• Biomolecules & Therapeutics
• /
• v.12 no.2
• /
• pp.101-107
• /
• 2004

Repeated administration of psychostimulants such as amphetamines increases locomotor activity in rodents. These drugs, including methamphetamine, enhance dopaminergic neurotransmission and result in hyper-locomotion and behavioral sensitization. It is well known that the existence of a complex balance between the cholinergic and dopaminergic systems in the central nervous system. Thus, behavioral sensitization by methamphetamine may be related to the expression of the M1 muscarinic acetylcholine receptors gene. The present study investigated the changes of M1R mRNA in hyperlocomotor activity and behavioral sensitization by methamphetamine (2 mg/kg) in mice. Our results showed that M1R mRNA expression was increased in the frontal cortex and the hippocampus region (the CA2 region) in the acute methamphetamine administered group compared to the saline administered group. In the chronic group, M1R mRNA expression was increased in the frontal cortex ill1d the hippocampus regions (CA2 and DG regions) in melt1amphetamine administered group compared to saline control group. These results indicate that acute or chronic treatment of mathamphetamine leads to the region-specific changes in mRNA expression levels of M1R. Therefore, Therefore, the present result suggests that M1R may play a role in modulating of methamphetamine-induced behavioral sensitization in mice.

• Advances in Traditional Medicine
• /
• v.7 no.2
• /
• pp.182-190
• /
• 2007

Alzheimer's disease is a neurodegenerative disorder associated with a decline in cognitive abilities. Dementia is one of the aged related mental problems and a characteristic symptom of Alzheimer's disease. Nootropic agents like piracetam and cholinesterase inhibitors like $Donepezil^{\circledR}$ are used in situations where there is organic disorder in learning abilities, but the resulting side-effects associated with these agents have limited their utility. Foeniculum (F.) vulgare Linn. is widely used in Indian traditional systems of medicines and also as a house remedy for nervous debility. The present work was undertaken to assess the potential of F. vulgare as a nootropic and anti-cholinesterase agent in mice. Exteroceptive behavioral models such as Elevated plus maze and Passive avoidance paradigm were employed to assess short term and long term memory in mice. To delineate the possible mechanism through which F. vulgare elicits the anti-amnesic effects, its influence on central cholinergic activity was studied by estimating the whole brain acetylcholinesterase activity. Pretreatment of methanolic extract of fruits of F. vulgare Linn. for 8 successive days, ameliorated the amnesic effect of scopolamine (0.4 mg/kg) and aging induced memory deficits in mice. F. vulgare extract significantly decreased transfer latencies of young mice and aged mice, increased step down latency and exhibited significant anti-acetyl cholinesterase effects, when compared to piracetam, scopolamine and control groups of mice. F. vulgare might prove to be a useful memory restorative agent in the treatment of dementia seen in the elderly.

• Journal of Marine Life Science
• /
• v.8 no.1
• /
• pp.78-86
• /
• 2023

Here, upon acute (96 h) and chronic (14 days) exposure, ingestion of polystyrene NPs (100 nm) and physiological, biochemical, and cholinergic modulations were analyzed in the water flea Moina macrocopa exposed to different concentrations (0.001, 0.01, 0.1, 1, 5, 10, 50, 100, and 500 ㎍ l^-1). Exposed NPs were observed in the internal organs (e.g., digestive tract and foregut) of the water flea. Chronic exposure to the relatively high concentrations resulted in significant decreases in survival, body length, and the total number of molts, whereas reproduction parameter was not affected. Significant increase in oxidative stress biomarker (malondialdehyde) and decrease in the intracellular content of endogenous antioxidant (glutathione) and enzymatic activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase, and glutathione S-transferase) were detected in response to relatively high concentrations of NPs. Transcriptional expression of the hsp70 gene was increased in response to relatively high concentrations of NPs, whereas acetylcholinesterase activity was lowered by the same concentrations of NPs. Taken together, NPs exposure would be a significant modulator on physiological and biochemical metabolism of water flea.

• Journal of Ginseng Research
• /
• v.34 no.1
• /
• pp.51-58
• /
• 2010

This study compared the effects of black, white, and red ginseng extracts (WGE, RGE, BGE, 200 mg/kg, p.o.) on learning and memory deficits associated with scopolamine treatment (SCOP, 2 mg/kg, i.p.). Tacrine (THA, 10 mg/kg, p.o.) was used as a positive control. Ginseng significantly reversed SCOP-induced memory impairment in the passiveavoidance test and also reduced escape latency in training trials of the Morris water maze test. The increased acetylcholinesterase (AChE) activity produced by SCOP was significantly inhibited by WGE and RGE (p<0.001). SCOP administration had no effect on choline acetyltransferase (ChAT) activity, but RGE and BGE significantly increased ChAT activity (p<0.05). SCOP administration increased oxidative damage in the brain. Treatment of amnesic mice with ginseng extracts decreased malondialdehyde (MDA) levels and restored superoxide dismutase (SOD) and catalase (CAT) activity to control levels. These results suggest that black ginseng enhances cognitive activity by regulation of cholinergic enzymes and antioxidant systems.

• Korean Journal of Food Science and Technology
• /
• v.51 no.4
• /
• pp.379-392
• /
• 2019

The current study investigated the effect of Gabjubaekmok (Diospyros kaki) ethanolic extract (GEE) on $H_2O_2$-induced human neuroblastoma MC-IXC cells and amyloid beta $(A{\beta})_{1-42}$-induced ICR (Institute of Cancer Research) mice. GEE showed significant antioxidant activity that was evaluated based on ABTS, DPPH scavenging activity, and inhibition of malondialdehyde (MDA) and acetylcholinesterase activity. Further, GEE inhibited ROS production and increased cell viability in $H_2O_2$-induced MC-IXC cells. Administration of GEE ameliorated the cognitive dysfunction on $A{\beta}$-induced ICR mice as evaluated using Y-maze, passive avoidance, and Morris water maze tests. Results of ex vivo test using brain tissues showed that, GEE protected the cholinergic system and mitochondrial functions by increasing the levels of antioxidants such as ROS, mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP) against $A{\beta}$-induced cognitive dysfunction. Moreover, GEE decreasd the expression levels of apoptosis-related proteins such as $TNF-{\alpha}$, p-JNK, p-tau, BAX and caspase 3. While, expression levels of p-Akt and $p-GSK3{\beta}$ increased than $A{\beta}$ group. Finally, gallic acid was identified as the main compound of GEE using high performance liquid chromatography.

• Journal of Ginseng Research
• /
• v.42 no.4
• /
• pp.401-411
• /
• 2018

Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid ${\beta}$-protein ($A{\beta}$) formation by inhibiting ${\beta}$- and ${\gamma}$-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and $A{\beta}$-induced neurotoxicity, and decrease $A{\beta}$-induced production of reactive oxygen species and neuro-inflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates $A{\beta}$-induced cholinergic deficits in AD models. Similarly, gintonin inhibits $A{\beta}$-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce $A{\beta}$ formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.

• Journal of Pharmacopuncture
• /
• v.22 no.4
• /
• pp.231-238
• /
• 2019

Objectives: Alzheimer's disease (AD), an overwhelming neurodegenerative disease, has deleterious effects on the brain that consequently causes memory loss and language impairment. This study was intended to investigate the neuroprotective activity of the two essential oils (EOs) from Iranian Pistacia khinjuk (PK) leaves and Allium sativum (AS) cloves against β-Amyloid 25-35 (Aβ25-35) induced elevation of cholinesterase enzymes in AD. Methods: The EOs of PK (PKEO) and AS (ASEO) were prepared and analyzed in terms of extraction yield, phenolic content, and cholinergic markers in vitro. Moreover, both were administered orally to adult male Wistar rats at concentrations of 1, 2, and 3%. The inhibitory potential of PKEO and ASEO was compared with Donepezil (0.75 mg/kg) against the high activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Results: PKEO reached an inhibition rate of 83.6% and 81.4% against AChE and BChE, respectively. ASEO had lower anti-cholinesterase activity (65.4% and 31.5% for the inhibition AChE and BChE). PKEO was found to have more phenolic content than ASEO. A significantly positive correlation was observed between the total phenolics and anti-cholinesterase potential. In rats, both EOs decreased the enzyme activity in a concentration-dependent manner. As compared with Donepezil, the significant difference in the AChE and BChE inhibition occurred as rats were treated with PKEO 3% (p < 0.05). Conclusion: It could be concluded that PKEO and ASEO are potent inhibitors of AChE and BChE in rats that hold promise to be used for the treatment of AD.

• Journal of Microbiology and Biotechnology
• /
• v.28 no.1
• /
• pp.40-49
• /
• 2018

We evaluated the antioxidant activity and neuronal cell-protective effect of fucoidan extract from Ecklonia cava (FEC) on hydrogen peroxide ($H_2O_2$)-induced cytotoxicity in PC-12 and MC-IXC cells to assess its protective effect against oxidative stress. Antioxidant activities were examined using the ABTS radical scavenging activity and malondialdehyde-inhibitory effect, and the results showed that FEC had significant antioxidant activity. Intracellular ROS contents and neuronal cell viability were investigated using the DCF-DA assay and MTT reduction assay. FEC also showed remarkable neuronal cell-protective effect compared with vitamin C as a positive control for both $H_2O_2$-treated PC-12 and MC-IXC cells. Based on the neuronal cell-protective effects, mitochondrial function was analyzed in PC-12 cells, and FEC significantly restored mitochondrial damage by increasing the mitochondrial membrane potential (${\Delta}{\Psi}m$) and ATP levels and regulating mitochondrial-mediated proteins (p-AMPK and BAX). Finally, the inhibitory effects against acetylcholinesterase (AChE), which is a critical hydrolyzing enzyme of the neurotransmitter acetylcholine in the cholinergic system, were investigated ($IC_{50}$ value = 1.3 mg/ml) and showed a mixed (competitive and noncompetitive) pattern of inhibition. Our findings suggest that FEC may be used as a potential material for alleviating oxidative stress-induced neuronal damage by regulating mitochondrial function and AChE inhibition.

• Biomolecules & Therapeutics
• /
• v.20 no.2
• /
• pp.207-213
• /
• 2012

The present study examined the effects of krill-derived phosphatidylserine (Krill-PS) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The rats were administered vehicle (medium-chain triglyceride: MCT) or Krill-PS (50, 100 mg/kg, p.o.) daily for 21 days. The cognitive improving efficacy of Krill-PS in TMT-induced amnesic rats was investigated by assessing the Morris water maze test and by performing choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and cAMP responsive element binding protein (CREB) immunohistochemistry. The rats with TMT injection showed impaired learning and memory of the tasks and treatment with Krill-PS produced a significant improvement of the escape latency to find the platform in the Morris water maze at the $2^{nd}$ and $4^{th}$ day compared to that of the MCT group (p<0.05). In the retention test, the Krill-PS+MCT groups showed increased time spent around the platform compared to that of the MCT group. Consistent with the behavioral data, Krill-PS 50+MCT group significantly alleviated the loss of acetylcholinergic neurons in the hippocampus and medial septum compared to that of the MCT group. Treatment with Krill-PS significantly increased the CREB positive neurons in the hippocampal CA1 area as compared to that of the MCT group. These results suggest that Krill-PS may be useful for improving the cognitive function via regulation of cholinergic marker enzyme activity and neural activity.

• The Korean Journal of Physiology
• /
• v.14 no.2
• /
• pp.21-28
• /
• 1980

In order to investigate the effect of cholinergic substance on the electrical and the mechanical activities of the stomach muscle, 10 isolated cat stomachs were studied. At various sites of a stomach muscle preparation, the electrical activity was monopolarly recorded by using capillary electrodes containing chlorided silver wires, and the isometric contractile activity was recorded simultaneously at the terminal portion of the antrum in Krebs solution$(36^{\circ}C)$ which was aerated with a gas mixture consisting of 95% $O_2$ and 5% $CO_2$. The recording of these activities were performed before (control period) and after acetylcholine$(10^{-5}M)$ and atropine $(10^{-6}M)$ administrations serially. Following results were obtained: 1) The mean frequency of the slow wave was $4.36{\pm}0.22\;cycles/min$ at all the various sites of the cat stomach. The slow wave was propagated caudad in sequence and its velosity of propagation increased as the slow wave approached the pylorus in normal Krebs solution. 2) After acetylcholine administration, the frequency of the slow wave increased transiently and the increase of slow wave frequency was followed by the isometric contraction of antral muscle in association with the second potential which succeeded the slow wave. 3) By atropine administration, the stimulatory effect of acetylcholine on the antral muscle contraction was abolished completely, and the frequency of the slow wave decreased significantly compared with that of the control period, which tendency was more prominent in the antrum. The above results suggest that the transient increase in the frequency of gastric slow wave by acetylcholine may have some influence upon the contraction mechanism of the cat antral muscle.