Gwi Gun Park

Rubus coreanus Miquel Inhibits Acetylcholinesterase Activity and Prevents Cognitive Impairment in a Mouse Model of Dementia

To find acetylcholinesterase (AChE) inhibitors for the prevention of neurological disorders, such as Alzheimers disease, ethanol extracts of promising traditional edible Korean plants were tested. Among them, Rubus coreanus Miquel extract exhibited the most significant AChE inhibitory activity. The effect of R. coreanus extract on trimethyltin-induced memory impairment in mice was investigated using Y-maze and passive avoidance tests. Our results showed that administration of R. coreanus extract significantly improved alternation behavior and step-through latency. In addition, R. coreanus extract was sequentially fractionated, and the purified constituent was determined to be 3,4,5-trihydroxybenzoic acid.

Antioxidant and cognitive-enhancing activities of Arctium lappa L. roots in Aβ1-42-induced mouse model

Many studies have shown that oxidative stress induced by hydrogen peroxide can lead to neuronal cell death. In this study, protective effects of the ethanol extract of A. lappa L. roots against oxidative stress in PC12 cells were measured by 2′, 7′-dichlorofluorescein diacetate and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Oxidative stress contributes to the memory deficits induced by Beta-amyloid1-42 in mice. Treatment with the ethanol extract of A. lappa L. roots improved working and reference memory in mice in the Y-maze and passive avoidance tests. To detect the lipid peroxidation levels, malondialdehyde was measured. To purify the bioactive compound, active fractions and components of A. lappa L. roots were isolated by partitioning, open column chromatography, TLC, high-performance liquid chromatography, electron ionization mass spectrometry, and 1H/13C-nuclear magnetic resonance. We identified the bioactive compound as quinic acid, which is a powerful antioxidant agent. Ultimately, the roots of A. lappa L. may become available as an antioxidant food for Alzheimer’s disease patients and those with other oxidative stress-induced disorders.

Characterization of Nutritional Composition, Antioxidative Capacity, and Sensory Attributes of Seomae Mugwort, a Native Korean Variety of Artemisia argyi H. Lév. & Vaniot.

Few studies have investigated Seomae mugwort (a Korean native mugwort variety of Artemisia argyi H. Lév. & Vaniot), exclusively cultivated in the southern Korean peninsula, and the possibility of its use as a food resource. In the present study, we compared the nutritional and chemical properties as well as sensory attributes of Seomae mugwort and the commonly consumed species Artemisia princeps Pamp. In comparison with A. princeps, Seomae mugwort had higher contents of polyunsaturated fatty acids, total phenolic compounds, vitamin C, and essential amino acids. In addition, Seomae mugwort had better radical scavenging activity and more diverse volatile compounds than A. princeps as well as favorable sensory attributes when consumed as tea. Given that scant information is available regarding the Seomae mugwort and its biological, chemical, and sensory characteristics, the results herein may provide important characterization data for further industrial and research applications of this mugwort variety.

Composition of Fatty Acids in Commercially Available Tree Nuts and Their Relationship with Protective Effects against Oxidative Stress-induced Neurotoxicity

Fatty acid profiles of commercially available tree nuts were analyzed and association between fatty acid composition and protective effects against oxidative stress was investigated. Among commercially available tree nuts, walnuts showed the most potent protective effects for both cell viability and 2′,7′-dichlorofluorescein (DCF) formation. Neuronal cell viability and inhibition of intracellular oxidative stress were inversely related to saturated fatty acid contents in tree nuts. Eigen analysis revealed that principal component (PC) 1 was mainly contributed by 2′,7′-dichlorofluorescin diacetate (DCF-DA), DPPH, and C18:2 and C18:3. PC2 was contributed by MTT assay, and saturated fatty acids. Walnuts exhibited the highest potency against oxidative stress closely related with C18:3, based on principal component analysis (PCA) and Pearson’s correlation analyses. A combination of fatty acid profiling using chromatographic analysis and PCA is a promising method to evaluate oxidative stress.

Perilla frutescens Extract Ameliorates Acetylcholinesterase and Trimethyltin Chloride-Induced Neurotoxicity

One of the critical features of Alzheimers disease is cognitive dysfunction, which is, in part, due to decreases in acetylcholine (ACh). The ethanol extract of Perilla frutescens was selected for isolating the acetylcholinesterase (AChE) inhibitor based on preliminary screening. In vivo behavioral tests were performed to examine the effects of the P. frutescens extract on trimethyltin chloride-induced impairment of learning and memory in mice. A diet containing P. frutescens extract effectively reversed learning and memory impairment on the Y-maze and passive avoidance tests. To isolate the active compound from the P. frutescens extract, solvent partitioning, silica gel open column chromatography, thin-layer chromatography, and high-performance liquid chromatography were used. The AChE inhibitor was identified as rosmarinic acid.

Cinnamomum loureirii Extract Inhibits Acetylcholinesterase Activity and Ameliorates Trimethyltin-Induced Cognitive Dysfunction in Mice.

The pathogenesis of Alzheimers disease (AD) has been linked to the deficiency of neurotransmitter acetylcholine (ACh) in the brain, and the main treatment strategy for improving AD symptoms is the inhibition of acetylcholinesterase (AChE) activity. In the present study, we aimed to identify potent AChE inhibitors from Cinnamomum loureirii extract via bioassay-guided fractionation. We demonstrated that the most potent AChE inhibitor present in the C. loureirii extract was 2,4-bis(1,1-dimethylethyl)phenol. To confirm the antiamnesic effects of the ethanol extract of C. loureirii, mice were intraperitoneally injected with the neurotoxin trimethyltin (2.5 mg/kg) to induce cognitive dysfunction, and performance in the Y-maze and passive avoidance tests was assessed. Treatment with C. loureirii extract significantly improved performance in both behavioral tests, suggesting that this extract may be neuroprotective and therefore beneficial in preventing or ameliorating the degenerative processes of AD, potentially by restoring cholinergic function.

Detection of choline and phosphatidic acid (PA) catalyzed by phospholipase D (PLD) using MALDI-QIT-TOF/MS with 9-aminoacridine matrix.

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine (PC), the most abundant phospholipids of plasma membrane, resulting in the production of choline and phosphatidic acid (PA). Choline is a precursor of the neurotransmitter acetylcholine, whereas PA functions as an intracellular lipid mediator of diverse biological functions. For assessing PLD activity in vitro, PLD-derived choline has been often analyzed with radioactive or non-radioactive methods. In this study, we have developed a new method for detecting choline and PA with MALDI-QIT-TOF/MS by using 9-aminoacridine as a matrix. The standard calibration curves showed that choline and PA could be detected with linearity over the range from 0.05 and 1 pmol, respectively. Importantly, this method enables the concomitant detection of choline and PA as a reaction product of PC hydrolysis by PLD2 proteins. Thus, our simple and direct method would be useful to characterize the enzymatic properties of PLD, thereby providing insight into mechanisms of PLD activation. Graphical Abstract 9-aminoacridine is a matrix with low background and high sensitivity to analyze PA and choline by MALDI-QIT-TOF/MS.

2,4-Bis(1,1-dimethylethyl)phenol from Cinnamomum loureirii Improves Cognitive Deficit, Cholinergic Dysfunction, and Oxidative Damage in TMT-Treated Mice

We previously reported that the extract of Cinnamomum loureirii (C. loureirii) significantly inhibited acetylcholinesterase (AChE), and identified 2,4-bis(1,1-dimethylethyl)phenol (BP) from C. loureirii as a potential AChE inhibitor. The present study, therefore was undertaken to demonstrate the effects of BP from C. loureirii on learning and memory impairment in trimethyltin (TMT)-treated ICR mice. Y-maze and passive avoidance tests were used to test cognitive ability. Further, changes in biochemical parameters in the brain tissue were also assessed in response to TMT injection and BP intervention. BP pre-administration (20, 40 mg/kg/d) in mice significantly protected cognitive dysfunction induced by TMT (p<0.05). Moreover, BP reduced AChE activity and lipid peroxidation but increased acetylcholine levels in the brain. In conclusion, we suggested that BP protected against TMT-induced cognitive dysfunction, and might be a potential agent for alleviating symptoms of neurodegenerative disorders, such as Alzheimers disease, via modulating cholinergic functions.

Effect of Chaenomeles sinensis Extract on Choline Acetyltransferase Activity and Trimethyltin-Induced Learning and Memory Impairment in Mice.

The aim of this study was to search for a novel choline acetyltransferase (ChAT) activator from plants traditionally grown in Korea. An ethanol extract from Chaenomeles sinensis Koehne showed the highest ChAT-activating effect in vitro in an assay that used human neuroblastoma cells and [(14)C]acetyl-CoA. The active compound was speculated to be stearic acid methyl ester (SAME). In an in vivo experiment, C. sinensis extract and SAME improved trimethyltin (TMT)-induced deficits in learning and memory in mice as assessed by a Y-maze behavioral test and a passive avoidance test. The C. sinensis extract might attenuate the TMT-induced brain disorder. This study suggests that SAME from C. sinensis might be useful in the treatment of Alzheimers disease.

Application of response surface methodology to optimize the extraction of acetylcholinesterase inhibitors from Rhodiola sachalinensis

Response surface methodology (RSM) was utilized to optimize extraction conditions for the acetylcholinesterase inhibitor from Rhodiola sachalinensis. Optimized values for AChE inhibition and extraction yield were 19.41 and 13.35%, respectively, and these were in good agreement with the experimental values from validation, suggesting that RSM is a useful tool.