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Neuroprotective Effects of Meloxicam and Selegiline in Scopolamine-Induced Cognitive Impairment and Oxidative Stress  [PDF]
Puchchakayala Goverdhan,Akina Sravanthi,Thati Mamatha
International Journal of Alzheimer's Disease , 2012, DOI: 10.1155/2012/974013
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a gradual decline in memory associated with shrinkage of brain tissue, with localized loss of neurons mainly in the hippocampus and basal forebrain, with diminished level of central cholinergic neurotransmitter-acetylcholine and also reported to be associated with accumulation of ubiquitinated proteins in neuronal inclusions and also with signs of inflammation. In these disorders, the abnormal protein aggregates may themselves trigger the expression of inflammatory mediators, such as cyclooxygenase 2 (COX-2). In the present study, the effects of Meloxicam, Selegiline, and coadministration of these drugs on scopolamine-induced learning and memory impairments in mice were investigated. Rectangular maze test, Morris water maze test, Locomotor activity, and Pole climbing test were conducted to evaluate the learning and memory parameters. Various biochemical parameters such as acetylcholinesterase(AChE), TBARS assay, catalase activity, and DPPH assay were also assessed. The present study demonstrates that Meloxicam, Selegiline, and co-administration of these test drugs had potential therapeutic effects on improving the antiamnesic activity in mice through inhibiting lipid peroxidation, augmenting endogenous antioxidant enzymes, and decreasing acetylcholinesterase activity in brain. The memory enhancing capacity of the drugs was very significant when compared to disease control ( ). 1. Introduction Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder that is slow in onset but leads to dementia, unusual behavior, personality changes, and ultimately death [1]. AD is characterized by the presence of excessive amounts of neuritic plaques containing amyloid β protein and abnormal tau protein filaments in the form of neurofibrillary tangles. Loss of cholinergic cells, particularly in the basal forebrain, is accompanied by loss of the neurotransmitter acetylcholine [2]. A decrease in acetyl choline in the brain of patients with AD appears to be a critical element in producing dementia [3]. AChE inhibitors from general chemical classes such as physostigmine, tacrine, galantamine, and heptylphysostigmine have been tested for the symptomatic treatment of AD [4]. However, nonselectivity of these drugs, their limited efficacy, poor bioavailability, adverse cholinergic side effects in the periphery, narrow therapeutic ranges, and hepatotoxicity are among the several limitations to their therapeutic success [5]. Therefore, it is worthwhile to explore the utility of
Neuroprotective Effect of Phyllanthus acidus L. on Learning and Memory Impairment in Scopolamine-Induced Animal Model of Dementia and Oxidative Stress: Natural Wonder for Regulating the Development and Progression of Alzheimer’s Disease  [PDF]
Md. Sahab Uddin, Abdullah Al Mamun, Md. Saddam Hossain, Muhammad Ashaduzzaman, Md. Ali Asif Noor, Md. Sarwar Hossain, Md. Josim Uddin, Jyotirmoy Sarker, Md. Asaduzzaman
Advances in Alzheimer's Disease (AAD) , 2016, DOI: 10.4236/aad.2016.52005
Abstract: Nature is the best source of complementary and alternative medicine. The plant Phyllanthus acidus (PA) L. has been used traditionally in pain, inflammatory and oxidative stress related disorders. In this consequence, methanolic extract of PA (MEPA) was selected to explore the ability of this plant to enhance cognitive function, brain antioxidant enzymes and anti-acetylcholinesterase activity which can be used for the treatment of oxidative stress related disorders like Alzheimer’s disease (AD). The purpose of this study was to investigate the neuroprotective effect of MEPA on learning and memory impairment in scopolamine-induced rats of dementia and oxidative stress. Treatment with MEPA (i.e., 100 and 200 mg/kg b.w.) was investigated in scopolamine-treated Swiss albino male rats for 14 days and its neuroprotective effects were examined using Elevated Plus Maze (EPM) test, Passive Avoidance (PA) test, Novel Object Recognition (NOR) test, Morris Water Maze (MWM) test as well as level of antioxidant enzymes such as catalase (CAT), super oxide dismutase (SOD), glutathione reductase (GSR), glutathione-S-transferase (GST), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), lipid peroxidation (TBARS) contents and acetylcholinesterase (AChE) activity in rat brain tissue homogenates. Administration of MEPA significantly (P < 0.05, P < 0.01; P < 0.01) decreased RTL (retention transfer latency) in rats on 7th and 14th day compared to the disease control and control group in the EPM test. In PA test the doses of MEPA suggestively (P < 0.05, P < 0.001; P < 0.05, P < 0.01) increased STL (step-through latency) in rats on 7th and 14th day with respect to disease control and control group. For NOR test administration of MEPA considerably (P < 0.01, P < 0.001; P < 0.01) increased the DI (discrimination index) in rats with respect to that of disease control and control group. The doses of MEPA markedly (P < 0.05, P < 0.01; P < 0.01) decreased EL (escape latency) and significantly (P < 0.01, P < 0.001; P < 0.05, P < 0.01) increased TSTQ (time spent in the target quadrant) on successive days as compared to that of disease control and control group in the acquisition trial of MWM test. In case of probe trial of MWM test MEPA administration considerably (P < 0.01; P < 0.05, P < 0.01) increased TSTQ and significantly (P < 0.05, P < 0.01; P < 0.05, P < 0.01) increased TSA (time spent in the annuli) in rats on successive days as compared to that
Evaluation of Antihyperlipidemic, Hypoglycemic and Antioxidant Potential of Ficus infectoria Methanolic Extract in Wistar Rats  [PDF]
Ashok Kumar Gupta,Subhash Dwivedi,Aseem Sharma,Gajraj Singh Lodhi
Journal of Pharmacognosy and Phytochemistry , 2013,
Abstract: Objective- To explore the hypolipidemic, hypoglycemic and antioxidant activity of the methanolic extract of Ficus infectoria on fructose induced hyperlipidemia and hyperglycemia in Wistar rats.Materials and Methods- Hyperlipidemia and hypoglycemia in rats were induced by fructose solution (10% w/v, p.o., ad libitum) for 3rd and 8th weeks respectively. These activities were measured by estimating the triglyceride, total cholesterol, LDL, VLDL, HDL and serum glucose levels. Hydrogen peroxide (H2O2) assay method was used to determine the antioxidant activity.Results- In all model, F. infectoria at 200mg/kg and 400mg/kg showed significant effect. Fructose feeding increased serum biochemical parameters like triglyceride, total cholesterol, LDL, VLDL and serum glucose levels while decreases the HDL level. In fructose fed rats, F. infectoria at 200 mg/kg and 400 mg/kg significantly prevented the increase in serum biochemical parameters while decrease in HDL level. Also it was able to scavenge the free radical generated by Hydrogen peroxide (H2O2).Conclusion- The present study indicates that methanolic extract of F. infectoria leaf and bark (mixture) has Antihyperlipidemic, hypoglycemic and antioxidant potentials. In future it may be useful in the management of insulin resistant.
Bacopa monniera Attenuates Scopolamine-Induced Impairment of Spatial Memory in Mice
Manish Kumar Saraf,Sudesh Prabhakar,Krishan Lal Khanduja,Akshay Anand
Evidence-Based Complementary and Alternative Medicine , 2011, DOI: 10.1093/ecam/neq038
Abstract: Scopolamine, an anticholinergic, is an attractive amnesic agent for discerning the action of candidate antiamnesic drugs. Bacopa monniera Linn (Syn. Brahmi) is one such antiamnesic agent that is frequently used in the ancient Indian medical system. We have earlier reported the reversal of diazepam-induced amnesia with B. monniera. In this study we wanted to test if scopolamine-induced impairment of spatial memory can also be ameliorated by B. monniera using water maze mouse model. The objective of study was to study the effect of B. monniera on scopolamine-induced amnesia. We employed Morris water maze scale to test the amnesic effect of scopolamine and its reversal by B. monniera. Rotarod test was conducted to screen muscle coordination activity of mice. Scopolamine significantly impaired the acquisition and retrieval of memory producing both anterograde and retrograde amnesia. Bacopa monniera extract was able to reverse both anterograde and retrograde amnesia. We propose that B. monniera’s effects on cholinergic system may be helpful for developing alternative therapeutic approaches for the treatment of Alzheimer’s disease.
The role of CA1 α-adrenoceptor on scopolamine induced memory impairment in male rats  [cached]
Nasrin-Sadat Azami,morteza piri,Mehrdad Jahanshahi,Shahrbanoo oryan
Physiology and Pharmacology , 2010,
Abstract: Introduction: Similarities in the memory impairment between Alzheimer patients and scopolamine treated animals have been reported. In the present study, the possible role of α-adrenergic receptors of the dorsal hippocampus on scopolamine state-dependent memory in adult male Wistar rats was evaluated. Methods: The animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-through type inhibitory avoidance task, and tested 24 h after training to measure stepthrough latency. Results: Post-training intra-CA1 administration of scopolamine (0.5 and 2μg/rat) dose-dependently reduced the step-through latency, showing an amnestic response. Amnesia produced by post-training scopolamine (2 μg/rat) was reversed by pre-test administration of the scopolamine (0.5 and 2 μg/rat) that is due to a state-dependent effect. Pre-test intra-CA1 injection of α1-adrenoceptor agonist, phenylephrine (0.25, 0.5 μg/rat) in the dose range that we used, could not affect memory impairment induced by post-training injection of scopolamine (2 μg/rat). However intra-CA1 pretest injection of α2-adrenoceptor agonist, clonidine (0.5 μg/rat) improved post-training scopolamine (2 μg/rat) intra- CA1 injection induced retrieval impairment. Furthermore, pre-test intra-CA1 microinjection of phenylephrine (0.25 and 0.5 μg/rat) or clonidine (0.25 and 0.5 μg/rat) with an ineffective dose of scopolamine (0.25 μg/rat), synergistically improved memory performance impaired by post-training scopolamine (2 μg/rat). Our results also showed that, pre-test injection of α1-receptor antagonist prazosin (1, 2 μg/rat) or α2-receptors antagonist yohimbine (1, 2 μg/rat) before effective dose of scopolamine (2 μg/rat) prevented the improvement of memory by pre-test scopolamine. Conclusion: These results suggest that α1- and α2-adrenergic receptors of the dorsal hippocampal CA1 region may play an important role in scopolamine-induced amnesia and scopolamine state-dependent memory.
Phytoceramide Shows Neuroprotection and Ameliorates Scopolamine-Induced Memory Impairment  [PDF]
Jae-Chul Jung,Yeonju Lee,Sohyeon Moon,Jong Hoon Ryu,Seikwan Oh
Molecules , 2011, DOI: 10.3390/molecules16119090
Abstract: The function and the role phytoceramide (PCER) and phytosphingosine (PSO) in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS) showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o.) recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.
Neuroprotective Effects of Centella asiatica against Intracerebroventricular Colchicine-Induced Cognitive Impairment and Oxidative Stress  [PDF]
Anil Kumar,Samrita Dogra,Atish Prakash
International Journal of Alzheimer's Disease , 2009, DOI: 10.4061/2009/972178
Abstract: Oxidative stress appears to be an early event involved in the pathogenesis of Alzheimer's disease. The present study was designed to investigate the neuroprotective effects of Centella asiatica against colchicine-induced memory impairment and oxidative damage in rats. Colchicine (15 g/5 L) was administered intracerebroventricularly in the lateral ventricle of male wistar rats. Morris water maze and plus-maze performance tests were used to assess memory performance tasks. Various biochemical parameters such as lipid peroxidation, nitrite, reduced glutathione, glutathione-S-transferase, superoxide dismutase, acetylcholinesterase were also assessed. ICV colchicine resulted marked memory impairment and oxidative damage. Chronic treatment with Centella asiatica extract (150 and 300 mg/kg, p.o.) for a period of 25 days, beginning 4 days prior to colchicine administration, significantly attenuated colchicine-induced memory impairment and oxidative damage. Besides, Centella asiatica significantly reversed colchicines administered increase in acetylcholinesterase activity. Thus, present study indicates protective effect of Centella asiatica against colchicine-induced cognitive impairment and associated oxidative damage.
Protective Effects of Mangosteen Extract on H2O2-Induced Cytotoxicity in SK-N-SH Cells and Scopolamine-Induced Memory Impairment in Mice  [PDF]
Jintana Sattayasai, Pongsatorn Chaonapan, Tarinee Arkaravichie, Rungtip Soi-ampornkul, Sarawut Junnu, Patcharakajee Charoensilp, Jutima Samer, Jiraporn Jantaravinid, Patarabutr Masaratana, Bhoom Suktitipat, Juthatip Manissorn, Visith Thongboonkerd, Neelobol Neungton, Primchanien Moongkarndi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0085053
Abstract: Mangosteen extracts (ME) contain high levels of polyphenolic compounds and antioxidant activity. Protective effects of ME against β-amyloid peptide (Aβ), induced cytotoxicity have been reported. Here, we further studied the protective effects of ME against oxidative stress induced by hydrogen peroxide (H2O2) and polychlorinated biphenyls (PCBs), and demonstrated the protection against memory impairment in mice. The cytoprotective effects of ME were measured as cell viability and the reduction in ROS activity. In SK-N-SH cell cultures, 200 μg/ml ME could partially antagonize the effects of 150 or 300 μM H2O2 on cell viability, ROS level and caspase-3 activity. At 200, 400 or 800 μg/ml, ME reduced AChE activity of SK-N-SH cells to about 60% of the control. In vivo study, Morris water maze and passive avoidance tests were used to assess the memory of the animals. ME, especially at 100 mg/kg body weight, could improve the animal’s memory and also antagonize the effect of scopolamine on memory. The increase in ROS level and caspase-3 activity in the brain of scopolamine-treated mice were antagonized by the ME treatment. The study demonstrated cytoprotective effects of ME against H2O2 and PCB-52 toxicity and having AChE inhibitory effect in cell culture. ME treatment in mice could attenuate scopolamine-induced memory deficit and oxidative stress in brain.
The Neuroprotective Effect of Methanol Extract of Gagamjungjihwan and Fructus Euodiae on Ischemia-Induced Neuronal and Cognitive Impairment in the Rat
Bombi Lee,Eu-Jung Choi,Eun-Jung Lee,Seung-Moo Han,Dae-Hyun Hahm,Hye-Jung Lee,Insop Shim
Evidence-Based Complementary and Alternative Medicine , 2011, DOI: 10.1093/ecam/nep028
Abstract: Gagamjungjihwan (GJ), a decoction consisting of five herbs including ginseng, Acori Graminei Rhizoma, Uncariae Ramulus et Uncus, Polygalae Radic and Frustus Euodiae (FE), has been widely used as herbal treatment for ischemia. In order to investigate the neuroprotective action of this novel prescription, we examined the influence of GJ and FE on learning and memory using the Morris water maze and studied their affects on the central cholinergic system in the hippocampus with neuronal and cognitive impairment. After middle cerebral artery occlusion was applied for 2 h, rats were administered GJ (200 mg kg−1, p.o.) or FE (200 mg kg−1, p.o.) daily for 2 weeks, followed by training and performance of the Morris water maze tasks. Rats with ischemic insults showed impaired learning and memory of the tasks. Pre-treatment with GJ and FE produced improvement in the escape latency to find the platform. Pre-treatments with GJ and FE also reduced the loss of cholinergic immunoreactivity in the hippocampus. The results demonstrated that GJ and FE have a protective effect against ischemia-induced neuronal and cognitive impairment. Our results suggest that GJ and FE might be useful in the treatment of vascular dementia.
Antiamnesic effect of stevioside in scopolamine-treated rats  [cached]
Sharma Deepika,Puri Munish,Tiwary Ashok,Singh Nirmal
Indian Journal of Pharmacology , 2010,
Abstract: The present study was undertaken to explore the potential of stevioside in memory dysfunction of rats. Memory impairment was produced by scopolamine (0.5 mg/kg, i.p.) in animals. Morris water maze (MWM) test was employed to assess learning and memory. Brain acetylcholinestrase enzyme (AChE) activity was measured to assess the central cholinergic activity. The levels of brain thiobarbituric acid-reactive species (TBARS) and reduced glutathione (GSH) were estimated to assess the degree of oxidative stress. Scopolamine administration induced significant impairment of learning and memory in rats, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Pretreatment of stevioside (250 mg/kg dose orally) significantly reversed scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and brain oxidative stress levels. It may be concluded that stevioside exerts a memory-preservative effect in cognitive deficits of rats possibly through its multiple actions.
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