• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.179-183
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• 2008

In the present study, we examined the effects of several therapeutics of Alzheimer's disease, such as donepezil hydrochloride, tacrine and $\alpha$-phenyl-n-tert-butyl nitrone (PBN) on choline efflux from brain to circulating blood. The brain-to-blood efflux of [$^3H$]choline in rats was significantly inhibited by tacrine and PBN. Also the [$^3H$]choline efflux was reduced by tacrine and donepezil hydrochloride in the TR-BBB cells, in vitro the blood-brain barrier (BBB) model. These results suggest that these drugs may influence choline efflux transport from brain to blood and regulate the choline level in brain resulting in the increase of acetylcholine synthesis.

• Herbal Formula Science
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• v.16 no.1
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• pp.117-130
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• 2008

Korean traditional medicine has been used for the treatment of the various diseases based on both oriental medicinal theory and clinical trials. Thus, the prescriptions of Korean traditional medicine would be useful for the development of new therapeutics. This research focuses on the fundamental study in Korean traditional prescriptions for the development of new hepatoprotective agents. We found two prescriptions. Injinho-Tang and Osumogwa-Tang, showed the significant DPPH free radical scavenging and hepatoprotective effect, respectively. It is well-known that free radical scavenging effect is related to the prevention of various pathological events including liver injury. This paper deals with hepatoprotective effects on tacrine-induced cytotoxicity in Hep G2 cells, free radicals scavenging on both DPPH and superoxide of above two prescriptions. Hot water extract of Injinho-Tang did not show the significant hepatoprotective effect on tacrine-induced cytotoxicity in Hep G2 cells, however, it shows the significant scavenging effects for both DPPH and superoxide radicals. On the other hand, all of the hot water extracts of constituent herbal drugs in Injinho-Tang exhibited the promising protective effect on tacrine-induced cytotoxicity in Hep G2 cells. Of these, water extract of Rhei Rhizoma showed the most prominent effect on tacrine-induced cytotoxicity in Hep G2 cells. Bioassay-guided fractionation of Rhei Rhizoma extract has furnished four compounds, and their chemical structures have been identified by comparison of their spectral data with those of literature as chrysophanol (1), emodin (2), 3,5-dihydroxy-4'- methoxystilbene (3), and rhapontigenin (4), respectively. Among the isolated compounds, compounds 2-4 revealed the significant hepatoprotective effect in vitro when their $EC_{50}$ values compare with that of silybin, as a positive control. It also exhibited that emodin possessed the most hepatoprotective effect among these active compounds. In case of Osumogwa-Tang, its hot water extract showed the moderate protective effect on tacrine-induced cytotoxicity in Hep G2 cells. Hot water extract of Chaenomelis Fructus, one of the constituent herbal drug of this prescription, exhibited the significant hepatoprotective effect with $EC_{50}$ value of $7.8{\pm}0.1\;{\mu}g/ml$, however, it showed strong cytotoxicity in Hep G2 cells above the concentration of $25\;{\mu}g/ml$. It was revealed that both hot water extract of Evodiae Fructus and its butanol soluble fraction showed the moderate hepatoprotective effect but concentration-dependent activity in Hep G2 assay system. Two quinolone alkaloids, evocarpine and dihydroevocarpine, also tested for their hepatoprotective effects on tacrine-induced cytotoxicity in Hep G2 cells, however, these two compounds derived from the Evodiae Fructus as the major constituents did not show in vitro hepatoprotective effect. From these results, it would be necessary to further isolation of its hepatoprotective compounds from the butanol soluble fraction of the hot water extract of Evodiae Fructus.

• Toxicological Research
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• v.28 no.3
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• pp.165-172
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• 2012

Raphanus sativus (Cruciferaceae), commonly known as radish is widely available throughout the world. From antiquity it has been used in folk medicine as a natural drug against many toxicants. The present study was designed to evaluate the hepatoprotective activity of radish (Raphanus sativus) enzyme extract (REE) in vitro and in vivo test. The $IC_{50}$ values of REE in human liver derived HepG2 cells was over 5,000 ${\mu}g/ml$ in tested maximum concentration. The effect of REE to protect tacrine-induced cytotoxicity in HepG2 cells was evaluated by MTT assay. REE showed their hepatoprotective activities on tacrine-induced cytotoxicity and the $EC_{50}$ value was 1,250 ${\mu}g/ml$. Silymarin, an antihepatotoxic agent used as a positive control exhibited 59.7% hepatoprotective activity at 100 ${\mu}g/ml$. Moreover, we tested the effect of REE on carbon tetrachloride ($CCl_4$)-induced liver toxicity in rats. REE at dose of 50 and 100 mg/kg and silymarin at dose of 50 mg/kg were orally administered to $CCl_4$-treated rats. The results showed that REE and silymarin significantly reduced the elevated levels of serum enzyme markers induced by $CCl_4$. The biochemical data were supported by evaluation with liver histopathology. These findings suggest that REE, can significantly diminish hepatic damage by toxic agent such as tacrine or $CCl_4$.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.4
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• pp.409-414
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• 2009

The aim of this study was to investigate the ameliorating effects of deer antler extract on the learning and memory impairments induced by the administration of scopolamine (2 mg/kg, i.p.) in rats. Tacrine was used as a positive control agent for evaluating the cognition enhancing activity of deer antler extract in scopolamine-induced amnesia models. The results showed that the deer antler extract-treated group (200 mg/kg, p.o.) and the tacrine-treated group (10 mg/kg, p.o.) significantly ameliorated scopolamine-induced amnesia based on the Morris water maze test. Although there was no statistical significance of brain ACh contents among the experimental groups, the brain ACh contents of the deer antler extract-treated group was slightly higher than that of the scopolamine-treated group. The inhibitory effect of deer antler extract on the acetylcholinesterase activity in the brain was significantly lower than that of scopolamine-treated group. The tacrine- and the deer antler-treated groups reduced the MAO-B activity compared to the scopolamine-treated group, but not significantly. These results suggest that the deer antler extract could be an effective agent for the prevention of the cognitive impairment induced by cholinergic dysfunction.

• Korean Journal of Pharmacognosy
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• v.38 no.2 s.149
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• pp.176-180
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• 2007

Five liglans, sauchinone (1), di-0-methyltetrahydrofuriguaiacin B (2), manassantin A (3), manassantin B (4) and saucerneol B (5), have been isolated from the MeOH extract of Saururus chinesis roots. The evaluation for protective effect of compounds 1-5 against tacrine-induced cytotoxicity in human liver-derived Hep G2 cells was conducted. Compounds 1,2, and 5 showed significant protective effects with the EC$_{50}$ values of74.2${\pm}$0.9, 111.3${\pm}$0.8,64.3${\pm}$0.8 ${\mu}$M, respectively. Silybin, one of the well-known hepatoprotective agents, used as a positive control, and also showed protective effect with an EC$_{50}$ value of 86.2${\pm}$0.5 ${\mu}$M.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.5
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• pp.1282-1284
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• 2006

In the course of search for hepatoprotective agents from oriental traditional medicines, one compound was isolated from the MeOH extract of the fruits of Schizandra chinensis, and its structure was determined as gomisin J(1). The evaluation for hepatoprotective activity of isolated compound 1 on drug-induced cytotoxicity was conducted, and compound 1 showed protective effect with an EC$_{50}$value of 86.0 ${\pm}$ 5.3 ${\mu}$M against tacrine-induced cytotoxicity in Hep G2 cells. One of the well-known hepatoprotective agents, silybin, used as a positive control, and the hepatoprotective effect of compound 1 is similar with that of silybin (EC$_{50}$ value = 90.5 ${\pm}$ 9.8 ${\mu}$M).

• 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.

• Archives of Pharmacal Research
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• v.28 no.4
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• pp.443-450
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• 2005

In the present study, we have characterized the choline transport system and examined the influence of various amine drugs on the choline transporter using a conditionally immortalized rat brain capillary endothelial cell line (TR-BBB) in vitro. The cell-to-medium (C/M) ratio of $[^3{H}]choline$ in TR-BBB cells increased time-dependently. The initial uptake rate of $[^3{H}]choline$ was concentration-dependent with a Michaelis-Menten value, $K_{m}$, of $26.2\pm2.7{\mu}M$. The $[^3{H}]choline$ uptake into TR-BBB was $Na^{+}-independent$, but was membrane potential-dependent. The $[^3{H}]choline$ uptake was susceptible to inhibition by hemicholinium-3, and tetraethy-lammonium (TEA), which are organic cation transporter substrates. Also, the uptake of $[^3{H}]choline$ was competitively inhibited with $K_{i}$ values of $274 {\mu}M, 251 {\mu}M and 180 {\mu}M$ in the presence of donepezil hydrochloride, tacrine and $\alpha-phenyl-n-tert-butyl nitrone$ (PBN), respectively. These characteristics of choline transport are consistent with those of the organic cation transporter (OCT). OCT2 mRNA was expressed in TR-BBB cells, while the expression of OCT3 or choline transporter (CHT) was not detected. Accordingly, these results suggest that OCT2 is a candidate for choline transport at the BBB and may influence the BBB permeability of amine drugs.

• The Journal of Korean Physical Therapy
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• v.26 no.6
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• pp.436-441
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• 2014

Purpose: The objective of this study was to offer clinical primary data that it's aims to examine effects of transcranial direct current stimulation (tDCS) on cognitive function and biochemical change of rat with alzheimer's disease(AD) induced by injecting scopolamine. Methods: Subjects were instructed cognitive dysfunction model, rat of Sprague-Dawley system was injected with scopolamine and each experimental group was classified into three; group I (n=16) is non-treatment groups; group II (n=16) is applied with the tacrine; group III (n=16) is applied with the tDCS. The ziggurat task test was conducted to observe behavioral changes and cognitive function ability and 7, 14, 21, 28 days after the model. Acetylcholine Esterase (Ach E) activity was examined for biochemical assessment of which the results are followed. Results: Participants showed as to behavioral change, tacrine application group was the most significantly responded, following tDCS application group. As to biochemical change, same as above, tacrine application group was the most significantly responded, following tDCS application group. Conclusion: From these results, confirm that tDCS application to rat with alzheimer's disease leads to positive effects on behavioral, cognitive function changes, and biochemical changes, lasting for certain period of time. This study, in particular, tDCS, which can change excitability of brain cells non-invasively, could provide basic data that is useful as a new treatment way for the patients with cognitive dysfunction.

• Journal of Oriental Neuropsychiatry
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• v.29 no.4
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• pp.207-221
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• 2018

Objectives: The objective of this study was to observe the anti-amnesic effects of Yukmijihwang-tang (YMJHT), on the scopolamine (Sco)-induced memory impairment in C57BL/6 mice through its favorable acetylcholine (ACh). Also, to observe acetylcholinesterase (AChE) activity, Choline acetyltransferase (ChAT) mRNA expressions, and antioxidant effect. Methods: Six groups, with a total of 20 normal and 100 Sco treated mice were selected based on their body weights after 1 week of acclimatization, were used in this study as follows. Half of the mice in each group were used for passive avoidance task tests and hippocampus ACh content, AChE activity and ChAT mRNA expression measurement, and the remaining half in each group used for Morris water maze test and measurement of cerebral antioxidant defense system. Results: Amnesia due to AChE activations and destroyed cerebral cortex antioxidant defense systems were markedly and dose-dependently inhibited after 28 days of continuous oral pre-treatment with YMJHT 400, 200 and 100 mg/kg, respectively. The overall effects of YMJHT 400 mg/kg were similar to those of tacrine 10 mg/kg. Conclusions: Based on the results, it was established that oral administration of YMJHT favorably alleviates Sco-induced memory impairment, through preservation of ACh, mediated by up-regulation of ChAT mRNA expressions and related AChE inhibition and augmentation of cerebral antioxidant defense system, at least in a condition of this experiment. The overall effects of YMJHT 400 mg/kg were similar to those of tacrine 10 mg/kg.