Effect of grewia hirsuta vahl ethanolic root extract on cognition in scopolamine induced amnesia

Objective Alzheimer's illnesses are becoming medical nightmares because there is no exact solution and existing nootropic medicines (Piracetam, tacrine, and metrifonate) have significant drawbacks. The goal of this study was to see if the ethanolic root extract of Grewia hirsuta (ERGH) could improve memory in rats who had been given scopolamine. Materials and procedures At rats, ERGH was given orally in dosages of 200 and 400 mg/kg for 28 days, followed by Scopolamine (18 mg/kg i.p.) from the 25th to the 27th day. The usual nootropic drug was piracetam (200 mg/kg). The elevated plus maze (EPM), Morris water maze (MWM), and passive avoidance (PA) paradigms are used to assess cognitive functioning. Invivo anti-oxidant activity and brain acetylcholine esterase (AchE) activity were assessed. Results: At the indicated doses, ERGH extract showed a substantial memory-enhancing activity by decreasing the transfer latency in EPM, increasing the escape latency in MWM, and increasing the shock-free zone in PA. In scopolamine-induced amnesia rats, pretreatment with ERGH resulted in a significant drop in AchE enzyme, an increase in enzymatic antioxidant, and a decrease in MDA levels. Conclusion Because of its several favorable benefits, such as memory-improving properties, anticholinesterase activity, and antioxidant activity, ERGH may prove to be a useful drug in the current study, and it would be important to investigate its potential in the care of Alzheimer's patients.

The effects of galangin in prepulse inhibition test and experimental schizophrenia models

Objective: Acetylcholinesterase inhibitors are the focus of interest in the management of schizophrenia. We aimed to investigate the effects of acute galangin administration, a flavonoid compound with acetylcholinesterase inhibiting activity, on schizophrenia-associated cognitive deficits in rats and schizophrenia models in mice. Methods: Apomorphine-induced prepulse inhibition (PPI) disruption for cognitive functions, nicotinic, muscarinic and serotonergic mechanism involvement, and brain acetylcholine levels were investigated in Wistar rats. Apomorphine-induced climbing, MK-801-induced hyperlocomotion, and catalepsy tests were used as schizophrenia models in Swiss albino mice. The effects of galangin were compared with acetylcholinesterase inhibitor donepezil, and typical and atypical antipsychotics haloperidol and olanzapine, respectively. Results: Galangin (50,100 mg/kg) enhanced apomorphine-induced PPI disruption similar to donepezil, haloperidol, and olanzapine (p<0.05). This effect was not altered in the combination of galangin with the nicotinic receptor antagonist mecamylamine (1 mg/kg), the muscarinic receptor antagonist scopolamine (0.05 mg/kg), or the serotonin-1A receptor antagonist WAY-100635 (1 mg/kg) (p>0.05). Galangin (50,100 mg/kg) alone increased brain acetylcholine concentrations(p<0.05), but not in apomorphine-injected rats (p>0.05). Galangin (50 mg/kg) decreased apomorphine-induced climbing and MK-801-induced hyperlocomotion similar to haloperidol and olanzapine (p<0.05), but did not induce catalepsy, unlike them. Conclusion: We suggest that galangin may help enhance schizophrenia-associated cognitive deficits, and nicotinic, muscarinic cholinergic and serotonin-1A receptors are not involved in this effect. Galangin also exerted an antipsychotic-like effect without inducing catalepsy and may be considered as an advantageous antipsychotic agent.

Cholinergic Modulation of the Immune System in Neuroinflammatory Diseases

Frequent diseases of the CNS, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and psychiatric disorders (e.g., schizophrenia), elicit a neuroinflammatory response that contributes to the neurodegenerative disease process itself. The immune and nervous systems use the same mediators, receptors, and cells to regulate the immune and nervous systems as well as neuro-immune interactions. In various neurodegenerative diseases, peripheral inflammatory mediators and infiltrating immune cells from the periphery cause exacerbation to current injury in the brain. Acetylcholine (ACh) plays a crucial role in the peripheral and central nervous systems, in fact, other than cells of the CNS, the peripheral immune cells also possess a cholinergic system. The findings on peripheral cholinergic signaling, and the activation of the “cholinergic anti-inflammatory pathway” mediated by ACh binding to α7 nAChR as one of the possible mechanisms for controlling inflammation, have restarted interest in cholinergic-mediated pathological processes and in the new potential therapeutic target for neuro-inflammatory-degenerative diseases. Herein, we focus on recent progress in the modulatory mechanisms of the cholinergic anti-inflammatory pathway in neuroinflammatory diseases.

Amyloid Beta

Alzheimer's disease (AD), exhibiting accumulation of amyloid beta (Aβ) peptide as a foremost protagonist, is one of the top five causes of deaths. It is a neurodegenerative disorder (ND) that causes a progressive decline in memory and cognitive abilities. It is characterized by deposition of Aβ plaques and neurofibrillary tangles (NFTs) in the neurons, which in turn causes a decline in the brain acetylcholine levels. Aβ hypothesis is the most accepted hypothesis pertaining to the pathogenesis of AD. Amyloid Precursor Protein (APP) is constitutively present in brain and it is cleaved by three proteolytic enzymes (i.e., alpha, beta, and gamma secretases). Beta and gamma secretases cleave APP to form Aβ. Ubiquitin Proteasome System (UPS) is involved in the clearing of Aβ plaques. AD also involves impairment in UPS. The novel disease-modifying approaches involve inhibition of beta and gamma secretases. A number of clinical trials are going on worldwide with moieties targeting beta and gamma secretases. This chapter deals with an overview of APP and its enzymatic cleavage leading to AD.

Cholinesterase Inhibitors for Alzheimer's Disease: Multitargeting Strategy Based on Anti-Alzheimer's Drugs Repositioning

: In the brain, acetylcholine (ACh) is regarded as one of the major neurotransmitters. During the advancement of Alzheimer's disease (AD) cholinergic deficits occur and this can lead to extensive cognitive dysfunction and decline. Acetylcholinesterase (AChE) remains a highly feasible target for the symptomatic improvement of AD. Acetylcholinesterase (AChE) remains a highly viable target for the symptomatic improvement in AD because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AChE for myasthenia gravis had effectively proven that AChE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEIs) have been continued to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs which are under development and their respective mechanisms of actions.

Amyloid Beta

Alzheimer's disease (AD), exhibiting accumulation of amyloid beta (Aβ) peptide as a foremost protagonist, is one of the top five causes of deaths. It is a neurodegenerative disorder (ND) that causes a progressive decline in memory and cognitive abilities. It is characterized by deposition of Aβ plaques and neurofibrillary tangles (NFTs) in the neurons, which in turn causes a decline in the brain acetylcholine levels. Aβ hypothesis is the most accepted hypothesis pertaining to the pathogenesis of AD. Amyloid Precursor Protein (APP) is constitutively present in brain and it is cleaved by three proteolytic enzymes (i.e., alpha, beta, and gamma secretases). Beta and gamma secretases cleave APP to form Aβ. Ubiquitin Proteasome System (UPS) is involved in the clearing of Aβ plaques. AD also involves impairment in UPS. The novel disease-modifying approaches involve inhibition of beta and gamma secretases. A number of clinical trials are going on worldwide with moieties targeting beta and gamma secretases. This chapter deals with an overview of APP and its enzymatic cleavage leading to AD.

ENHANCING COGNITIVE FUNCTION OF HEALTHY WISTAR RATS WITH AQUEOUS EXTRACT OF Centella asiatica

Background: Centella asiatica (L.) Urb is a native herb from Asian countries such as India, China, and Indonesia. This herb has been widely used as a cure for various diseases. However, studies investigating the aqueous extract of Centella asiatica as a nootropic in healthy individuals are still very limited.Objective: This study aims to investigate the potential of aqueous extract of Centella asiatica in enhancing cognitive function of healthy male Wistar rats.Methods: Rats were randomly allocated to four treatment groups, i.e. without treatment and aqueous Centella asiatica extract at doses of 200, 400 and 800 mg/kg. To determine enhancement of cognitive function, novel object recognition (NOR) test was conducted after the course of treatment. Acetylcholine content was assessed by enzyme-linked immunosorbent assay.Results: There was a significantly high preference index towards the novel object in the NOR test in groups treated with 200 mg/kg and 800 mg/kg of the aqueous extract compared to control. This was further confirmed by a significant increase of brain acetylcholine content in rats treated with 200 mg/kg of the extract.Conclusion: Therefore, this study confirms that the aqueous extract is effective in enhancing cognitive performance of healthy Wistar rats.

EVALUATION OF LEARNING AND MEMORY ENHANCING ACTIVITY OF COCCINIA GRANDIS FRUITS IN RATS

Objectives: To assess the learning and memory enhancing activity of the Coccinia grandis fruits in rats using Elevated plus maze (EPM), Hebb-William maze (HWM) and Morris water maze (MWM ) and to evaluate brain Acetylcholine esterase activity, lipid peroxidation, Superoxide dismutase, Catalase, Glutathione. Materials and methods: Wistar rats (100-150 gm) of either sex, were divided into 5 groups (n=6). Group-I (control) animals received vehicle, Group-II animals received diazepam(1 mg/kg i.p), Groups III ,IV and V animals received Coccinia grandis- 500 mg/kg p.o, 1000 mg/kg p.o and Piracetam (400 mg/kg i.p) respectively for 27 days, followed by diazepam (1 mg/kg i.p) single dose on 19th and 27th day. Assessment of transfer latency (TL), time taken to reach reward chamber (TRC) and swim latency (SL) was done on 16th, 17th, 18th, 19th and 27th day using EPM, HWM and MWM respectively. Rats were sacrificed on 28th day, brain acetylcholine esterase activity, lipid peroxidation, superoxide dismutase, glutathione and catalase levels were estimated. The data was analyzed by one way ANOVA followed by Dunnett’s test. P ≤ 0.05 was considered significant. Result: Coccinia grandis decreased TL, TRC and SL in comparison to diazepam treated rats, decreased acetylcholine esterase activity and lipid peroxidation, and increased superoxide dismutase, glutathione and catalase in brain. Conclusion: The Coccinia grandis enhanced learning and memory activity. This nootropic effect can be attributed to their antioxidant and neuroprotective property. Keywords: Memory, EPM, HWM, MWM, Piracetam, Diazepam.

BIOACTIVITY-GUIDED ISOLATION OF MEMORY-ENHANCING COMPOUND FROM CHLOROFORM EXTRACT OF ROOTS OF PLUMBAGO ZEYLANICA LINN.

Aim: The main aim of our study is to isolate the active compound from roots of Plumbago zeylanica Linn. by bioactivity-guided isolation and evaluate its memory-enhancing effect by Morris water maze.Methods: Roots were extracted by successive solvent methods by petroleum ether, chloroform, methanol, butanol, and finally, water. Chloroform extract was selected for isolation, and plumbagin was isolated by hexane and ethyl acetate as solvent system. Plumbagin was evaluated by Morris water test, and brain acetylcholine esterase level was measured.Result: Plumbagin showed a significant decrease of escape latency and increase of time spent in target quadrant by mice in Morris water maze indicating improvement of learning and memory. It also significantly decreases the cholinesterase level in the brain.Conclusion: Learning and memory of mice doubtless may be through embarrassment of brain acetyl cholinesterase activity and through involvement of GABA-benzodiazepine pathway. Further detailed study is required to explore the other possible mechanisms for the management of cognitive disorders.