• The Korea Journal of Herbology
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• v.36 no.6
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• pp.1-8
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• 2021

Objectives : Atractylodis rhizoma Alba has been traditionally used as a medicinal resource that is used for enhancing Qi (氣) in traditional medicine in Korea, China, and Japan. This study investigated the protective effects of Atractylodis rhizoma Alba extract (ARE) against trimethyltin (TMT), a neurotoxin that causes selective hippocampal injury, using both in vitro and in vivo models. Methods : We investigated the effects of ARE on TMT- (5mM) induced cytotoxicity in primary cultures of mouse hippocampal cells (7 days in vitro ) and on hippocampal injury in C57BL/6 mice injected with TMT (2.6 mg/kg). Results : We observed that ARE treatment (0 - 50 ㎍/mL) significantly reduced TMT-induced cytotoxicity in cultured hippocampal neurons in a dose-dependent manner, based on results of lactate dehydrogenase and 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assays. Additionally, this study showed that orally administered ARE (5 mg/kg; between -6 and 0 days before TMT injection) significantly attenuated seizures in adult mice. Furthermore, quantitative analysis of allograft inflammatory factor-1 (Iba-1)- and glial fibrillary acidic protein (GFAP)- positive cells showed significantly reduced levels of Iba-1- and GFAP-positive cell bodies in the dentate gyrus of mice treated with ARE prior to TMT injection. These findings indicate the significant protective effects of ARE against the TMT-induced massive activation of microglia and astrocytes in the hippocampus. Conclusions : We conclude that ARE minimizes the detrimental effects of TMT-induced hippocampal neurotoxicity, both in vitro and in vivo . Our findings may serve as useful guidelines to support ARE administration as a promising pharmacotherapeutic approach to hippocampal degeneration.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.3
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• pp.337-345
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• 2014

The present study examined the effects of soybean-derived phosphatidylserine (SB-PS) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The cognitive improving efficacy of SB-PS on the amnesic rats, which was induced by TMT, was investigated by assessing the Morris water maze test and by performing cholineacetyl transferase (ChAT), acetylcholinesterase (AChE) and cAMP responsive element binding protein (CREB) immunohistochemistry. A positron emission tomography (PET) scanning the rat brain was by performed administer 18F-Fluorodeoxy-glucose (18F-FDG). The rats with TMT injection showed impaired learning and memory of the tasks and treatment with SB-PS produced a significant improvement of the escape latency to find the platform in the Morris water maze at the 2nd day compared to that of the MCT group. In the retention test, the SB-PS group showed increased time spent around the platform compared to that of the MCT group. Consistent with the behavioral data, SB-PS 50 group significantly alleviated the loss of acetyl cholinergic neurons in the hippocampus compared to that of the MCT group. Treatment with SB-PS significantly increased the CREB positive neurons in the hippocampus as compared to that of the MCT group. In addition, SB-PS groups increased the glucose uptake in the hippocampus and SB-PS 50 group increased the glucose uptake in the frontal lobe, as compared to that of the MCT group. These results suggest that SB-PS may be useful for improving the cognitive function via regulation of cholinergic marker enzyme activity and neural activity.

• Korean Journal of Medicinal Crop Science
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• v.25 no.6
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• pp.353-360
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• 2017

Background: A critical features of Alzheimer's disease (AD) is cognitive dysfunction, which partly arises from decreased in acetylcholine levels. AD afftected brains are characterized by extensive oxidative stress, which is thought to be primarily induced by the amyloid beta ($A{\beta}$) peptide. In a previous study, Cinnamomum loureiroi tincture inhibited acetylcholinesterase (AchE) activity. That study identified AChE inhibitor in the C. loureiroi extract. Furthermore, the C. loureiroi extract enhanced memory in a trimethyltin (TMT)-induced model of cognitive dysfunction, as assessed via two behavioral tests. Rosa laevigata extract protected against oxidative stress-induced cytotoxicity. Administrating R. laevigata extracts to mice significantly reversed $A{\beta}$-induced learning and memory impairment, as shown in behavioral tests. Methods and Results: We conducted behavioral to examine the synergistic effects of C. loureiroi and R. laevigata extracts in inhibiting AChE and counteracting TMT-induced learning and memory losses. We also performed biochemical assays. The biochemical results showed a relationship between increased oxidative stress and cholinergic neurons damage in TMT-treated mice. Conclusions: A diet containing C. loureiroi and R. laevigata extracts ameliorated learning and memory impairments in the Y-maze and passive avoidance tests, and exerted synergistic inhibitory effect against AChE and lipid peroxidation.

• ALGAE
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• v.31 no.1
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• pp.73-84
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• 2016

Marine organisms are frequently used to be harmful and have lower side effects than synthetic drugs. The cognitive improving efficacy of gamma aminobutyric acid-enriched fermented Saccharina japonica (FSJ) on the memory deficient rats, which were induced by trimethyltin chloride (TMT), was investigated by assessing the Morris water maze test and by performing choline acetyltransferase (ChAT), cAMP response element binding protein (CREB), and brain derived neurotrophic factor (BDNF) immunohistochemistry. The neurite outgrowth of Neuro2a cells was assessed in order to examine the underlying mechanisms of the memory enhancing effects of FSJ. Treatment with FSJ tended to shorten the latency to find the platform in the acquisition test of the Morris water maze at the second and fourth day compared to the control group. In the probe trial, the FSJ treated group increased time spent in the target quadrant, compared to that of the control group. Consistent with the behavioral data, these treatments recovered the loss of ChAT, CREB, and BDNF immunepositive neurons in the hippocampus produced by TMT. Treatment with FSJ markedly stimulated neurite outgrowth of the Neuro2a cells as compared to that of the controls. These findings demonstrate that FSJ may be useful for improving the cognitive function via regulation of neurotrophic marker enzyme activity.

• The Korean Journal of Food And Nutrition
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• v.29 no.3
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• pp.382-391
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• 2016

The purpose of this experiment was designed to investigate the effects of medicinal herbs (MH) extracts on dementia induced by trimethyltin chloride (TMT) in rats. Six-week-old male Sprague-Dawley rats were randomly divided into five groups; normal group (group 1), control group (group 2), MH extracts group (250, 500 mg/kg) (group 3, group 4) and positive control group (tacrine group, group 5). In the control group to induce dementia, a 2.5 mg/kg of TMT intraperitoneal injection was used for 14 days (1 per day) in the rats. In the MH extracts group 250 mg/kg and 500 mg/kg of MH extracts were medicated in an oral inoculation for 20 days (1 per day). After 30 minutes, a 2.5 mg/kg of TMT intraperitoneal injection, which causes dementia, was used for 14 days (1 per day). In the positive control group (Tacrine group) 10 mg/kg of Tacrine, the dementia treatment, was medicated in an oral inoculation. After 30 mintues, 1 mg/kg of TMT intraperitoneal injection, which causes dementia, was used for 14 days (1 per day). The present author observed the passive avoidance performance test, and memory ability test (Y maze test), the values of MDA, acetlycholinesterase (AchE) activity in the brain and antioxidant enzyme in serum. MH extracts significantly improved memory of AD model rats in the Y-maze test, and also significantly improved memory of AD model rats in the passive avoidance test. MH extracts significantly reduced AChE activity, and significantly increased the SOD level, but not catalase and MDA. From the results above, MH extracts is thought to be effective in the improvement of antioxidant enzymes and memory ability.

• Korean Journal of Food Science and Technology
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• v.47 no.3
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• pp.380-387
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• 2015

The anti-amnesic effect of Artemisia argyi H against trimethyltin (TMT)-induced learning and memory impairment and its neuroprotective effect against $H_2O_2$-inducedoxidative stress were investigated. Cognitive behavior was examined by Y-maze and passive avoidance test for 4 weeks, which showed improved cognitive functions in mice treated with the extract. In vitro neuroprotective effects against $H_2O_2$-induced oxidative stress were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromide and lactate dehydrogenase (LDH) assays. A. argyi H. extract showed protective effects against $H_2O_2$-induced neurotoxicity; moreover, LDH release into the medium was inhibited. Finally, high-performance liquid chromatography (HPLC) analysis showed that eupatilin and jaceosidin were the major phenolic compounds in A. argyi H. extract. These results suggest that A. argyi H. could be a good source of functional substances to prevent neurodegenerative diseases.

• Toxicological Research
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• v.11 no.2
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• pp.315-327
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• 1995

Diverse neurotoxic insults result in proliferation and hypertrophy of astrocytes, a subtype of glia in central nervous system. The hallmark of this response, often terms "reactive gliosis", is the enhanced expression of the major intermediate filament protein of castrocytes, glial fibrillary acidic protein (GFAP). These changes in the astrocytes suggest that GFAP may be a useful biochemical indicator of neurotoxicity. To investigate this possibility, we administered intra-peritoneally prototype nerotoxicants, metharnphetamine (MAP, 5 mg/kg), cocaine (30 mg/kg), N-buthyl benzenesulfonamide (NBBS, 300 mg/kg) and trimethytin (TMT, 8 mg/kg) to Wistar Rats and then assessed the effects of these agents on content of GFAP, which were determined by Sandwish ELISA and evaluated with neurotoxic symptoms, and quantitative changes of imrnunoreactivity of GFAP by light microscopic image analysis in specific regions. We found that assay of GFAP revealed time- and region-dependant patterns of neurotoxicity. The GFAP immunoreactivity of rat brain was increased in substantia nigra and hippocampus by MAP, NBBS and TMT; in roedial septal nucleus and nucleus accurnbens, it was also increased by RrBBS. Sandwich ELISA showed that GFAP levels of cerebrum in all groups on days 3 and 7 and that of brainstem(including cerebellum) in MAP, NBBS groups on day 1 and 3 were increased. A review of the background, design and results of these experiments are presented in this paper. Our findings indicate that GFAP is a sensitive and specific biomarker of neurotoxicity.otoxicity.