand memory appear to correlate with biochemical changes in AChE activity. The neuroprotective effect of LA, asascertained by its beneficial effects on learning and memory in a scopolamine animal model, appears to be associatedwith cholinergic mechanisms (a decrease in AChE activity), and to be larger after short-term administration ratherthan long-term administration. These results further underscore the candidacy of LA as a viable drug candidatesuitable for continued investigation and derivate synthesis endeavours.

Neuroprotective effects of Shenghui decoction via inhibition of the JNK/p38 MAPK signaling pathway in an AlCl3-induced zebrafish (Danio rerio) model of Alzheimer's disease

Ethnopharmacological relevanceAlzheimer's disease (AD) is a multi-factorial degenerative disease, and multi-targeted therapies targeting multiple pathogenic mechanisms should be explored. Shenghui decoction (SHD) is an ancient traditional Chinese medicine (TCM) formula used clinically to alleviate AD. However, the precise mechanism of action of SHD as a therapeutic agent for AD remains unclear. Aim of the studyThis study investigated the neuroprotective properties and potential mechanisms of action of SHD in mitigating AD-like symptoms induced by AlCl3 in a zebrafish model. Materials and methodsActive components of SHD were detected using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Zebrafish were exposed to AlCl3 (200 μg/L) for 30 days to establish an AD zebrafish model. AlCl3-exposed zebrafish were treated with SHD or donepezil. Behavioral tests were used to assess learning and memory, locomotor activity, and AD-related anxiety and aggression in AlCl3-exposed zebrafish. Nissl staining and transmission electron microscopy were used to evaluate histological alterations in brain neurons. The concentrations of pro-inflammatory cytokines (tumor necrosis factor-α, TNF-α; interleukin-1β, IL-1β) were quantified using Enzyme-linked immunosorbent assay (ELISA). Markers of oxidative stress and cholinergic activity (acetylcholinesterase, AChE) were detected using biochemical assays. Western blotting and immunofluorescence were used to detect the protein expression levels of Aβ, p-tau, PSD-95, synaptophysin, TLR4, phosphorylation of NF-κB p65, p38, and JNK. ResultsFifteen SHD compounds were identified by UPLC-MS/MS analysis. SHD improved AlCl3-induced dyskinesia, learning and memory impairment, anxiety-like behavior, and aggressive behavior in zebrafish. AlCl3-exposed zebrafish showed AD-like pathology, overexpression of Aβ, hyperphosphorylated tau protein, marked neuronal damage, decreased expression of synaptic proteins, synaptophysin, and PSD-95, and impairment of synaptic structural plasticity. These effects were reversed by the SHD treatment. We also observed that SHD ameliorated oxidative stress and decreased AChE activity and inflammatory cytokine levels. These effects are similar to those observed for donepezil. Meanwhile, SHD could decrease the protein expression of TLR4 and inhibit phosphorylation of NF-κB, JNK, and p38 MAPK. These results demonstrate that SHD has the potential to exert neuroprotective effects, which may be partly mediated via inhibition of the JNK/p38 MAPK signaling pathway. ConclusionsOur findings revealed the therapeutic mechanism of SHD in mitigating AD progression and suggested that SHD is a potent neuroprotectant that contributes to the future development of TCM modernization and broader clinical applications.

Evaluation of oxidative stress indicators as toxicity parameters after chronic exposure of Drosophila melanogaster to free curcumin and curcumin-loaded nanocapsules

We investigated a possible toxic effect induced by chronic exposure to free curcumin and curcumin-loaded nanocapsules in Drosophila melanogaster, enabling safe applications. Flies of both sexes were divided into groups: control group; free curcumin at concentrations of 10, 30, 100, 300, 900, and 3000 μM; curcumin-loaded nanocapsules at concentrations of 10, 30, 100, and 300 μM. Initially, the diet consumption test was evaluated in flies exposed to different concentrations. During the 10-day treatment, the flies were evaluated for percentage survival. After the treatment, behaviors (geotaxis negative and open field), acetylcholinesterase activity (AChE), and oxidative stress parameters (reactive species (RS) and thiobarbituric acid reactive substances (TBARS) levels, Glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) enzymes activity, erythroid-derived nuclear factor 2 (Nrf2) immunoreactivity, and cellular metabolic capacity, were assessed. No significant difference in diet consumption, indicating that the flies equally consumed the different concentrations of free curcumin and the curcumin-loaded nanocapsules. Was observed that free curcumin and curcumin-loaded nanocapsules increased survival, locomotor and exploratory performance, decreased AChE activity, RS and TBARS levels, increased GST, SOD and CAT activity, Nrf2 and viable cells compared to the control. The chronic treatment did not cause toxicity, suggesting that nanoencapsulation of curcumin could be explored.

Early clues and molecular mechanism involved in neurodegenerative diseases induced in immature mice by combined exposure to polypropylene microplastics and DEHP

Studies have shown that exposure to either microplastics (MPs) or di-(2-ethylhexyl) phthalic acid (DEHP) alone can cause neurotoxicity in animals, but it remains uncertain whether and to what extent co-exposure to these two substances, which often occur together in reality, can also induce neurotoxicity. This study aimed to investigate the neurotoxicity and molecular mechanisms of combined exposure to DEHP and polypropylene microplastics (synthetic PP-MPs were used), the microplastics most commonly encountered by young children, in immature mice. The results showed that exposure to PP-MPs and/or DEHP did cause neurotoxic effects in immature mice, including induction of neurocognitive and memory deficits, damage to the CA3 region of the hippocampus, increased oxidative stress, and decreased AChE activity in the brain. The severity of the neurotoxicity increased with increasing concentrations of PP-MPs, combined exposure to PP-MPs and DEHP exhibited additive or synergistic effects. Transcriptomic analyses revealed that the PP-MPs and/or DEHP exposure altered the expression profiles of gene clusters involved in the stress response, and in protein processing in endoplasmic reticulum. Quantitative analyses further indicated that PP-MPs and/or DEHP exposure inhibited the activity of the heat shock response mediated by heat shock transcription factor 1, while chronically activated the unfolded protein response, consequently inducing neurotoxicity through neuronal apoptosis and neuroinflammation in the immature mice. As a pioneer study to highlight the neurotoxicity induced by combined exposure to PP-MPs and DEHP in immature mice, this research provides new insights into mitigating the health risks of PP-MPs and DEHP exposure in young children.

Sub-chronic exposure of Oreochromis niloticus to environmentally relevant concentrations of smaller microplastics: Accumulation and toxico-physiological responses

This study assesses the accumulation and toxic effects of environmentally relevant concentrations (0.01, 0.1 and 1 mg/L) of polystyrene MPs (1 µm) in Oreochromis niloticus (Nile tilapia) for 14 days. The results showed that 1 µm PS-MPs accumulated in the intestine, gills, liver, spleen, muscle, gonad and brain. RBC, Hb and HCT showed a significant decline, while WBC and PLT showed a significant increase after the exposure. Glucose, total protein, A/G ratio, SGOT, SGPT and ALP showed significant increments in 0.1 and 1 mg/L of PS-MPs treated groups. The increase in cortisol level and upregulation of HSP70 gene expression in response to MPs exposure indicate MPs-mediated stress in tilapia. MPs-induced oxidative stress is evident from reduced SOD activity, increased MDA levels and upregulated P53 gene expression. The immune response was enhanced by inducing respiratory burst activity, MPO activity and serum TNF-α and IgM levels. MPs exposure also led to down-regulation of CYP1A gene and decreased AChE activity, GNRH and vitellogenin levels, indicating the toxicity of MPs on the cellular detoxification mechanism, nervous and reproductive systems. The present study highlights the tissue accumulation of PS-MP and its effects on hematological, biochemical, immunological and physiological responses in tilapia with low environmentally relevant concentrations.

Biological Evaluation of Valeriana Extracts from Argentina with Potent Cholinesterase Inhibition for the Treatment of Neurodegenerative Disorders and Their Comorbidities—The Case of Valeriana carnosa Sm. (Caprifoliaceae) Studied in Mice

Alzheimer's disease (AD) is a neurodegenerative disorder whose pathophysiology includes the abnormal accumulation of proteins (e.g., β-amyloid), oxidative stress, and alterations in neurotransmitter levels, mainly acetylcholine. Here we present a comparative study of the effect of extracts obtained from endemic Argentinian species of valerians, namely V. carnosa Sm., V. clarionifolia Phil. and V. macrorhiza Poepp. ex DC from Patagonia and V. ferax (Griseb.) Höck and V. effusa Griseb., on different AD-related biological targets. Of these anxiolytic, sedative and sleep-inducing valerians, V. carnosa proved the most promising and was assayed in vivo. All valerians inhibited acetylcholinesterase (IC50 between 1.08-12.69 mg/mL) and butyrylcholinesterase (IC50 between 0.0019-1.46 mg/mL). They also inhibited the aggregation of β-amyloid peptide, were able to chelate Fe2+ ions, and exhibited a direct relationship between antioxidant capacity and phenolic content. Moreover, V. carnosa was able to inhibit human monoamine oxidase A (IC50: 0.286 mg/mL (0.213-0.384)). A daily intake of aqueous V. carnosa extract by male Swiss mice (50 and 150 mg/kg/day) resulted in anxiolytic and antidepressant-like behavior and improved spatial memory. In addition, decreased AChE activity and oxidative stress markers were observed in treated mouse brains. Our studies contribute to the development of indigenous herbal medicines as therapeutic agents for AD.

EVALUATION OF THE NEUROPROTECTIVE EFFECTS OF HYDROETHANOLIC EXTRACT OF DIOSPYROS MESPILLIFORMIS TRUNK BARK (EBENACEA) ON DIAZEPAM-INDUCED AMNESIA IN MICE

Diospyros mespilliformis (DM) is a plant of the Ebonaceae family that is commonly used in traditional medicine to treat epilepsy and schizophrenia. Radial arm mazes (RAM), Y mazes, and the novel object recognition test (NOR) were used to assess working and reference memory in mice. After the different tests, the hippocampus of the animals was separated for the determination of biochemical markers such as acetylcholinesterase (AchE), malondialdehyde (MDA), and superoxide dismutase (SOD). The plant extract produced a significant rise in the percentage of alternation of mice in the Y-maze test, the time to observe the new object at the dose of 50 mg/kg (p&lt;0.01), and the discrimination index (p&lt;0.001) in all animals treated with the extract compared to the negative control. The result of the RAM test showed a significant decrease (p&lt;0.05) in the number of errors on the reference memory in animals treated with the extract at 100 mg/kg. The extract significantly decreased AchE activity, and MDA concentration, and significantly increased SOD activity compared to the negative control group. These effects of the hydroethanolic extract on working memory and reference DM extract would be related to the phenolic compounds quantified in the plant extract.

Neuroprotective effects of total alkaloids fraction of Huperzia serrata on scopolamine-induced neurodegenerative animals.

Huperzia serrata contains Huperzine A (HupA)-an alkaloid used to treat cognitive dysfunction. In this study, we used the total alkaloids (HsAE) to investigate their potential in managing cognitive impairment in comparison with HupA. The antioxidant activity was measured by DPPH assay. In the cellular study, the cell viability and level of ACh of SH-SY5Y cells were evaluated after pretreated with HsAE and scopolamine. For in vivo assay, mice were pre-treated with HsAE, and HupA and undergone scopolamine injection for cognitive impairment. The behavioral tests including the Y-maze and Morris water maze test and the AChE activity, the SOD, CAT, MDA level in the hippocampus and cortex were evaluated. HsAE showed significant scavenging properties on DPPH radicals. HsAE was not toxic to SH-SY5Y cells, and can rescue these cells upon scopolamine treatment. Intriguingly, HsAE showed the neuroprotection against scopolamine-induced amnesia in mice. Moreover, HsAE decreased AChE activity, MDA level, increased antioxidative enzyme activity in the hippocampus as well as cortex of mice, which was relatively better than that of HupA. These findings suggested that HsAE may significantly protect the neurons of mice with scopolamine-induced memory impairment connected to AChE depletion and oxidative stress.

Protective effects of dietary supplementation of probiotic Bacillus licheniformis Dahb1 against ammonia induced immunotoxicity and oxidative stress in Oreochromis mossambicus

The goal of this study was to assess the efficacy of probiotics in mitigating ammonia-induced toxicity in fish. Fish were divided into four groups: control, only probiotic, only ammonia, and combined ammonia + probiotic. For 8 weeks, the Oreochromis mossambicus were exposed to waterborne ammonia at 1.0 mg L−1 and/or dietary Bacillus licheniformis Dahb1 at 107 cfu g−1. After the 4th and 8th weeks, the fish were evaluated for growth performance, enzymatic and non-enzymatic antioxidant activities (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) reduced glutathione (GSH), neurotoxicity (acetylcholinesterase – AChE), non-specific immune responses (lysozyme (LYZ), myeloperoxidase (MPO), reactive nitrogen and oxygen species (RNS and ROS) and oxidative stress effects (lipid peroxidation (LPO), DNA damage)). Our results showed that in the absence of waterborne ammonia exposure, B. licheniformis Dahb1 significantly improved growth performance, enzymatic and non-enzymatic antioxidant capacity, AChE activity, non-specific immune response and decreased oxidative stress effect. Ammonia exposure resulted in significantly lower growth performance, reduced enzymatic and non-enzymatic antioxidant ability, decreased AChE activity, decreased non-specific immune response and increased oxidative stress effect. When O. mossambicus were exposed to ammonia, supplementation with B. licheniformis Dahb1 in the diet significantly increased survival, indicating that it may have a significant protective effect against ammonia toxicity by enhancing enzymatic and non-enzymatic antioxidant ability, activity of AChE, non-specific immune response and reduced oxidative stress effect. According to our findings, diet supplementation of B. licheniformis Dahb1 (107 cfu g−1) has the potential to combat ammonia toxicity in O. mossambicus.

Chinese Herbal Extracts Exert Neuroprotective Effect in Alzheimer's Disease Mouse Through the Dopaminergic Synapse/Apoptosis Signaling Pathway.

Background: Alzheimer’s disease (AD) as an age-related, irreversible neurodegenerative disease, characterized by cognitive dysfunction, has become progressively serious with a global rise in life expectancy. As the failure of drug elaboration, considerable research effort has been devoted to developing therapeutic strategies for treating AD. TCM is gaining attention as a potential treatment for AD. Gastrodia elata Blume, Polygala tenuifolia Willd., Cistanche deserticola Ma, Rehmannia lutinosa (Gaertn.)DC., Acorus gramineus Aiton, and Curcuma longa L. (GPCRAC) are all well-known Chinese herbs with neuroprotective benefits and are widely used in traditional Chinese decoction for AD therapy. However, the efficacy and further mechanisms of GPCRAC extracts in AD experimental models are still unclear. The purpose of this study was to investigate the synergistic protective efficacy of GPCRAC extracts (composed of extracts from these six Chinese medicines), and the protein targets mediated by GPCRAC extracts in treating AD. Methods: Scopolamine-induced cognitive impairment mouse model was established to determine the neuroprotective effects of GPCRAC extracts in vivo, as shown by behavioral tests and cerebral cholinergic function assays. To identify the potential molecular mechanism of GPCRAC extracts against AD, label-free quantitative proteomics coupled with tandem mass spectrometry (LC-MS/MS) were performed. The integrated bioinformatics analysis was applied to screen the core differentially expressed proteins in vital canonical pathways. Critical altered proteins were validated by qPCR and Western blotting. Results: Administration of GPCRAC extracts significantly recovered scopolamine-induced cognitive impairment, as evidenced by the improved learning and memory ability, increased Ach content and ChAT activity, as well as decreased AchE activity in the hippocampus of mice. In total, 390 proteins with fold-change>1.2 or <0.83 and p < 0.05 were identified as significant differentially expressed proteins, of which 110 were significantly up-regulated and 25 were significantly down-regulated between control and model group. By mapping the significantly regulated proteins, we identified five hub proteins: PPP2CA, Gsk3β, PP3CC, PRKACA, and BCL-2 that were associated with dopaminergic synapse and apoptosis signaling pathway, respectively. Western blotting and QPCR demonstrate that the expression levels of these core proteins could be significantly improved by the administration of GPCRAC extracts. These pathways and some of the identified proteins are implicated in AD pathogenesis. Conclusion: Administration of GPCRAC extracts was effective on alleviating scopolamine-induced cognitive impairment, which might be through modulation of dopaminergic synapse and apoptosis signaling pathway. Consequently, our quantitative proteome data obtained from scopolamine-treated model mice successfully characterized AD-related biological alterations and proposed novel protein biomarkers for AD.

The Effect of α-Tocopherol on the Reduction of Inflammatory Processes and the Negative Effect of Acrylamide.

Our research aimed to show acrylamide’s influence on inflammatory processes, the oxidative stress it causes in the cholinergic system, and the possibility of reducing inflammation via supplementation with α-tocopherol. For this purpose, an in ovo model was used where the embryos were exposed to acrylamide, α-tocopherol and a cocktail of these substances. After 48 h of exposure, we collected brain samples and performed biochemical assays to examine the effect of the chosen substances on oxidative stress (malondialdehyde-MDA and reduced glutathione-GSH) and acetylcholinesterase activity (AChE). The results showed that acrylamide decreased AChE activity in the examined brain samples by about 25% in comparison to the control group, and this effect was decreased by administering α-tocopherol. The concentration of malondialdehyde significantly increased in the group given acrylamide, while, in the group with α-tocopherol, the observed concentration was lower in comparison to the control group. Moreover, a decrease in glutathione concentration was observed after the administration of acrylamide; however, the protective effect of α-tocopherol was only slightly visible in this case. In conclusion, α-tocopherol minimizes the harmful effects of acrylamide on AchE, and it can minimize the concentration of MDA.

Ameliorative activity of medicinal plant fraction for neuroprotection against acrylamide-induced neurotoxicity in Drosophila melanogaster\u2014a comparative study

BackgroundMedicinal plant extracts used in folk medicine seem to be crucial since those are generally accepted by people without worrying about the toxicity. In our present study, we have compared the neuroprotective role of the rhizome of Curculigo orchioides Gaertn. and leaf extracts of Olea dioica Roxb., against acrylamide-induced neurotoxicity in Drosophila melanogaster.ResultsIn-vivo neurotoxic study was carried out using 7-day-old flies (wild-type D. melanogaster). Prior to co-after exposing the flies with acrylamide (8 mM) along with or without OLE-2 and CU-3 fractions (0.2, 0.4 and 0.6% w/v), the heads of flies of both the control and treated groups were homogenized for biochemical assay. ACR-treated groups have shown higher elevation in AChE, SOD, LPO, and CAT activity when compared to control and treated (plant fraction) groups. Biochemical and histopathology studies show that both the plant fractions (OLE-2 and CU-3) have neuroprotective action against acrylamide.ConclusionThe present study has demonstrated that dietary supplementation with plant fraction of OLE-2 and CU-3 has increased antioxidant enzymes and decreased AChE activity in D. melanogaster. This activity could be part of the probable mechanisms of action by which OLE-2 and CU-3 fractions have extended the lifespan and locomotory activity in fruit flies. These fruit flies continue to provide an exciting system for metabolic studies and should be more extensively exploited. Based on these results, further studies on the identified bioactive compounds from these two plants are being planned.

Neuroprotective potential of Malva neglecta is mediated via down-regulation of cholinesterase and modulation of oxidative stress markers.

Alzheimer's disease affects daily routine due to loss of memory and decline in cognition. In vitro data showed acetylcholine esterase inhibition activity of Malva neglecta but no in vivo evidence is available. The current study aims to investigate the anti-Alzheimer's activity of Malva neglecta methanolic extract in the AlCl3-induced Alzheimer disease rats' model. Thirty Wistar rats were divided into six groups and respective doses were given orally for 21days. Behavioural observations were recorded and biochemical analysis was performed on brain homogenate. Improvement in memory and cognition was noted in treated rats as compared to disease control. A dose-dependent decrease (0.530 ± 0.009 at 200mg/kg, 0.212 ± 0.007 at 400mg/kg, 0.173 ± 0.005 at 600mg/kg) in AChE activity was noted in the treatment groups with reference to disease control value (1.572 ± 0.013). This decrease in AChE activity is linked with an increase in acetylcholine in the brain which plays a key role in retaining memory. Oxidative stress biomarkers; GSH (66.77 ± 0.01 at 600mg/kg), SOD (26.60 ± 0.10 at 600mg/kg), CAT (21.46 ± 0.01 at 600mg/kg) levels were increased with a decrease in MDA (103.33 ±0.49 at 600mg/kg) level in a dose-dependently manner in the treatment groups as compared to disease control respective values. It is concluded that Malva neglecta could ameliorate Alzheimer's symptoms possibly by decreasing AChE activity and oxidative stress.