Passive Shock Avoidance Research Articles

Dihydroxytrimethoxyflavone possess memory improvement effects against scopolamine in mice via modulating multiple pathways: In‐silico and in‐vivo evidences

AbstractBackgroundDementia is a deliberating neurodegenerative disorder which causes impairment of intellectual functions. The USFDA approved drugs has limited efficacy and numerous side effects. Thus, finding newer drugs to manage dementia and cognitive disorders is certainly required. The present study explores the potential of a natural flavone, 5,7‐dihydroxy‐3',4',5'‐trimethoxyflavone (DHF), as memory enhancer drug against scopolamine‐induced cognitive deficit in mice.MethodsAnimals were treated with DHF (5‐10 mg/kg, p.o.) for 7 days after inducing cognitive impairment by scopolamine (1mg/kg,i.p.). Memory functions (passive shock avoidance task and Morris Water Maze), brain acetylcholinesterase (AChE) activity, inflammatory markers, oxidative stress, apoptotic biomarkers and histopathological studies (H&E and congo red staining for beta amyloid) were determined to measure memory improvement effects of DHF. In‐silico (molecular docking) studies were performed to understand the interactions of DHF with key pathological enzymes related to dementia.ResultsTreatment of scopolamine administered mice with DHF improved scopolamine‐induced cognitive impairment and restore brain biochemical parameters (inhibited acetylcholinesterase activity, enhanced glutathione levels, and reduced TBARS, TNF‐α, IL‐6, IL‐1β and caspase‐3 levels). Moreover, histopathological studies showed that DHF treatment reduced the neuronal cell death and amyloid depositions in mice brain. Further, molecular docking studies revealed string interactions of DHF with crucial amino acids of AChE and caspase‐3.ConclusionThese results suggest that DHF was effective in treating scopolamine induced cognitive deficit by improving cerebral cholinergic dysfunction and reducing brain oxidative stress, inflammation, apoptosis and beta‐amyloid depositions in mice. Thus, DHF could be developed as a potential alternative drug to treat memory disorders.

Memory improvement effects of Ganoderma mediosinense in mice via its anticholinergic and antioxidant activities

AbstractBackgroundSpecies of the genus Ganoderma are valued both for their medicinal as well as nutritional properties. Traditionally, these are employed in neurological disorders. However, G. mediosinense has not been evaluated for anti‐amnesic effects previously. Therefore the present study is aimed to explore the cognitive improvement effects of the G. mediosinense extract (GME) against mouse model of scopolamine induced amnesia.MethodAnimals were orally administered with GME (200, 400 and 800 mg/kg) for 7 consecutive days and amnesia was induced by scopolamine (1 mg/kg, i.p.) after 30 min of treatment. Cognitive functions were determined by employing passive shock avoidance task and novel object recognition test. Brain AChE and lipid peroxidation were determined to have an insight into the associated neuroprotective mechanism of GME.ResultTreatment with GME showed dose dependent amelioration of cognitive deficit induced by scopolamine in animals. Also, GME reduced the brain AChE activity and oxidative stress.ConclusionThese results indicated the anti‐amnesic effects of GME via decreasing brain cholinergic and oxidative stress.

Evaluation of nootropic activity of telmisartan and metformin on diazepam-induced cognitive dysfunction in mice through AMPK pathway and amelioration of hippocampal morphological alterations

Cognitive impairments such as dementia are considered the biggest challenges for public health. Benzodiazepines are often prescribed for treatment of anxiety disorder but they are associated with elevated risk of dementia. The present study has been designed to evaluate the neuroprotective effect of telmisartan and metformin on diazepam-induced cognitive dysfunction in mice. Piracetam was used as an established nootropic agent. Mice were divided into 8 groups, group1; control group which received normal saline. groups 2, 3 and 4 were received telmisartan 0.3 mg/kg/day, metformin 100 mg/kg/day and piracetam 200 mg/kg/day respectively. group 5; DZP group that injected with diazepam 2.5 mg/kg, groups 6, 7 and 8 were received diazepam 2.5 mg/kg + telmisartan 0.3 mg/kg/day, metformin 100 mg/kg/day and piracetam 200 mg/kg/day respectively. All drugs were administrated for 15 successive days. Cognitive skills of the animals were examined with Elevated plus maze and Passive Shock Avoidance tests. Investigations of oxidative stress markers were performed. Gene expression levels of TNF-α, NFκB, Caspase 3 and AMPK were analyzed using RT-PCR. Histological and immunohistochemical techniques were performed in hippocampus using H&E, cresyl violet stain, anti GFAP and anti COX-2 immunostain. The study revealed that administration of diazepam increased initial and retention transfer latency as well as it decreased step down latency that means it caused memory impairment. There was a significant increase in hippocampal expression levels of TNF-α, NFκB, and Caspase 3 and downregulation of AMPK expression levels associated with increased neurodegeneration, astrocytes activation and COX-2 immunohistochemical staining. This study indicates that diazepam caused a decline in cognitive function depending on hippocampal activity. Telmisartan, a common antihypertensive agent and metformin, a traditional antidiabetic drug improved this cognitive dysfunction through their anti-oxidant and anti-inflammatory effect as they decreased initial and retention transfer latency as well as it increased step down latency. Also they decreased TNF-α, NFκB, and Caspase 3 and upregulated AMPK expression, moreover they ameliorated the hippocampal morphological alterations, GFAP and COX-2 immunoexpression.

Anti-Amnesic Effect of Curculigo orchioides Plant Extract and Its Function on Acetylcholinesterase Enzyme

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, and one of the most predominant causes of dementia in older people. Preventing acetylcholine from breakdown by an excess amount of acetylcholinesterase is a proven therapy for AD. Traditionally Curculigo orchioides is known for its antioxidant activity, enzyme inhibition activity, and other medicinal uses. In this study, in vitro acetylcholinesterase, inhibitory activity was investigated, and methanolic extract of the plant showed significant activity. This study aims to investigate cholinesterase inhibitory activity, learning, and memory-enhancing activity of Curculigo orchioides.
 Materials and Methods: The crude methanol extract of the dried powder was prepared by the cold extraction method. In-vitro acetylcholinesterase (AChE) inhibitory activities were determined by the modified Ellman’s method. To confirm learning and memory-enhancing effects, the scopolamine-induced memory impairment Swiss-albino mice were used, and to find the anti-amnesic effect of the extract, a passive shock avoidance task was applied.
 Results: Results proved that scopolamine-induced cognitive dysfunction decreased significantly by administration of the plant extract solution in the passive avoidance task, and inhibited brain acetylcholinesterase activity. While running an in-vitro AChE inhibitory test the IC50 was 0.782±0.067μg/ml.
 Conclusion: The results suggested that methanolic extract of Curculigo orchioides can inhibit AChE in-vitro. Besides this, it provides data that proves its ability to improve whole brain AChE activity and enhance memory.

Improvement of cognitive function in mice by Citrus reticulata var. kinnow via modulation of central cholinergic system and oxidative stress.

Memory disorders are a result of a number of factors, of which elevated brain oxidative stress and acetylcholinesterase (AChE) activity are significant hallmarks. A number of Citrus species have cognition-enhancing capacity mediated by their antioxidant and anti-cholinesterase activities. This study was designed to assess the cognitive-enhancing, antioxidant and anticholinesterase potentials of Citrus reticulata var. kinnow (CR) leaf extracts. CR extracts were examined by bioactivity guided fractionation using in-vitro DPPH and Ellman assays to determine antioxidant and AChE inhibitory capacity. The most active component was further evaluated for memory improvement effects using mouse model of scopolamine induced amnesia. Passive shock avoidance test and elevated plus maze test were employed to determine cognitive functions while brain biochemical parameters were measured to establish the neuroprotective mechanism. The methanol extract (ME) showed marked AChE inhibitory and antioxidant activities, therefore, it was fractionated. Comparative analysis of all obtained fractions revealed that ethylacetate fraction (EAF) was most active. Both ME and EAF improved cognitive dysfunction caused by scopolamine in mice by reducing TBARS levels and brain AChE activity. TLC densitometric studies showed appreciable levels of naringenin in ME (0.32 % w/w) and EAF (1.14 % w/w). The observed memory enhancement effects of ME and EAF could be attributed to their ability to inhibit AChE activity and antioxidant effects due to presence of flavonoids.

Learning and Memory Enhancing Effects of BacoLive andreg; (An Enriched Composition of Bacopa monnieri Extract) in Scopolamine Induced Memory Impaired Mice

Objective: The objective of this study was to evaluate the learning and memory enhancement activity of BacoLive® (a composition enriched with bacosides from Bacopa monnieri) in various experimental models i.e., passive shock avoidance test, Y- maze test and novel object recognition test. Methodology: BacoLive® was administered for 7 days at the dose of 100, and 200 mg/kg to mice in passive shock avoidance test, Y-Maze test and in novel object recognition test. Scopolamine (0.5 mg/kg) was used to induce memory (amnesia) loss and piracetam (200 mg/kg) served as reference standard. After 7 days, cognitive and memory scales were measured as per standard test protocols. Results: In the passive shock test for memory, BacoLive ® reduced the latency to reach the shock free zone compared to amnesia induced group. In the Y-maze test, the number of arm entries failed to memorize the new space was decreased with BacoLive ® group compared to amnesia induced group. In the new object recognition test, BacoLIve ® improved the percentage preference for new object recognition compared to amnesia induced group. Conclusion: Based on the present study and findings, BacoLive® demonstrated learning and memory enhancing effects and reversed memory loss effects induced by scopolamine in mice, which suggest its beneficial role in conditions associated with memory and learning dysfunctions. Study indicates that bacopa extract justifies its traditional use in Ayurveda for memory related complications associated with neuro degeneration and stress.

Cerebroprotective effects of D. triquetrum on sodium nitrite‐induced hypoxia and ethanol‐induced neurodegeneration in animal models relevant to dementia

AbstractBackgroundCognitive impairment is a multidimensional and complicated concept that subsumes the attention, concentration, learning, memory, problem‐solving ability, visuospatial abilities, mental flexibility, psychomotor efficiency and manual dexterity.ObjectiveTo study the effects of aqueous extracts of roots of Desmodium triquetrum on cognitive deficit mice.MethodsAqueous extracts of Desmodium triquetrum (DTE) were screened for Sodium nitrite induced hypoxia and Ethanol induced neurodegeneration using behavioral models such as rotarod, Passive shock avoidance paradigm, special water bottle case model, elevated plus maze and Morris water maze. DTE (5, 2.5 and 1.25 mg/kg p.o.) were administered to the mice. Acquisition, retention, Transfer latency (TLT), Time spent in target quadrant (TSTQ), Step down latency (SDL) and Escape latency (ELT) and biochemical parameters such as AChE, MAOA, TBARS, epinephrine, 5 HT were determined. DNA fragmentation studies were conducted which were compared with Donepezil.ResultsDTE (5, 2.5 and 1.25 mg kg(‐1) p.o.) significantly (p < 0.001) protected the Sodium nitrite induced memory impairment by decreasing the time require to find the water bottle in special water bottle case model. DTE improved acquisition and retention memory significantly (p < 0.001) by decreasing the Transfer Latency Time (TLT), escape latency time, TSTQ and increased the Step Down Latency (SDL. DTE inhibited Acetylcholinestrase (p < 0.01) activity, increased GSH, decreased TBARS and inhibited MAOA activity. Reduced the metabolism of epinephrine, 5‐HT. DTE (5 mg kg‐1) protected the DNA fragmentation of frontotemporal cortex from hypoxic effects.ConclusionDesmodium triquetrum are beneficial in the management of Neurodegenerative disorders particularly for Alzheimer’s disease.

Curcumin loaded nanoparticles reversed monocrotophos induced motor impairment and memory deficit: Role of oxidative stress and intracellular calcium level

Monocrotophos is one of the extensively used organophosphorus insecticides in agriculture and animal husbandry in India. It induces neurotoxicity by inhibiting acetyl cholinesterase enzyme and elevating oxidative stress. Curcumin, dietary polyphenol, well known for its antioxidant and anti-inflammatory properties which could elicit protective effect against monocrotophos induced neurobehavioural abnormalities. Therefore this study is aimed to investigate ameliorative effect of curcumin loaded Nanoparticles on monocrotophos induced neurotoxicity.Curcumin loaded PLGA nanoformulation was prepared using nanoprecipitation technique and was characterized using zeta sizer, FTIR and NMR spectroscopy. For in-vivo study, 30 male rats were utilized. Exposure of monocrotophos was done at 2 mg/kg (p.o.) for 28 days. Curcumin bulk and cucurmin loaded Nanoparticles were administered with or without monocrotophos. Effect of monocrotophos exposure on behavioural changes was assessed by analysing spontaneous locomotor activity, motor coordination in rotarod test and contextual fear memory in passive shock avoidance paradigm. Effect on biochemical alteration in blood and brain were estimated.The average particle size of Curcumin loaded Nanoparticles was 114.9 nm and in-vitro release study suggested suitable release of Curcumin in simulated intestinal fluid. Results of in-vivo study indicated, monocrotophos exposure caused a significant increase in reactive oxygen species, thiobarbituric acid reactive substances, and intracellular free calcium levels along with altered behavioural abnormalities in locomotor activity, motor coordination, learning and memory. Decline in antioxidant defence level might suggest reduced host defence response. Treatment with curcumin alone did not significantly reversed monocrotophos induced neurotoxicity in rats. Whilst, treatment with curcumin loaded nanoparticles significantly reduced monocrotophos induced behavioural and biochemical alteration in rat brain.The outcome of the present study suggested improved efficacy of curcumin loaded nanoparticles, possibly via its enhanced bioavailability. Further alleviation of oxidative stress and intracellular free Ca2+ level might be speculated as one of the plausible neuroprotective mechanism of curcumin in this study.

Lawsonia Inermis Markedly Improves Cognitive Functions in Animal Models and Modulate Oxidative Stress Markers in the Brain.

Background and Objective: Medicinal plants represent an important source of alternative medicine for the management of various diseases. The present study was undertaken to assess the potential of Lawsonia inermis ethanol (Li.Et) and chloroform (Li.Chf) extracts as memory-enhancing agents in experimental animals. Materials and Methods: Li.Et and Li.Chf were phytochemically characterized via gas chromatography-mass spectroscopy (GC-MS). Samples were tested for nootropic potentials at doses of 25, 50, 100, 200 mg/kg (per oral in experimental animals (p.o.)). Swiss albino mice of either sex (n = 210) were divided into 21 × 10 groups for each animal model. Memory-enhancing potentials of the samples were assessed using two methods including “without inducing amnesia” and “induction of amnesia” by administration of diazepam (1 mg/kg, intraperitoneally. Piracetam at 400 mg/kg (i.p.) was used as positive control. Cognitive behavioral models including elevated plus maze (EPM) and the passive shock avoidance (PSA) paradigm were used. Biochemical markers of oxidative stress such as glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) levels were analyzed in the brain tissue of treated mice. Results: In 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals scavenging assay, Li.Et and Li.Chf exhibited 70.98 ± 1.56 and 66.99 ± 1.76% inhibitions respectively at 1.28 mg/mL concentration. GCMS results revealed the presence of important phytochemicals. Both samples (Li.Et and Li.Chf) at 25 mg/kg (p.o.) dose significantly (p < 0.05) improved learning and memory as indicated by decline in transfer latency and increase in step down latency in EPM and PSA models respectively. Li.Et and Li.Chf at 25 mg/kg (p.o.) showed considerable increase in GSH (2.75 ± 0.018 ***), SOD (2.61 ± 0.059 ***) and CAT (2.71 ± 0.049 ***) levels as compared to positive and negative control groups. Conclusions: This study provides the preliminary clue that L. inermis may be a potential source of memory-enhancing and anti-oxidant compounds and thus warrant further studies.

Nootropic Activity of Moringa oleifera Leaves

Objective: To study the nootropic activity of leaves of Moringa oleifera . Methods: Toluene-ethylacetate fraction of methanolic extract of Moringa oleifera (MOE) leaves was assessed for its nootropic activity using passive shock avoidance paradigm and elevated plus maze. MOE ( 50 and 100 mg/kg ) was compared with Piracetam (100 mg/kg ). Scopolamine (1 mg/kg) was used to induce cognitive dysfunction. The extract was also studied for its effect on gross behaviour. Results: MOE (50 and 100 mg/kg ) significantly decreased Transfer Latency(TL) on Day 2. The extract reduced the latency to reach the SFZ and the number of mistakes. No adverse effects were observed upto a dose of 200 mg/kg. Conclusion: Thus the leaves of Moringa oleifera possess a potential for exploring the nootropic principle.

Anti-amnesic effects of Ganoderma species: A possible cholinergic and antioxidant mechanism

Mushrooms are valued for their nutritional as well as medicinal properties. Ganoderma species are used traditionally to treat neurological disorders but scientific evidence for this is insufficient. The present study was designed to systematically evaluate the anti-amnesic effect of selected Ganoderma species i.e. G. mediosinense and G. ramosissimum. Extracts of selected mushroom species were evaluated for their antioxidant activity and acetylcholinesterase (AChE) inhibition using in-vitro assays (DPPH and Ellman tests respectively). The anti-amnesic potential of the most active extract (i.e. 70% methanol extract of G. mediosinense) was confirmed using mouse model of scopolamine-induced amnesia. Mice were treated with bioactive extract and donepezil once orally before the induction of amnesia. Cognitive functions were evaluated using passive shock avoidance (PSA) and novel object recognition (NOR) tests. The effect on brain AChE activity, brain oxidative stress (TBARS level) and neuronal damage (H & E staining) were also assessed. In-vitro results showed strong antioxidant and AChE inhibitory activities by G. mediosinense extract (GME). Therefore, it was selected for in-vivo studies. GME pre-treatment (800mg/kg, p.o.) reversed the effect of scopolamine in mice, evident by significant decrease (p <0.05) in the transfer latency time and increase in object recognition index in PSA and NOR, respectively. GME significantly reduced the brain AChE activity and oxidative stress. Histopathological examination of brain tissues showed decrease in vacuolated cytoplasm and increase in pyramidal cells in brain hippocampal and cortical regions. GME exerts anti-amnesic effect through AChE inhibition and antioxidant mechanisms.

Agmatine for combined treatment of epilepsy, depression and cognitive impairment in chronic epileptic animals

Epilepsy is fourth most common neurological disorders associated with depression and cognitive deficits. As per present scenario, none of the antiseizure drugs have been reported successful to have ameliorative effect on epilepsy associated depression and cognitive deficits. Thus, the study was envisioned to assess an ameliorative potential of agmatine on epilepsy and its efficacy and safety for management of associated depression and cognitive deficits. The animals were made epileptic employing pentylenetetrazole (35mg/kg i.p. every 48±2h) kindling model of epilepsy and subsequently were treated with vehicle, valproic acid (300mg/kg/day i.p.) and agmatine (2.5, 5, and 10mg/kg)/day/i.p. for 15days. Except naïve, all the groups were challenged with same pentylenetetrazole dose as employed during kindling on days 5, 10, and 15 to evaluate seizure severity. Two hours after seizure severity test, tail suspension test and passive shock avoidance paradigm was employed to evaluate depression and cognitive behavior respectively. Results suggested that epileptic animals were significantly associated with depression and cognitive impairment. Chronic valproate treatment significantly reduced seizure severity, but was found unable to mitigate depression and cognitive deficits. However, agmatine treatment dose dependently ameliorated seizure severity as well as associated depression and cognitive deficits. On 15th day, animals were euthanized and pertinent neurochemical estimations were carried out in cortical and hippocampal areas of the mice brain. Thus, study concluded that agmatine ameliorated seizure severity, depression and cognitive impairment in epileptic animals, possibly via restoring glutamate-GABA neurotransmission and serotonin synthesis with decreased nitrosative stress.

Evaluation of anti-amnesic effect of extracts of selected Ocimum species using in-vitro and in-vivo models

Ethnopharmacological relevanceOcimum species are traditionally used for the treatment of anxiety, nerve pain, convulsions and a variety of neurodegenerative disorders. The present study was undertaken to evaluate the anti-amnesic effect of O. basilicum L., O. sanctum L. and O. gratissimum L. extracts using in-vitro and in-vivo models. Materials and methodsIn-vitro acetylcholinesterase (AChE) inhibitory and antioxidant activities of hydro-methanol extracts of plants were evaluated using Ellman and DPPH and FRAP assays, respectively. The most active extract i.e. O. basilicum extract (OBE) was further explored for the possible anti-amnesic activity in mouse model of scopolamine induced amnesia using behavioral models (elevated plus maze and passive shock avoidance task). Brain AChE activity, oxidative profile and histopathological studies were assessed to outline the anti-amnesic mechanism of the extract. ResultsSignificant antioxidant and AChE inhibition activity was observed with all prepared extracts and however, OBE showed most marked free radical scavenging, reducing power and AChE inhibition (IC50 0.65±0.15mg/ml) activity. Basil leaves were standardized with respect to content of 7 phenolic acids using a HPLC-PDA method. A TLC densitometric method was employed to determine the quercetin content in the leaves. The in-vivo studies showed that OBE pre-treatment (200 and 400mg/kg, p.o.) reversed the memory deficit induced by scopolamine in mice, evident by significant (p<0.05) decrease in the transfer latency time and increase in step down latency in elevated plus maze and passive shock avoidance task, respectively. Moreover, OBE significantly reduced the brain AChE activity and oxidative stress. Further, histopathological examination of brain tissues displayed decrease in vacuolated cytoplasm and increase in pyramidal cells in hippocampal and cortical regions with OBE pre-treatment. ConclusionOBE possesses antioxidant and AChE inhibitory activity. These biochemical changes are responsible for the anti-amnesic and neuroprotective activities of O. basilicum which may be attributed to the presence of phenolic and flavonoid compounds. This can be developed as an effective anti-amnesic drug.

Asparagus adscendens root extract enhances cognition and protects against scopolamine induced amnesia: An in-silico and in-vivo studies

Asparagus adscendens Roxb. commonly known as safed musli and belonging to the Liliaceae family is cultivated mainly in Asian countries. In traditional medicine, safed musli is recommended as nerve tonic and remedy for memory impairment. The present study was aimed to evaluate nootropic and antiamnesic activities of Asparagus adscendens extract (AAE) using in silico and in vivo approach. Phytoconstituents of A. adscendens root reported in literature were subjected to in silico prediction using PASS and Pharmaexpert. The radial arm maze and passive shock avoidance paradigm were employed to evaluate nootropic activity. Subsequently, the anti-amnesic activity was evaluated in scopolamine induced amnesia model. To elucidate the mechanism of nootropic activity, the effect of AAE on the activities of acetylcholinesterase and antioxidant enzymes in the cortex and hippocampus of mice were also evaluated. In silico activity spectrum for all of A. adscendens phytoconstituents exhibited excellent prediction score for nootropic activity. Pretreatment with AAE (50, 100 & 200 mg/kg, i.p.) for 15 days showed significant decrease in working memory error, reference memory error and retrieval latency in radial arm maze and decrease in step down latency in passive shock avoidance paradigm were observed. Further, AAE significantly reduced acetylcholinesterase and oxidative stress parameters in cortex and hippocampus of mice. Thus, in silico and in vivo results suggest that A. adscendens root may exert its nootropic activity through both anti-acetylcholinesterase and antioxidant activities.

Protective Effect of Nerolidol Against Pentylenetetrazol-Induced Kindling, Oxidative Stress and Associated Behavioral Comorbidities in Mice

The present study was aimed to investigate the effect of nerolidol on the development of kindling and associate oxidative stress and behavioral comorbidities. Kindling was induced by repeated injections of a sub-convulsive dose of pentylenetetrazol (PTZ-35mg/kg; i.p.), at an interval of 48 ± 2h for 43days (21 injections). Nerolidol was administered daily in three doses (12.5, 25 and 50mg/kg) along with alternate day PTZ injection. To access behavioral comorbidities, animals were subjected to tail suspension test (TST) and passive shock avoidance (PSA) test to evaluate the associated depression and memory impairment respectively on the last day of PTZ administration. Following behavioral assessment, neurotransmitter level and oxidative stress markers were evaluated in brain. The results showed that nerolidol significantly suppressed the progression of kindling. Also, nerolidol ameliorates the kindling associated depression and memory impairment as indicated by decreased immobility time and increased step down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complimented with corresponding neurochemical and oxidative stress markers changes. In conclusion, the results of present study showed that nerolidol treatment has protective effect against PTZ-induced kindling and associated oxidative stress and behavioral comorbidities.

CEREBROPROTECTIVE EFFECTS OF GANGETIN ALKALOIDS ON SODIUM NITRITE-INDUCED HYPOXIA AND ETHANOL-INDUCED NEURODEGENERATION

Cognitive impairment is a multidimensional and complicated concept that subsumes the attention, concentration, learning, memory, problem-solving ability, visuospatial abilities, mental flexibility, psychomotor efficiency and manual dexterity. Objective: To study the effects of Gangetin alkaloids from the seeds of Desmodium gangeticum on cognitive deficit mice. Gangetin alkaloids were screened for Sodium nitrite induced hypoxia and Ethanol induced neurodegeneration using behavioral models such as rotarod, Passive shock avoidance paradigm, special water bottle case model, elevated plus maze and Morris water maze. GA (5, 2.5 and 1.25 mg/kg p.o.) were administered to the mice. Acquisition, retention, Transfer latency (TLT), Time spent in target quadrant (TSTQ), Step down latency (SDL) and Escape latency (ELT) and biochemical parameters such as AChE, MAOA, TBARS, epinephrine, 5 HT were determined. DNA fragmentation studies were conducted which were compared with donepezil. GA (5, 2.5 and 1.25 mg kg(-1) p.o.) significantly (p < 0.001) protected the Sodium nitrite induced memory impairment by decreasing the time require to find the water bottle in special water bottle case model. GA improved acquisition and retention memory significantly (p < 0.001) by decreasing the Transfer Latency Time (TLT), escape latency time, TSTQ and increased the Step Down Latency (SDL. GA inhibited Acetylcholinestrase (p < 0.01) activity, increased GSH,decreased TBARS and inhibited MAOA activity. Reduced the metabolism of epinephrine, 5-HT. GA (5 mg kg(-1)) protected the DNA fragmentation of frontotemporal cortex from hypoxic effects. Gangetin alkaloids are beneficial in the management of neurodegenerative disorders particularly for Alzheimer’s disease.

Effect of Liraglutide on Corneal Kindling Epilepsy Induced Depression and Cognitive Impairment in Mice.

GLP-1 play important role in neuroprotection and GLP-1 receptor deficit mice showed decreased seizure threshold and increased cognitive impairment. Therefore, study was premeditated to investigate the effect of liraglutide (GLP-1 analogue) on cornel kindling epilepsy induced co-morbidities in mice. Corneal kindling was induced by electrical stimulation (6mA, 50Hz, 3s); twice daily for 13days. Liraglutide (75 and 150µg/kg) and phenytoin (20mg/kg) were administered in corneal kindled groups. On day 14, elevated plus maze, passive shock avoidance paradigms were performed, and on day 15, retention was taken. On day 16 tail suspension test were performed. On 20th day challenge test was performed with same electrical stimulation and retention was observed on elevated plus maze and passive avoidance paradigm. Animal were sacrificed on 21st day for biochemical (LPO, GSH, and nitrite) and neurochemical (GABA, glutamate, DA, NE, 5-HT and their metabolites) estimation. Electrical stimulation by corneal electrode for 13days developed generalized clonic seizures, increased cognitive impairment, oxidative stress and neurochemical alteration in mice brain. Co-treatment with liraglutide (75 and 150μg/kg) significantly prevented the seizure severity, restored behavioural activity, oxidative stress and restored the altered level of neurotransmitters observed in corneal kindled mouse.

Neurochemical modulation involved in the beneficial effect of liraglutide, GLP-1 agonist on PTZ kindling epilepsy-induced comorbidities in mice

Epilepsy is a neurological disorder which occurs due to excessive firing of excitatory neurons in specific region of brain and associated with cognitive impairment and depression. GLP-1 has been reported to maintain hyperexcitability of neurons. Therefore, this study was designed to investigate the neuroprotective effect of liraglutide, GLP-1 analogue in PTZ kindling epilepsy-induced comorbidities and neurochemical alteration in mice. Male albino mice were administered PTZ (35mg/kg) on every alternate day up to 29th days and challenge test was performed on 33rd day. From 1st day liraglutide (75 and 150µg/kg) and diazepam (3mg/kg) were administered up to 33rd day, 30min prior to PTZ treatment. On 30th day animals were trained on elevated plus maze and passive shock avoidance paradigm and retention was recorded on 31st and 33rd day. On 32nd day tail suspension test was performed. Animals were sacrificed on 34th day for biochemical (LPO, GSH, and nitrite) and neurotransmitters (GABA, glutamate, DA, NE, 5-HT and their metabolites) estimation. Chronic treatment with PTZ developed generalized tonic-clonic seizures, reduced cognitive skills, increased oxidative stress and alteration in the level of neurotransmitters. Pre-treatment with liraglutide (75 and 150μg/kg) significantly prevented the seizure severity, restored behavioural activity, oxidative defence enzymes, and altered level of neurochemicals in mice brain. The protective effect of liraglutide is attributed to restoration of altered level of GABA, glutamate, DA, NE, and 5-HT by the up-regulation of GLP-1Rs in mice brain.

Pharmacological validation of in-silico guided novel nootropic potential of Achyranthes aspera L.

Ethnopharmacological relevanceAchyranthes aspera (A. aspera) has been used as a brain tonic in folk medicine. Although, ethnic use of medicinal plant has been basis for drug discovery from medicinal plants, but the available in-silico tools can be useful to find novel pharmacological uses of medicinal plants beyond their ethnic use. Aim of the studyTo validate in-silico prediction for novel nootropic effect of A. aspera by employing battery of tests in mice. Material and methodsPhytoconstituents of A. aspera reported in Dictionary of Natural Product were subjected to in-silico prediction using PASS and Pharmaexpert. The nootropic activity predicted for A. aspera was assessed using radial arm maze, passive shock avoidance and novel object recognition tests in mice. After behavioral evaluation animals were decapitated and their brains were collected and stored for estimation of glutamate levels and acetylcholinesterase activity. ResultsIn-silico activity spectrum for majority of A. aspera phytoconstituents exhibited excellent prediction score for nootropic activity of this plant. A. aspera extract treatment significantly improved the learning and memory as evident by decreased working memory errors, reference memory errors and latency time in radial arm maze, step through latency in passive shock avoidance and increased recognition index in novel object recognition were observed, moreover significantly enhanced glutamate levels and reduced acetylcholinesterase activity in hippocampus and cortex were observed as compared to the saline treated group. ConclusionIn-silico and in-vivo results suggest that A. aspera plant may improve the learning and memory by modulating the brain glutamatergic and cholinergic neurotransmission.

Protective effect on phenytoin-induced cognition deficit in pentylenetetrazol kindled mice: A repertoire of Glycyrrhiza glabra flavonoid antioxidants

Context: Glycyrrhiza glabra L. (Febaceae) has been widely used in traditional medicine and scientifically explored for its anticonvulsant and memory improving potential.Objective: The objective of this study is to investigate the effect of flavonoid rich fraction of G. glabra root extract against phenytoin-induced cognition deficit in pentylenetetrazol (PTZ) kindled mice.Materials and methods: The ethyl acetate fraction was initially screened in different in vitro free radical scavenging assays. For in vivo studies, the kindled mice in different groups were given 15 d post-treatment with phenytoin (25 mg/kg; p.o.) per se or in combination with varying doses of the fraction (5, 10, and 15 mg/kg; p.o.). Seizure severity score and cognitive functions were accessed using Racine's scale and passive shock avoidance paradigm, respectively on every 5th d after a PTZ challenge dose (35 mg/kg; i.p.). At the end of study, the animals were scarified for cerebral biochemistry.Results: The fraction showed marked antioxidant activity indicated by low IC50 values in DPPH (20.9 µg/mL), nitric oxide radical scavenging (195.2 µg/mL), and capacity of hydrogen peroxide scavenging (3.4 µg/mL) assays. Treatment with phenytoin per se and along with the flavonoid rich fraction showed significant reduction in seizure severity score as compared to vehicle control. The combined-treated groups also showed improved cognitive functions indicated by reduced number of mistakes and increased step-down latency in passive shock avoidance paradigm.Conclusion: From the results, it can be concluded that the flavonoid rich fraction in combination with phenytoin reduces seizure severity and improve cognitive functions in PTZ-kindled mice.