• Korean Journal of Food Science and Technology
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• v.51 no.2
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• pp.160-168
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• 2019

This study aimed to determine whether double-processed ginseng berry extract (PGBC) could improve learning and memory in an $A\hat{a}42$-induced Alzheimer's mouse model. Passive avoidance test (PAT) and Morris water-maze test (MWMT) were performed after mice were treated with PGBC, followed by acetylcholine (ACh) measurement and glial fibrillary acidic protein (GFAP) detection for brain damage. Furthermore, acetylcholinesterase (AChE) activity and choline acetyltransferase (ChAT) expression were analyzed using Ellman's and qPCR assays, respectively. Results demonstrated that PGBC contained a high amount of ginsenosides (Re, Rd, and Rg3), which are responsible for the clearance of $A{\hat{a}} 42$. They also helped to significantly improve PAT and MWMT performance in the $A{\hat{a}} 42-induced$ Alzheimer's mouse model when compared to the normal group. Interestingly, ACh and ChAT were remarkably upregulated and AChE activities were significantly inhibited, suggesting PGBC to be a palliative adjuvant for treating Alzheimer's disease. Altogether, PGBC was found to play a positive role in improving cognitive abilities. Thus, it could be a new alternative solution for alleviating Alzheimer's disease symptoms.

• Korean Journal of Pharmacognosy
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• v.50 no.4
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• pp.253-259
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• 2019

Chaenomeles speciose Nakai (CSP) or Chaenomeles sinensis Koehne (CSS) (Rosaceae) has been used, traditionally, to treat muscle problems and gastric dampness in eastern Asia countries. Therefore, many studies have focused on investigating its active compounds and effects on muscle pain, arthritis and gastro-intestinal diseases. Recently, several studies reported that CSS extract degrade amyloid plaques and enhance synaptic acetylcholine level in vivo and in vitro. Although these two Chaenomeles species are used without differences, CSP is reported to contains more phenolic compounds which are known to enhance memory. Therefore, in this study, we investigated the memory ameliorating effects of CSP by employing the passive avoidance test, Y-maze task and novel object recognition test. CSP (30 or 100 mg/kg) ameliorated the declined memory induced by scopolamine injection and enhanced the brain-derived neurotrophic factor (BDNF) levels along with post synaptic density protein 95 (PSD 95) levels at the hippocampus of the scopolamine-injected mouse brain. These results suggested that CSP alleviates the cognition declines caused by cholinergic blockade via enhancing BDNF levels and PSD 95, and that it would enhance memory formation and be useful for treating memory declines.

• Biomolecules & Therapeutics
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• v.21 no.5
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• pp.381-390
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• 2013

The purpose of this study was to examine whether ginsenoside Rg3 (GRg3) could improve learning and memory impairments and inflammatory reactions induced by injecting lipopolysaccharide (LPS) into the brains of rats. The effects of GRg3 on proinflammatory mediators in the hippocampus and the underlying mechanisms of these effects were also investigated. Injection of LPS into the lateral ventricle caused chronic inflammation and produced deficits in learning in a memory-impairment animal model. Daily administration of GRg3 (10, 20, and 50 mg/kg, i.p.) for 21 consecutive days markedly improved the LPS-induced learning and memory disabilities demonstrated on the step-through passive avoidance test and Morris water maze test. GRg3 administration significantly decreased expression of pro-inflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-1${\beta}$, and cyclooxygenase-2 in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. Together, these findings suggest that GRg3 significantly attenuated LPS-induced cognitive impairment by inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggest that GRg3 may be effective for preventing or slowing the development of neurological disorders, including Alzheimer's disease, by improving cognitive and memory functions due to its anti-inflammatory activity in the brain.

• Journal of Microbiology and Biotechnology
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• v.21 no.8
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• pp.874-883
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• 2011

Many studies have shown that the steamed root of Rehmannia glutinosa (SRG), which is widely used in the treatment of various neurodegenerative diseases in the context of Korean traditional medicine, is effective for improving cognitive and memory impairments. The purpose of this study was to examine whether SRG extracts improved memory defects caused by administering scopolamine (SCO) into the brains of rats. The effects of SRG on the acetylcholinergic system and proinflammatory cytokines in the hippocampus were also investigated. Male rats were administered daily doses of SRG (50, 100, and 200 mg/kg, i.p.) for 14 days, 1 h before scopolamine injection (2 mg/kg, i.p.). After inducing cognitive impairment via scopolamine administration, we conducted a passive avoidance test (PAT) and the Morris water maze (MWM) test as behavioral assessments. Changes in cholinergic system reactivity were also examined by measuring the immunoreactive neurons of choline acetyltransferase (ChAT) and the reactivity of acetylcholinesterase (AchE) in the hippocampus. Daily administration of SRG improved memory impairment according to the PAT, and reduced the escape latency for finding the platform in the MWM. The administration of SRG consistently significantly alleviated memory-associated decreases in cholinergic immunoreactivity and decreased interleukin-$1{\beta}$ (IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) mRNA expression in the hippocampus. The results demonstrated that SRG had a significant neuroprotective effect against the neuronal impairment and memory dysfunction caused by scopolamine in rats. These results suggest that SRG may be useful for improving cognitive functioning by stimulating cholinergic enzyme activities and alleviating inflammatory responses.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.2
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• pp.79-89
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• 2012

We examine whether Phellodendron amurense (PA) and its major alkaloid compound, berberine (BER), improved memory defects caused by administering scopolamine in rats. Effects of PA and BER on the acetylcholinergic system and pro-inflammatory cytokines in the hippocampus were also investigated. Male rats were administered daily doses for 14 days of PA (100 and 200 mg/kg, i.p.) and BER (20 mg/kg, i.p.) 30 min before scopolamine injection (2 mg/kg, i.p.). Daily administration of PA and BER improved memory impairment as measured by the passive avoidance test and reduced the escape latency for finding the platform in the Morris water maze test. Administration of PA and BER significantly alleviated memory-associated decreases in cholinergic immunoreactivity and restored brain-derived neurotrophic factor and cAMP-response element-binding protein mRNA expression in the hippocampus. PA and BER also decreased significantly the expression of proinflammatory cytokines such as interleukin-$1{\beta}$, tumor necrosis factor-${\alpha}$ and cyclooxygenase-2 mRNA in the hippocampus. These results demonstrated that PA and BER had significant neuroprotective effects against neuronal impairment and memory dysfunction caused by scopolamine in rats. These results suggest that PA and BER may be useful as therapeutic agents for improving cognitive functioning by stimulating cholinergic enzyme activity and alleviating inflammatory responses.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.55-64
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• 2017

Progressive memory impairment such as that associated with depression, stroke, and Alzheimer's disease (AD) can interfere with daily life. In particular, AD, which is a progressive neurodegenerative disorder, prominently features a memory and learning impairment that is related to changes in acetylcholine and abnormal ${\beta}$-amyloid ($A{\beta}$) deposition in the brain. In the present study, we investigated the effects of dehydroevodiamine HCl (DHED) on cognitive improvement and the related mechanism in memory-impaired rat models, namely, a scopolamine-induced amnesia model and a $A{\beta}_{1-42}$-infused model. The cognitive effects of DHED were measured using a water maze test and a passive avoidance test in the memory-impaired rat models. The results demonstrate that DHED (10 mg/kg, p.o.) and Donepezil (1 mg/kg, p.o.) ameliorated the spatial memory impairment in the scopolamine-induced amnestic rats. Moreover, DHED significantly improved learning and memory in the $A{\beta}_{1-42}$-infused rat model. Furthermore, the mechanism of these behavioral effects of DHED was investigated using a cell viability assay, reactive oxygen species (ROS) measurement, and intracellular calcium measurement in primary cortical neurons. DHED reduced neurotoxicity and the production of $A{\beta}$-induced ROS in primary cortical neurons. In addition, similar to the effect of MK801, DHED decreased intracellular calcium levels in primary cortical neurons. Our results suggest that DHED has strong protective effects against cognitive impairments through its antioxidant activity and inhibition of neurotoxicity and intracellular calcium. Thus, DHED may be an important therapeutic agent for memory-impaired symptoms.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.47 no.3
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• pp.195-203
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• 2014

We investigated the effect low salt (2 or 4% salt) concentrations jeotgal made from Todarodes pacificus on the learning and memory impairments in scopolamine-induced (2 mg/kg, i.p.) dementia rats. Rats treated with oral BF-7 (200 mg/kg, p.o.) as a positive control and Todarodes pacificus jeotgal had significantly reduced scopolamine-induced memory deficits in the passive avoidance test. The Morris water maze test or treatment with 2% salt jeotgal made from Todarodes pacificus significantly ameliorated the scopolamine-induced memory deficits in the formation of long- and short-term memory. The acetylcholine content and acetylcholinesterase acitivity paralleled the results of the behavior experiment. There were no significant differences in the brain acetylcholine contents of the experimental groups, while the brain acetylcholine content of the group treated with 2% salt Todarodes pacificus jeotgal was higher than that of the control group. The inhibitory effect of 2% salt jeotgal made from Todarodes pacificus on the acetylcholinesterase activity in the brain was lower than that of the control group. These trends were similar to those of the gamma-aminobutyric acid content. We suggest that Todarodes pacificus jeotgal enhances learning memory and cognitive function by regulating cholinergic enzymes.

• Food Science of Animal Resources
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• v.40 no.2
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• pp.183-196
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• 2020

The protective effect of pig skin gelatin water extracts (PSW) and the low molecular weight hydrolysates of PSW generated via enzymatic hydrolysis with Flavourzyme® 1000L (LPSW) against scopolamine-induced impairment of cognitive function in mice was determined. Seventy male ICR mice weighing 20-25 g were randomly assigned to seven groups: Control (CON); scopolamine (SCO, 1 mg/kg B.W., intraperitoneally (i.p.); tetrahydroaminoacridine 10 [THA 10, tacrine; 10 mg/kg B.W. per oral (p.o.) with SCO (i.p.)]; PSW 10 (10 mg/kg B.W. (p.o.) with SCO (i.p.); PSW 40 (40 mg/kg B.W. (p.o.) with SCO (i.p.); LPSW 100 (100 mg/kg B.W. (p.o.) with SCO (i.p.); LPSW 400 (400 mg/kg B.W. (p.o.) with SCO (i.p.). All treatment groups, except CON, received scopolamine on the day of the experiment. The oxygen radical absorbance capacity of LPSW 400 at 1 mg/mL was 154.14 μM Trolox equivalent. Administration of PSW and LPSW for 15 weeks did not significantly affect on physical performance of mice. LPSW 400 significantly increased spontaneous alternation, reaching the level observed for THA and CON. The latency time of animals receiving LPSW 400 was higher than that of mice treated with SCO alone in the passive avoidance test, whereas it was shorter in the water maze test. LPSW 400 increased acetylcholine (ACh) content and decreased ACh esterase activity (p<0.05). LPSW 100 and LPSW 400 reduced monoamine oxidase-B activity. These results indicated that LPSW at 400 mg/kg B.W. is a potentially strong antioxidant and contains novel components for the functional food industry.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.1
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• pp.47-57
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• 2022

Stiripentol is an anti-epileptic drug for the treating of refractory status epilepticus. It has been reported that stiripentol can attenuate seizure severity and reduce seizure-induced neuronal damage in animal models of epilepsy. The objective of the present study was to investigate effects of post-treatment with stiripentol on cognitive deficit and neuronal damage in the cornu ammonis 1 (CA1) region of the hippocampus proper following transient ischemia in the forebrain of gerbils. To evaluate ischemia-induced cognitive impairments, passive avoidance test and 8-arm radial maze test were performed. It was found that post-treatment with stiripentol at 20 mg/kg, but not 10 or 15 mg/kg, reduced ischemia-induced memory impairment. Transient ischemia-induced neuronal death in the CA1 region was also significantly attenuated only by 20 mg/kg stiripentol treatment after transient ischemia. In addition, 20 mg/kg stiripentol treatment significantly decreased ischemia-induced astrocyte damage and immunoglobulin G leakage. In brief, stiripentol treatment after transient ischemia ameliorated transient ischemia-induced cognitive impairment in gerbils, showing that pyramidal neurons were protected and astrocyte damage and blood brain barrier leakage were significantly attenuated in the hippocampus. Results of this study suggest stiripentol can be developed as a candidate of therapeutic drug for ischemic stroke.

• Nutrition Research and Practice
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• v.17 no.2
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• pp.192-205
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• 2023

BACKGROUND/OBJECTIVES: It is known that the renin-angiotensin system (RAS) in the brain could regulate cognitive functions as well as blood pressure. Inhibition of RAS for the improvement of cognitive function may be a new strategy, but studies so far have mostly reported on the effects of RAS inhibition by drugs, and there is no research on cognitive improvement through RAS inhibition of food ingredients. Therefore, this study investigated the effect of curcumin on blood pressure and cognitive function and its related mechanism in spontaneously hypertensive rat/Izm (SHR/Izm). MATERIALS/METHODS: Six-week-old SHR/Izm rats were divided into 5 groups: control group (CON), scopolamine group (SCO, drug for inducing cognitive deficits), positive control (SCO and tacrine [TAC]), curcumin 100 group (CUR100, SCO + Cur 100 mg/kg), and curcumin 200 group (CUR200, SCO + Cur 200 mg/kg). Changes in blood pressure, RAS, cholinergic system, and cognitive function were compared before and after cognitive impairment. RESULTS: The SCO group showed increased blood pressure and significantly reduced cognitive function based on the y-maze and passive avoidance test. Curcumin treatments significantly improved blood pressure and cognitive function compared with the SCO group. In both the CUR100 and CUR200 groups, the mRNA expressions of angiotensin-converting enzyme (ACE) and angiotensin II receptor type1 (AT1), as well as the concentrations of angiotensin II (Ang II) in brain tissue were significantly decreased. The mRNA expression of the muscarinic acetylcholine receptors (mAChRs) and acetylcholine (ACh) content was significantly increased, compared with the SCO group. CONCLUSIONS: The administration of curcumin improved blood pressure and cognitive function in SCO-induced hypertensive mice, indicating that the cholinergic system was improved by suppressing RAS and AT1 receptor expression and increasing the mAChR expression.