Reduced Acetylcholinesterase Activity Research Articles

Enhancement of debitterness, water-solubility, and neuroprotective effects of naringin by transglucosylation.

Naringin found in citrus fruits is a flavanone glycoside with numerous biological activities. However, the bitterness, low water-solubility, and low bioavailability of naringin are the main issues limiting its use in the pharmaceutical and nutraceutical industries. Herein, a glucansucrase from isolated Leuconostoc citreum NY87 was used for trans-α-glucosylattion of naringin by using sucrose as substrate. Two naringin glucosides (O-α-D-glucosyl-(1'''' → 6″) naringin (compound 1) and 4'-O-α-D-glucosyl naringin (compound 2)) were purified and determined their structures by nuclear magnetic resonance. The optimization condition for the synthesis of compound 1 was obtained at 10mM naringin, 200mM sucrose, and 337.5mU/mL at 28°C for 24h by response surface methodology method. Compound 1 and compound 2 showed 1896- and 3272 times higher water solubility than naringin. Furthermore, the bitterness via the human bitter taste receptor TAS2R39 displayed that compound 1 was reduced 2.9 times bitterness compared with naringin, while compound 2 did not express bitterness at 1mM. Both compounds expressed higher neuroprotective effects than naringin on human neuroblastoma SH-SY5Y cells treated with 5mM scopolamine based on cell viability and cortisol content. Compound 1 reduced acetylcholinesterase activity more than naringin and compound 2. These results indicate that naringin glucosides could be utilized as functional material in the nutraceutical and pharmaceutical industries. KEY POINTS: • A novel O-α-D-glucosyl-(1 → 6) naringin was synthesized using glucansucrase from L. citreum NY87. • Naringin glucosides improved water-solubility and neuroprotective effects on SH-SY5Y cells. • Naringin glucosides showed a decrease in bitterness on bitter taste receptor 39.

Polystyrene microplastics modulated bdnf expression triggering neurotoxicity via apoptotic pathway in zebrafish embryos

A ubiquitous presence of microplastics and nanoplastics created a new toxicological research area arising concept of “plastic rivers”. But, the precise molecular mechanisms by which its exposure affects developmental neurotoxicity are poorly understood. Hence, in the present investigation, healthy zebrafish embryos were exposed to different concentrations of 500 nm polystyrene microplastics (0.1 ppm, 1 ppm and 10 ppm) to assess the neurotoxicity and the underlying biomolecular mechanism. On the last day of exposure, behaviour, accumulation, embryotoxicity, acridine orange staining, antioxidant enzyme assay, acetylcholinesterase assay, nitric oxide (NO) estimation, along with neurotransmitter (serotonin, dopamine) quantification and gene expression using qRT-PCR (bdnf, p53, bcl-2, caspase-3, caspase-9) were performed. As a result, we found that zebrafish embryos ingest and bioaccumulate microplastic without causing any morphological changes and lethality. The survival and hatching rates of the embryos were also unaffected but the swimming behaviour patterns were found to be altered. Further, acridine orange staining exhibited more apoptosis in treated groups with increased p53, caspase-3, caspase-9 and decreased bcl-2 gene expression. Moreover, polystyrene microplastics exposure resulted in reduced acetylcholinesterase activity leading to elevated NO concentration along with altered serotonin and dopamine levels and subsequently leading to down-regulated bdnf gene expression and modulated downstream apoptotic signalling, confirming the neurotoxicity potential of microplastics causing neuronal dysfunction. This study also compared the binding affinities between styrene and human proteins (Bdnf, p53 and Bcl-2) using bioinformatics methods, and docking results showed negative binding energy resulting in high binding affinities of Bcl-2 then p53 and Bdnf with styrene.

Investigation of Nootropic and Neuroprotective Activity of Myristica malabarica Bark Extracts on STZ induced Cognitive Impairment in Experimental Animals

The present study aims to assess the Myristica malabarica Bark (MM) extracts in the diabetes-induced cognitive impaired rat model for its nootropic and neuroprotective activity. Memory enhancing activity was evaluated by Y maze and Morris water maze test, respectively. Neuroprotective effects of MM bark extracts were assessed by measuring the acetylcholinesterase, lipid peroxide, superoxide dismutase (SOD), total nitric oxide (NO), catalase (CAT) and glutathione (GSH) levels in the brain of diabetic rats. The Myristica malabarica bark methyl alcohol extract (MMMA) (100 and 200 mg/kg) was observed to affect a significant improvement in spontaneous alteration (P<0.01, P<0.001) and transfer latency (P< 0.01 P<0.001) in retention trials on Y maze and Morris water maze test respectively. However, a significant reduction in acetylcholinesterase activity (P<0.001), lipid peroxide (P<0.001), total NO (P< 0.001) and a substantial increase in SOD, CAT and GSH (P<0.001) levels was observed in animals treated with MMMA (200 mg/kg) related to the diabetic control group. The current results indicate that Myristica malabarica extracts were defending the cognitive decline in diabetes condition and which requires some additional studies to clarify its mode of action.

L-carnitine Modulates Cognitive Impairment Induced by Doxorubicin and Cyclophosphamide in Rats; Insights to Oxidative Stress, Inflammation, Synaptic Plasticity, Liver/brain, and Kidney/brain Axes.

Chemotherapy-induced cognitive impairment in cancer patients is known as "chemobrain". Doxorubicin and Cyclophosphamide are two chemotherapeutic agents used in combination to treat solid tumors. L-carnitine was reported for its anti-oxidant and anti-inflammatory activities. The goal of the present study was to elucidate the neuroprotective effect of L-carnitine against chemobrain induced by Doxorubicin and Cyclophosphamide in rats. Rats were divided into five groups: Control group; Doxorubicin (4mg/kg, IV) and Cyclophosphamide (40mg/kg, IV)-treated group; two L-carnitine-treated groups (150 and 300mg/kg, ip) with Doxorubicin and Cyclophosphamide; and L-carnitine alone-treated group (300mg/kg). Doxorubicin and Cyclophosphamide induced histopathological changes in rats' hippocampi and prefrontal cortices, as well as reduced memory as evidenced by behavioural testing. L-carnitine treatment showed opposite effects. In addition, chemotherapy treatment enhanced oxidative stress via reducing catalase and glutathione levels, and inducing lipid peroxidation. By contrast, L-carnitine treatment showed powerful antioxidant effects reversing chemotherapy-induced oxidative damage. Moreover, chemotherapy combination induced inflammation via their effect on nuclear factor kappa B(p65), interleukin-1β, and tumor necrosis factor-α. However, L-carnitine treatment corrected such inflammatory responses. Furthermore, Doxorubicin and Cyclophosphamide reduced synaptic plasticity via hindering expression of brain-derived neurotrophic factor, phosphorylated cyclase response element binding protein, synaptophysin, and postsynaptic density protein 95 whereas protein expression of such synaptic plasticity biomarkers was enhanced by L-carnitine treatment. Finally, acetylcholinesterase activity was found to be enhanced by chemotherapy treatment affecting rats' memory while L-carnitine treatment reduced acetylcholinesterase activity. L-carnitine also showed hepatoprotective and renal protective effects suggesting liver/brain and kidney/brain axes as possible mechanisms for its neuroprotective effects.

Memantine, an NMDA receptor antagonist, protected the brain against the long-term consequences of sepsis in mice

AimsLong-term neuroinflammation and brain dysfunction have frequently been reported in sepsis survivors. In this study, the protective effect of memantine (an NMDA receptor antagonist) on the long-term consequences of sepsis on the brain was investigated in mice. Materials and methodsEighty-five male C57 mice were included. Memantine was administrated through gavage at 5, 10, and 20 mg/kg three days before sepsis and continued for three days after sepsis induction. Sepsis was induced by intraperitoneal injection of 5 mg/kg LPS. A cohort of mice was sacrificed on the 4th day post sepsis to measure NF-κB, TNF-α, and IL-1β mRNA expression and oxidative stress markers in the brain. The second cohort was used for behavioral tests one month after sepsis induction and then sacrificed for oxidative stress markers and acetylcholinesterase (AChE) activity measurement. Key findingsMDA levels and mRNA expression of NF-κB, TNF-α, and IL-1β ameliorated by memantine at the early days of sepsis induction, and total thiol content and SOD activity were increased. Post-septic mice showed significant disruption of recognition memory in novel object recognition (NOR) and depressive and anxiety-like behaviors in tail suspension test, elevated plus maze (EPM), and open field tests one month after sepsis. Memantine at 10 and 20 mg/kg dose-dependently ameliorated behavioral abnormalities, reduced AChE activity and MDA levels, and enhanced SOD activity and thiol content one month after sepsis. SignificanceThese findings suggest that early treatment of septic mice with memantine could ameliorate brain inflammation and oxidative damage and prevent long-term behavioral consequences of sepsis.

Inorganic arsenic alters the development of dopaminergic neurons but not serotonergic neurons and induces motor neuron development via Sonic hedgehog pathway in zebrafish

The mechanism of inorganic arsenic-induced neurotoxicity at the cellular level is not known. In zebrafish, teratological effects of inorganic arsenic have been shown at various concentrations. Here, we used similar concentrations of inorganic arsenic to evaluate the effects on specific neuron types. Exposure of zebrafish embryos at 5 h post fertilization (hpf) to sodium arsenite induced developmental toxicity (reduced body length) in 72 hpf larvae, beginning at a concentration of 300 mg/L concentration. Mortality or overt morphological deformity was detected at 500 mg/L sodium arsenite. While 200 mg/L sodium arsenite induced development of tyrosine hydroxylase-positive (dopaminergic) neurons, there was no significant effect on the development of 5-hydroxytryptamine (serotonergic) neurons. Sodium arsenite reduced acetylcholinesterase activity. In the hb9-GFP transgenic larvae, both 200 and 400 mg/L sodium arsenite produced supernumerary motor neurons in the spinal cord. Inhibition of the Sonic hedgehog (Shh) pathway that is essential for motor neuron development, by Gant61, prevented sodium arsenite-induced supernumerary motor neuron development. Inductively coupled plasma mass spectrometry (ICP-MS) revealed that with 200 mg/L and 400 mg/L sodium arsenite treatment, each larva had an average of 387.8 pg and 847.5 pg arsenic, respectively. The data show for the first time that inorganic arsenic alters the development of dopaminergic and motor neurons in the zebrafish larvae and the latter occurs through the Shh pathway. These results may help understand why arsenic-exposed populations suffer from psychiatric disorders and motor neuron disease and Shh may, potentially, serve as a plasma biomarker of arsenic toxicity.

Effects of Phenolic-Rich Pinus densiflora Extract on Learning, Memory, and Hippocampal Long-Term Potentiation in Scopolamine-Induced Amnesic Rats.

Alzheimer's disease is the most common type of dementia with cognitive impairment. Various plant-derived phenolics are known to alleviate cognitive impairment in Alzheimer's disease by radical scavenging and strengthening synaptic plasticity activities. Here, we examined the cognition-improving effect of Pinus densiflora Sieb. et Zucc. bark extract (PBE). We identified and quantified phenolics in the PBE using a UHPLC-Orbitrap mass spectrometer. To evaluate the cognition-enhancing effects of PBE, scopolamine-induced amnesic Sprague-Dawley (SD) rats (5 weeks old) and ion channel antagonist-induced organotypic hippocampal slices of SD rats (7 days old) were used. Twenty-three phenolics were tentatively identified in PBE, 10 of which were quantified. Oral administration of PBE to the scopolamine-induced SD rats improved cognitive impairment in behavioral tests. PBE-fed SD rats showed significantly improved antioxidant indices (superoxide dismutase and catalase activities, and malondialdehyde content) and reduced acetylcholinesterase activity in hippocampal lysate compared with the scopolamine group. PBE increased the long-term potentiation (LTP) induction and rescued LTP from blockades by the muscarinic cholinergic receptor antagonist (scopolamine) and N-methyl-D-aspartate channel antagonist (2-amino-5-phosphonovaleric acid) in the organotypic hippocampal slices. These results suggest that polyphenol-rich PBE is applicable as a cognition-improving agent due to its antioxidant properties and enhancement of LTP induction.

Caffeine and Camellia sinensis enhance cognition and decrease acetylcholinesterase activity in scopolamine-induced memory loss in female Swiss mice

Caffeine and Camellia sinensis (green tea) has been known to have positive effect on memory. The present study investigated the possible effect of caffeine and green tea co-administration on oxidative stress markers, inflammatory marker and acetylcholine esterase activity in scopolamine-induced memory loss in female Swiss mice. Memory behavioral tests using Y-maze and Morris water maze was carried out, followed by oxidative stress biomarkers, acetylcholinesterase activity and Tumor Necrosis Factor alpha (TNF-α) evaluation from the mice brain tissues after caffeine and green tea administration. Scopolamine administered intraperitoneally at a dose of 1mg/kg Body Weight (BW) for 7 days significantly reduced the percent alternation of the mice in Y-maze thus, increased acetylcholinesterase activity and increased TNF-α level. However, caffeine administered orally at a dose 50mg/kg BW and green tea administered orally at a dose of 60mg/kg BW increased the percent alternation significantly, reduced acetylcholinesterase activity and reduced the TNF alpha level significantly. Oxidative stress markers evaluated GSH and MDA, showed no significant difference across all groups. These findings showed scopolamine has a deteriorating effect on cognition by increasing acetylcholinesterase activities thus mopping out acetylcholine at a faster rate. However, caffeine and green tea singly and in combination restored cognition, reduced acetylcholinesterase activity and restored TNF-α level. The neuroprotective effect of caffeine and green tea was compared to that of Donepezil, an established cognition enhancing drug and the effect was agonistic. The ability of caffeine and green tea to reduce acetylcholinesterase activity could be the mechanism for the ability to enhance memory. The ability of these compounds in restoring TNF alpha level also further potentiates their neuroprotective capability.

Nutraceutical potential of almond fruits in managing diabetes-related erectile dysfunction: Effect on Nrf-2 level and smooth muscle/collagen ratio.

Oxidative stress is one of the major crosstalk between diabetes and erectile dysfunction. Tropical almond is a natural antioxidant that works in a way to neutralize the effect of reactive oxygen species in disease management. This study therefore aimed to evaluate the effects of tropical almond on the nuclear factor erythroid-2-related factor-2 (nrf-2) level and smooth muscle/collagen ratio, as well as other biochemical indices in the penile tissue of diabetic rats. Six non-diabetic male rats (control) and 36 diabetic male rats were divided into six groups (n=6). The diabetic male rats were placed on almond-supplemented diets except for the diabetic control group. Thereafter, the rats were sacrificed penile tissues were excised for nrf-2, smooth muscle/collagen ratio, and other biochemical analyses. The results revealed a significant (p < 0.05) decrease in nrf-2 level, smooth muscle/collagen ratio, and total thiol level, with a concomitant increase in acetylcholinesterase activity in comparison to the control group. Interestingly, therapy with diets high in almond fruits significantly enhances the nrf-2 level, smooth muscle/collagen ratio, and total thiol level in comparison with the untreated diabetic group. In addition, dietary inclusion of almond fruits significantly reduced acetylcholinesterase activity in diabetic male rats. Therefore, the preventive management with almond fruits could be beneficial in combating erectile dysfunction associated with diabetes. The activities of almond fruits reported in this study could be due to their antioxidant property and the inherent phytoconstituents (amino acids, phenolic compounds, and flavonoids).

Toxicity assessment of SARS-CoV-2-derived peptides in combination with a mix of pollutants on zebrafish adults: A perspective study of behavioral, biometric, mutagenic, and biochemical toxicity

The dispersion of SARS-CoV-2 in aquatic environments via the discharge of domestic and hospital sewage has been confirmed in different locations. Thus, we aimed to evaluate the possible impacts of zebrafish (Danio rerio) exposure to SARS-CoV-2 peptide fragments (PSPD-2001, 2002, and 2003) alone and combined with a mix of emerging pollutants. Our data did not reveal the induction of behavioral, biometric, or mutagenic changes. But we noticed an organ-dependent biochemical response. While nitric oxide and malondialdehyde production in the brain, gills, and muscle did not differ between groups, superoxide dismutase activity was reduced in the “PSPD”, “Mix”, and “Mix+PSPD” groups. An increase in catalase activity and a reduction in DPPH radical scavenging activity were observed in the brains of animals exposed to the treatments. However, the “Mix+PSPD” group had a higher IBRv2 value, with NO levels (brain), the reduction of acetylcholinesterase activity (muscles), and the DPPH radical scavenging activity (brain and muscles), the most discriminant factors for this group. The principal component analysis (PCA) and hierarchical clustering analysis indicated a clear separation of the “Mix+PSPD” group from the others. Thus, we conclude that exposure to viral fragments, associated with the mix of pollutants, induced more significant toxicity in zebrafish adults than in others.

Pharmacological Investigations of Selected Multitarget‐Direct Ligands for the Treatment of Alzheimer's Disease

AbstractAlzheimer's disease (AD) is a complex, degenerative condition linked to memory loss and cognitive degradation. The phenyl sulfonyl‐pyrimidine derivatives containing dimethoxy‐chloro substituent (BS‐10 and BS‐22) were previously recognized as multitarget‐directed ligands (MTDLs) due to their ability to inhibit acetylcholinesterase (AChE) at low nanomolar concentrations (IC50=47.33±0.02 and 51.36±0.04 nM respectively) while also reducing amyloid beta (Aβ) aggregation. In the current investigation, we investigated the in vivo and ex‐vivo effects of BS‐10 and BS‐22 chemicals on cognition and the cholinergic system. We have used scopolamine and Aβ1‐42 models of cognitive impairment which were measured during Y‐maze and passive avoidance apparatus. Results showed that BS‐10 at 10 mg/kg compared to BS‐22 at 20 mg/kg rescued memory impairment more significantly. Moreover, ex‐vivo and biochemical studies exhibited both compounds improved the hippocampal acetylcholine (Ach) level by reducing AChE activity as well as antioxidant properties. In addition, BS‐10 and BS‐22 attenuated Aβ1‐42 induced cognitive deficiency in rats during Y‐maze tests and significantly restored mitochondrial membrane potential and reduced the tau protein level in rats (p&lt;0.05). In summary, our results indicated that MTDLs BS‐10 and BS‐22 would be a promising therapeutic approach in AD.

Neuroprotective potential of Cannabis sativa-based oils in Caenorhabditis elegans

Substances from the Cannabis sativa species, especially cannabidiol (CBD) and Delta-9-tetrahydrocannabinol (Δ9-THC), have attracted medical attention in recent years. The actions of these two main cannabinoids modulate the cholinergic nervous system (CholNS) involving development, synaptic plasticity, and response to endogenous and environmental damage, as a characteristic of many neurodegenerative diseases. The dynamics of these diseases are mediated by specific neurotransmitters, such as the GABAergic nervous system (GNS) and the CholNS. The nematode Caenorhabditis elegans is an important experimental model, which has different neurotransmitter systems that coordinate its behavior and has a transgene strain that encodes the human β-amyloid 1–42 peptide in body wall muscle, one of the main proteins involved in Alzheimer´s disease. Therefore, the objective of this study was to evaluate the protective potential of terpenoids found in C. sativa in the GNS and CholNS of C. elegans. The effect of two C. sativa oils with variations in CBD and THC concentrations on acetylcholinesterase (AChE) activity, lipid peroxidation, and behavior of C. elegans was evaluated. C. sativa oils were efficient in increasing pharyngeal pumping rate and reducing defecation cycle, AChE activity, and ROS levels in N2 strains. In the muscle:Abeta1-42 strain, mainly when using CBD oil, worm movement, body bends, and pharyngeal pumping were increased, with a reduced AChE activity. Consequently, greater investments in scientific research are needed, in addition to breaking the taboo on the use of the C. sativa plant as an alternative for medicinal use, especially in neurodegenerative diseases, which have already shown positive initial results.

Short-term exposure of the mayfly larvae (Cloeon dipterum, Ephemeroptera: Baetidae) to SARS-CoV-2-derived peptides and other emerging pollutants: A new threat for the aquatic environments

The input of SARS-CoV-2 or its fragments into freshwater ecosystems (via domestic or hospital sewage) has raised concerns about its possible impacts on aquatic organisms. Thus, using mayfly larvae [Cloeon dipterum (L.), Ephemeroptera: Baetidae] as a model system, we aimed to evaluate the possible effects of the combined short exposure of SARS-CoV-2-derived peptides (named PSPD-2001, PSPD-2002, and PSPD-2003 – at 266.2 ng/L) with multiple emerging pollutants at ambient concentrations. After six days of exposure, we observed higher mortality of larvae exposed to SARS-CoV-2-derived peptides (alone or in combination with the pollutant mix) and a lower-body condition index than those unexposed larvae. In the “PSPD” and “Mix+PSPD” groups, the activity of superoxide dismutase, catalase, DPPH radical scavenging activity, and the total thiol levels were also lower than in the “control” group. In addition, we evidenced the induction of nitrosative stress (inferred by increased nitrite production) and reduced acetylcholinesterase activity by SARS-CoV-2-derived peptides. On the other hand, malondialdehyde levels in larvae exposed to treatments were significantly lower than in unexposed larvae. The values of the integrated biomarker response index and the principal component analysis (PCA) results confirmed the similarity between the responses of animals exposed to SARS-CoV-2-derived peptides (alone and in combination with the pollutant mix). Although viral peptides did not intensify the effects of the pollutant mix, our study sheds light on the potential ecotoxicological risk associated with the spread of the new coronavirus in aquatic environments. Therefore, we recommend exploring this topic in other organisms and experimental contexts.

Evaluation of the neuroprotective activity of P. amarus in attenuating arsenic-induced neurotoxicity - an in vivo study

BackgroundArsenic is viewed as a bizarre and frightful element in human history. Recent studies showed that even low levels of arsenic can cause neurological damage. Phyllanthus amarus is an important medicinal herb proved to have neuro protective effect in experimental animals. This pre-clinical study used an animal model of arsenic toxicity and screened the different neuroprotective mechanisms of Phyllanthus amarus ethanolic extract. PurposeTo assess the effect of Phyllanthus amarus ethanolic extract on various biochemical parameter's in the brain of arsenic administered Wistar albino rats. MethodologyThe neuroprotective activity of P. amarus against arsenic induced toxicity was studied in Wistar albino rats. The experimental animals (n=24) were divided into four groups of 6 rats each. Rats in group I received distilled water, whereas rats in groups II, III, and IV received arsenic as sodium arsenite salt (40 mg/kg b.w) in drinking water daily for 28 days. In addition, rats from groups III, and IV also received P. amarus ethanolic extract 100 and 200 mg/kg b.w, by intragastric route, once daily for a period of 28 days. At the end of the experiment rats were subjected to various neurobehavioral tests such as Elevated plus maze, Light dark arena, Forced swim test and Tail suspension test. After 24 h of the last treatment, the animals were euthanized and brain tissue was assayed for various biochemical parameters. ResultsANOVA and Post hoc testing of behavioral and biochemical data (Dunnett's t-test and Student unpaired T test) showed co-administration of P. amarus ethanolic extract significantly reversed anxiety and depression-like behaviors in experimental animals. P. amarus ethanolic extract effectively reduced acetyl cholinesterase activity in the brain, and it also increased the levels of dopamine and serotonin in the brains of arsenic-treated animals as compared to only arsenic treated group. P. amarus ethanolic extract significantly decreased lipid peroxidase and increased brain catalase and super oxidase dismutase activities. ConclusionBased on the pharmacological, and biochemical analysis the plant extracts of P. amarus have shown protective effects against arsenic induced neurotoxicity.

Multiadducts of C60 Modulate Amyloid-β Fibrillation with Dual Acetylcholinesterase Inhibition and Antioxidant Properties: In Vitro and In Silico Studies.

Amyloid-β (Aβ) fibrils induce cognitive impairment and neuronal loss, leading to onset of Alzheimer's disease (AD). The inhibition of Aβ aggregation has been proposed as a therapeutic strategy for AD. Pristine C60 has shown the capacity to interact with the Aβ peptide and interfere with fibril formation but induces significant toxic effects in vitro and in vivo. To evaluate the potential of a series of C60 multiadducts to inhibit the Aβ fibrillization. A series of C60 multiadducts with four to six diethyl malonyl and their corresponding disodium-malonyl substituents were synthesized as individual isomers. Their potential on Aβ fibrillization inhibition was evaluated in vitro, in cellulo, and silico. Antioxidant activity, acetylcholinesterase inhibition capacity, and toxicity were assessed in vitro. The multiadducts modulate Aβ fibrils formation without inducing cell toxicity, and that the number and polarity of the substituents play a significant role in the adducts efficacy to modulate Aβ aggregation. The molecular mechanism of fullerene-Aβ interaction and modulation was identified. Furthermore, the fullerene derivatives exhibited antioxidant capacity and reduction of acetylcholinesterase activity. Multiadducts of C60 are novel multi-target-directed ligand molecules that could hold considerable promise as the starting point for the development of AD therapies.

Asiatic acid attenuates aluminium chloride-induced behavioral changes, neuronal loss and astrocyte activation in rats.

Aluminium (Al) is a potent neurotoxic metal known to cause neurodegeneration. Al exposure causes oxidative stress by accumulation of reactive oxygen species, followed by the activation of neuronal cell death in the brain. Asiatic acid (AA), the major bioactive compound of Centella asiatica (a medicinal plant), act as multifunctional drug as well as an antioxidant. Thus, the present study aimed to investigate the potential neuroprotective effect of AA against Al neurotoxicity. Rats were orally administered aluminium chloride (AlCl3; 100mg/kg b. wt.) dissolved in distilled water for 8 weeks or AA (75mg/kg b. wt.) in combination with AlCl3. The results showed that AlCl3-intoxication causes significant impairment of memory, enhances anxiety-like behavior, acetyl cholinesterase (AChE) activity, malondialdehydes (MDA) level, and concomitant decrease in the activities of superoxide dismutase (SOD) and catalase (CAT) in the cortex and hippocampus regions of rat brain. In addition, AlCl3-intoxication enhanced neuronal loss and reactive astrogliosis in both regions. However, co-administration of AA with AlCl3 significantly attenuated the behavioral alterations, restored SOD and CAT activities, while reduced AChE activity and MDA content. Further, the study demonstrated that AA attenuates neuronal loss and reactive astrogliosis in rat brain. In conclusion, the study suggests that AA protects rat brain from Al neurotoxicity by inhibiting oxidative stress, neuronal loss and reactive astrogliosis.

Field mixtures of currently used pesticides in agricultural soil pose a risk to soil invertebrates

Massive use of pesticides in conventional agriculture leads to accumulation in soil of complex mixtures, triggering questions about their potential ecotoxicological risk. This study assessed cropland soils containing pesticide mixtures sampled from conventional and organic farming systems at La Cage and Mons, France. The conventional agricultural field soils contained more pesticide residues (11 and 17 versus 3 and 11, respectively) and at higher concentrations than soils from organic fields (mean 6.6 and 10.5 versus 0.2 and 0.6 μg kg−1, respectively), including systemic insecticides belonging to neonicotinoids, carbamate herbicides and broad-spectrum fungicides mostly from the azole family. A risk quotient (RQi) approach evaluated the toxicity of the pesticide mixtures in soil, assuming concentration addition. Based on measured concentrations, both conventional agricultural soils posed high risks to soil invertebrates, especially due to the presence of epoxiconazole and imidacloprid, whereas soils under organic farming showed negligible to medium risk. To confirm the outcome of the risk assessment, toxicity of the soils was determined in bioassays following standardized test guidelines with seven representative non-target invertebrates: earthworms (Eisenia andrei, Lumbricus rubellus, Aporrectodea caliginosa), enchytraeids (Enchytraeus crypticus), Collembola (Folsomia candida), oribatid mites (Oppia nitens), and snails (Cantareus aspersus). Collembola and enchytraeid survival and reproduction and land snail growth were significantly lower in soils from conventional compared to organic agriculture. The earthworms displayed different responses: L. rubellus showed higher mortality on soils from conventional agriculture and large body mass loss in all field soils, E. andrei showed considerable mass loss and strongly reduced reproduction, and A. caliginosa showed significantly reduced acetylcholinesterase activity in soils from conventional agriculture. The oribatid mites did not show consistent differences between organic and conventional farming soils. These results highlight that conventional agricultural practices pose a high risk for soil invertebrates and may threaten soil functionality, likely due to additive or synergistic “cocktail effects”.

Long-Term Effect of Porcine Brain Enzyme Hydrolysate Intake on Scopolamine-Induced Memory Impairment in Rats.

No study has revealed the effect of porcine brain enzyme hydrolysate (PBEH) on memory impairment. We aimed to examine the hypothesis that PBEH intake modulates memory deficits and cognitive behavior in scopolamine (SC)-induced amnesia rats, and its mechanism, including gut microbiota changes, was determined. Sprague–Dawley male rats had intraperitoneal injections of SC (2 mg/kg body weight/day) at 30 min after daily feeding of casein (MD-control), PBEH (7 mg total nitrogen/mL) at 0.053 mL (Low-PBEH), 0.159 mL (Medium-PBEH), 0.478 mL (High-PBEH), or 10 mg donepezil (Positive-control) per kilogram body weight per day through a feeding needle for six weeks. The Normal-control rats had casein feeding without SC injection. PBEH dose-dependently protected against memory deficits determined by passive avoidance test, Y-maze, water-maze, and novel object recognition test in SC-induced rats compared to the MD-control. The High-PBEH group had a similar memory function to the Positive-control group. Systemic insulin resistance determined by HOMA-IR was lower in the PBEH groups than in the Normal-control but not the Positive-control. In parallel with systemic insulin resistance, decreased cholesterol and increased glycogen contents in the hippocampus in the Medium-PBEH and High-PBEH represented reduced brain insulin resistance. PBEH intake prevented the increment of serum TNF-α and IL-1β concentrations in the SC-injected rats. Hippocampal lipid peroxide and TNF-α contents and mRNA TNF-α and IL-1β expression were dose-dependently reduced in PBEH and Positive-control. PBEH decreased the hippocampal acetylcholinesterase activity compared to the MD-control, but not as much as the Positive-control. PBEH intake increased the α-diversity of the gut microbiota compared to the MD-control, and the gut microbiota community was separated from MD-control. In metagenome function analysis, PBEH increased the energy metabolism-related pathways of the gut microbiota, including citric acid cycle, oxidative phosphorylation, glycolysis, and amino acid metabolism, which were lower in the MD-control than the Normal-control. In conclusion, alleviated memory deficit by PBEH was associated potentially with not only reducing acetylcholinesterase activity but also improving brain insulin resistance and neuroinflammation potentially through modulating gut microbiota. PBEH intake (1.5–4.5 mL of 7 mg total nitrogen/mL for human equivalent) can be a potential therapeutic agent for improving memory impairment.

Acute Toxicity Test and Nootropic Activity of Ethanolic Extract of Astragalus membranaceus Bunge on Scopolamine-Induced Amnesia in Rats

The dried roots of Astragalus membranaceus Bunge, belongs to the family fabaceae enhances the memory function and this could be mediated through brain cholinergic system. Historically in China it is used as a medicine for treatment of different types of diseases. It gives good protection against aging and age related diseases. Astragalus membranaceus Bunge root extract was investigated to reveal its nootropic effect and acute toxicity study. The powdered roots were tested for the phytochemical constituents. Carbohydrates, proteins, amino acids, glycosides, saponins, volatile oils, alkaloids, sterols and flavonoids were present. The acute toxicity study of ethanolic extract was carried out according to the OECD test guideline 423. There were no signs of toxicity of rats even with a maximum dose of 2000 mg/kg of the extract during 14 days. For evaluation of nootropic activity, ethanolic extract was administered by oral route to scopolamine induced amnesic rat model. The reduction of acetylcholinesterase activity in the rat brain supports the elevated plus maze (EPM) and passive avoidance test by improving memory function by lowering acetylcholinesterase activity. Present study shows Astragalus membranaceus Bunge root extract possesses significant nootropic activity in scopolamine induced amnesia rat models.&#x0D; Keywords: Astragalus membranaceus Bunge, EPM, passive avoidance, nootropic, acetyl Cholinesterase and Scopolamine.

Jobelyn® extends the life span and improves motor function in Drosophila melanogaster exposed to lipopolysaccharide via augmentation of antioxidant status.

Jobelyn® (JB), a dietary supplement, derived from polyphenol-rich leaf sheath of Sorghum bicolor, has been reported to attenuate sensorimotor deficits and oxidative stress evoked by complete Freund-adjuvant in mice. This present study evaluated its effects on the life span, motor function and changes in oxidative stress parameters as well as acetylcholinesterase activity in Drosophila melanogaster exposed to lipopolysaccharide (LPS). The flies (50 per vial), in 5 replicates were fed with LPS (250μg/kg diet) alone or in combination with JB (0.25-1.0mg/kg diet) daily for 7days. The mortality rate and motor function were evaluated on day 7. The flies were afterwards processed for determination of oxidative stress parameters and acetylcholinesterase activity. The effects of JB (0.25-1.0mg/g diet) on the longevity of Drosophila was also investigated wherein the flies were monitored daily for mortality throughout their lifespan. The flies exposed to LPS (250μg/kg diet) had reduced life span and elevated oxidative stress when compared with control. However, JB (0.25 and 1.0mg/kg diet) improved the motor function and also reduced the mortality rate of the flies exposed to LPS. It also restored the cellular antioxidant status and reduced acetylcholinesterase activity, accumulation of hydrogen peroxide as well as nitric oxide in Drosophila fed with LPS. JB also extended the longevity of the fliesrelative to control. The findings that JB improves motor function and extended the lifespan of Drosophila flies by boosting the antioxidant status and cholinergic function, suggest it might be helpful in delaying the onset of neuropsychiatric illnesses associated with the aging processes.