Emilia coccinae (SIMS) G Extract improves memory impairment, cholinergic dysfunction, and oxidative stress damage in scopolamine-treated rats.
ABSTRACT: BACKGROUND:E. coccinae (SIMS) G. (Asteraceae) is an annual plant commonly found throughout the plain of the Central Africa and widely used in Cameroonian folk medicine for the treatment of fever and convulsions in children. We previously reported that the methanolic extract of this plant improved spatial memory. However no underlying mechanism was explored. The present study was undertaken to investigate the effects of the hydroalcoholic extract of Emilia coccinae on memory in scopolamine treated rats and to propose possible mechanisms of action. METHODS:Novel object recognition and Y-maze paradigm were used to test memory while oxidative profile, AChE and ACh level of the whole brain were assessed to outline the mechanism of nootropic activity of the extract. 200 and 400 mg/kg of the extract were chronically administrated during 14 consecutive days in separate groups of scopolamine intraperitoneal treated rats (1.5 mg/kg). RESULTS:The hydroalcoholic extract of Emilia coccinae (HEEC) at the dose of 200 mg/kg significantly improved the memory of rats and reversed the amnesia induced by scopolamine. In addition, we showed that this extract is decreasing the acetyl cholinesterase activity while also increasing the acetylcholine levels in the brain. HEEC (200 and 400 mg/kg) significantly increased antioxidant enzyme activities (SOD, GSH and CAT) and reduced lipid peroxidation (MDA level) in the rat whole brain homogenates. CONCLUSIONS:Taken together, our results suggested that the hydroalcoholic extract of Emilia coccinae ameliorated the cognitive dysfunction in scopolamine treated rats through the blockage of the oxidative effect of scopolamine and inhibition of AChE activity.
Project description:<h4>Background</h4>Trichilia catigua A. Juss. (Meliaceae) is a species known as catuaba and used in folk medicine for the treatment of fatigue, stress, impotence and memory deficit. The main phytochemical compounds identified in the barks of T. catigua are flavalignans, flavan-3-ols and flavonoids which are associated with its antioxidant activity. Pre-clinical studies with T. catigua extracts have identified many pharmacological properties, such as anti-inflammatory, antidepressant, antinociceptive, pro-memory and neuroprotective against ischemia and oxidative stress. This study was designed in order to compare the chemical composition and in vitro antioxidant and anticholinesterase activity of four different polarity extracts and selected the one most active for in vivo studies in rodent models of stress, fatigue and memory.<h4>Methods</h4>Hexane, chloroform, hydroalcoholic and aqueous extracts from bark of Trichilia catigua were analyzed by RPHPLC-DAD-ESI-MS/MS. Antioxidant activity was assessed by 2,2-diphenyl-1-picryl hydrazyl (DPPH) assay and acetylcholinesterase inhibition by Ellman's modified method. In vivo studies (stress, fatigue and memory) were carried out with adult male mice and rats treated with hydroalcoholic extract in doses of 25-300 mg/kg (p.o.).<h4>Results</h4>We confirmed the presence of cinchonain IIa, Ia and Ib, as main constituents in the four extracts, while procyanidins were detected only in hydroalcoholic extract. Antioxidant and anticholinesterase activity were observed for all extracts, with most potent activity found on the hydroalcoholic extract (EC<sub>50</sub> =?43 ?g/mL and IC<sub>50</sub> =?142 ?g/mL for DPPH scavenger and acetylcholinesterase inhibition, respectively). The treatment of laboratory animals with hydroalcoholic extract did not protect rats from cold immobilization stress and did not prevent the scopolamine-induced amnesia in mice. However, the treatment of mice with the hydroalcoholic extract partially reduced the fatigue induced by treadmill, since the highest dose increased the spontaneous locomotor activity and reduced the deficit on grip strength after the forced exercise (p <?0.05), in some observation times.<h4>Conclusions</h4>These data suggest the hydroalcoholic extract as the most suitable for plant extraction and partially support the folk use of T. catigua as antifatigue drug. . Trichilia catigua hydroalcoholic extract exhibits antioxidant and anticholinesterase activity in vitro and reduces the fatigue induced by forced exercise.
Project description:Acetylcholinesterase (AChE) inhibitors represent a major class of drugs which provide symptomatic relief and improvement in cognitive function in Alzheimer's disease (AD). In this study, cubebin, a dibenzylbutyrolactone lignan, was isolated from Piper cubeba and investigated for its AChE inhibitory activity in an attempt to explore its potential for memory-enhancing activities in mice.Molecular docking of cubebin was carried out followed by in vitro AChE activity. Mice were treated with cubebin (25 & 50 mg/kg; i.p.), for three days and memory impairment was induced by scopolamine (3 mg/kg; i.p.). Memory function was evaluated by Morris water maze (MWM) test. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain.Molecular docking study revealed that cubebin was well bound within the binding site of the AChE enzyme showing interactions such as π-π stacking and hydrogen bonding with residues present therein. Cubebin inhibited AChE enzyme in an in vitro assay with IC50value of 992 μM. Scopolamine administration caused a significant impairment of learning and memory in mice, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and oxidative stress in mice brain. Pre-treatment of cubebin (25 and 50 mg/kg; i.p.) significantly prevented scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and oxidative stress level.Cubebin showed promising protective activity in scopolamine-induced spatial memory impairment in mice. This could be attributed to its brain AChE inhibition and antioxidant activity.
Project description:The present work was undertaken to evaluate the ability of <i>F. umbellata</i> aqueous extract and its major component 7-methoxycoumarin (MC) to improve scopolamine-induced spatial memory impairment in ovariectomized Wistar rats. For this to be done, 10 sham-operated and 30 postmenopausal-like rats were randomly distributed in eight groups (<i>n</i> = 5) and treated with distilled water (2?mL/250?g), estradiol valerate (1?mg/kg BW), piracetam (1.5?mg/kg BW), <i>F. umbellata</i> aqueous extract (50 and 200?mg/kg BW), or MC (1?mg/kg BW) for 21 consecutive days. Before and after the memory impairment with scopolamine (2?mg/kg BW), animals underwent behavioral evaluations on Y- and radial mazes. As results, age and ovariectomy did not induce significant changes in the reference memory errors. While age decreased working memory errors, ovariectomy increased it. The MC as well as <i>F. umbellata</i> extract significantly increased (<i>p</i> < 0.01) the percentage of spontaneous alternation and decreased (<i>p</i> < 0.001) working and spatial reference memory errors and anxiety parameters (rearing and grooming) in ovariectomized rats. MC significantly reduced (<i>p</i> < 0.05) the MDA level, but resulted in an increase in GSH level in brain homogenates. These results suggest that MC is endowed with neuroprotective effects and could account for the neuroprotective effects of <i>F. umbellata</i> in rats.
Project description:Ziziphus mucronata Willd, also known as "buffalo thorn," belongs to the family Rhamnaceae. Its bark and leaves are used in folk medicine for the treatment of various deficiencies related to nociception, inflammation, mood, and depression. Still, there is a lack of scientific data regarding its potential effect on learning and memory process. The present study was designed to investigate the neuroprotective potential of Ziziphus mucronata (ZM) on learning and memory impairment in a scopolamine-induced model of dementia in mice. The phytochemical analysis revealed five cyclopeptide alkaloids (sanjoinines) in the extract from Ziziphus Mucronata leaves using LC-HRMS, and the structural characterization of these compounds was determined via MS/MS. Alzheimer-type amnesia was induced by an intraperitoneal injection of scopolamine (1?mg/kg) to mice for 7 consecutive days. ZM (150?mg/kg, 300?mg/kg, and 600?mg/kg) and piracetam (150?mg/kg) were orally administrated to mice daily for a period of 14 days. Memory-related behavioural parameters were evaluated using the radial arm maze task for 7 days, Y-maze, and novel object recognition task. At the end of protocol schedule, animals were sacrificed, and the levels of acetylcholinesterase, malondialdehyde, catalase, and superoxide dismutase were determined in brain homogenates. Histological studies of the hippocampus were subsequently performed. The long-term scopolamine-injected group decreased the spontaneous alternation (Y-maze), the discrimination index, and the time taken to explore the new object (novel object recognition task). These effects were significantly reversed by ZM at all the doses tested. In the radial arm maze task, ZM (300 and 600?mg/kg) significantly decreased the working and reference memory errors when compared with the demented group. Scopolamine-mediated changes in AChE activity were also attenuated by ZM in mice. In addition, extract-treated groups showed a significant increase in the level of CAT and SOD activity and decreased levels of MDA in the mice brains, as compared with the control group. The present study suggests that ZM could have an important role in neuroprotection on this scopolamine-induced model of Alzheimer-type dementia.
Project description:Terminalia chebula Retz. (Combretaceae) is a traditional herbal medicine that is widely used in the treatment of diabetes, immunodeficiency diseases, and stomach ulcer in Asia. However, the anti-amnesic effect of T. chebula has not yet been investigated. The present study was designed to determine whether T. chebula extract (TCE) alleviates amnesia induced by scopolamine in mice. We also investigated possible mechanisms associated with cholinergic system and anti-oxidant effects.TCE (100 or 200 mg/kg) was orally administered to mice for fourteen days (days 1-14), and scopolamine was intraperitoneally injected to induce memory impairment for seven days (days 8-14). Learning and memory status were evaluated using the Morris water maze. Hippocampal levels of acetylcholine (ACh), acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) were measured ex vivo. Levels of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) in the hippocampus were also examined.In the Morris water maze task, TCE treatment reversed scopolamine-induced learning and memory deficits in acquisition and retention. TCE reduced hippocampal AChE activities and increased ChAT and ACh levels in the scopolamine-induced model. Moreover, TCE treatment suppressed scopolamine-induced oxidative damage by ameliorating the increased levels of ROS, NO, and MDA.These findings suggest that TCE exerts potent anti-amnesic effects via cholinergic modulation and anti-oxidant activity, thus providing evidence for its potential as a cognitive enhancer for amnesia.
Project description:Deficiency of the cholinergic system is thought to play a vital role in cognitive impairment of dementia. DL0410 was discovered as a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinestease (BuChE), with potent efficiency in in-vitro experiments, but its in vivo effect on the cholinergic model has not been evaluated, and its action mechanism has also not been illustrated. In the present study, the capability of DL0410 in ameliorating the amnesia induced by scopolamine was investigated, and its effect on the cholinergic system in the hippocampus and its binding mode in the active site of AChE was also explored. Mice were administrated DL0410 (3 mg/kg, 10 mg/kg, and 30 mg/kg), and mice treated with donepezil were used as a positive control. The Morris water maze, escape learning task, and passive avoidance task were used as behavioral tests. The test results indicated that DL0410 could significantly improve the learning and memory impairments induced by scopolamine, with 10 mg/kg performing best. Further, DL0410 inhibited the AChE activity and increased acetylcholine (ACh) levels in a dose-dependent manner, and interacted with the active site of AChE in a similar manner as donepezil. However, no difference in the activity of BuChE was found in this study. All of the evidence indicated that its AChE inhibition is an important mechanism in the anti-amnesia effect. In conclusion, DL0410 could be an effective therapeutic drug for the treatment of dementia, especially Alzheimer's disease.
Project description:Emerging evidence suggests that an increased arginase activity is involved in vascular dysfunction in experimental animals. Zingiber officinale Roscoe, commonly known as ginger, has been widely used in the traditional medicine for treatment of diabetes.This study aimed at investigating the effects of the hydroalcoholic extract of Z. officinale on arginase I activity and expression in the retina of streptozotocin (STZ)-induced diabetic rats.In this experimental study, 16 male Wistar rats weighing 200 - 250 g were assessed. Diabetes was induced via a single intraperitoneal injection of STZ (60 mg/kg body weight). The rats were randomly allocated into four experimental groups. Untreated healthy and diabetic controls received 1.5 mL/kg distilled water. Treated diabetic rats received 200, and 400 mg/kg of the Z. officinale extract dissolved in distilled water (1.5 mL/kg). Body weight, blood glucose and insulin concentration were measured by standard methods. The arginase I activity and expression were determined by spectrophotometric and western blot analysis, respectively.Our results showed that blood glucose concentration was significantly decreased in diabetic rats treated with the extract compared to untreated diabetic controls (P < 0.01). Treatment with 400 mg/kg of the extract reduced arginase I activity and expression (P < 0.05). A significant elevation in body weight was observed in diabetic rats treated with the extract. Serum insulin was significantly increased in diabetic rats treated with 400 mg/kg of the extract compared to diabetic controls (P < 0.05).Our results suggest that the Z. officinale hydroalcoholic extract may potentially be a promising therapeutic option for treating diabetes-induced vascular disorders, possibly through reducing arginase I activity and expression in the retina.
Project description:The objective of the current project was to explore the pharmacotherapeutic role of Lavandula stoechas (L) for the management of dementia. Dementia is considered a global challenge of current century seeking special attention of pharmacologists to explore its best remedies. Methanolic extract of aerial parts of L. stoechas was tested for phytochemical analysis along with free radical scavenging activity. Behavioral studies were performed on scopolamine induced amnesic mice by using elevated plus maze (EPM), light and dark test and hole board paradigms. Biochemical investigations were made after decapitating the mice. Their brains were isolated for biochemical estimation of acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Phytochemical study ensured the presence of total phenolic contents (285.91 ± 0.75 mg of GAE/g of extract), total flavonoids (134.06 ± 0.63 mg of RE/g of extract), total tannins (149.60 ± 0.93 mg of TAE/g of extract) and free radical scavenging activity (IC50 value = 76.73 μg/ml found by DPPH method). Behavioral studies indicated that animals of GVII showed higher inflexion ratio (0.40 ± 0.03) for EPM, spent most of time (227.17 ± 2.13 s) in dark area of light dark test and had many hole pockings (39.83 ± 1.88) for hole board paradigm. Moreover, biochemical studies revealed that methanolic extract of L. stoechas (800 mg/kg/p.o.) significantly (P < 0.001) reduced brain AChE and MDA levels while improved SOD, CAT, and GSH levels. Thus the findings suggest that L. stoechas stabilizes memory by enhancing cholinergic neurotransmission and by providing defense against oxidative stress in mice brain.
Project description:Mangosteen extracts (ME) contain high levels of polyphenolic compounds and antioxidant activity. Protective effects of ME against ?-amyloid peptide (A?), 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 ?g/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.
Project description:We evaluated the neuropharmacological effects of 30% ethanolic pine needle extract (PNE) on memory impairment caused by scopolamine injection in mice hippocampus. Mice were orally pretreated with PNE (25, 50, and 100?mg/kg) or tacrine (10?mg/kg) for 7 days, and scopolamine (2?mg/kg) was injected intraperitoneally, 30 min before the Morris water maze task on first day. To evaluate memory function, the Morris water maze task was performed for 5 days consecutively. Scopolamine increased the escape latency and cumulative path-length but decreases the time spent in target quadrant, which were ameliorated by pretreatment with PNE. Oxidant-antioxidant balance, acetylcholinesterase activity, neurogenesis and their connecting pathway were abnormally altered by scopolamine in hippocampus and/or sera, while those alterations were recovered by pretreatment with PNE. As lipid peroxidation, 4HNE-positive stained cells were ameliorated in hippocampus pretreated with PNE. Pretreatment with PNE increased the proliferating cells and immature neurons against hippocampal neurogenesis suppressed by scopolamine, which was confirmed by ki67- and DCX-positive stained cells. The expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) in both protein and gene were facilitated by PNE pretreatment. These findings suggest that PNE could be a potent neuropharmacological drug against amnesia, and its possible mechanism might be modulating cholinergic activity via CREB-BDNF pathway.