• The Journal of Korean Medicine
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• v.28 no.2 s.70
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• pp.213-223
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• 2007

Objective : Alzheimer's disease (AD) is a geriatric dementia that is widespread in old age. With an aging populace, AD is a looming problem in public health service. Alzheimer's disease is characterized by specific neuronal degeneration in certain areas of the brain. Mutations and abnormal expression of several genes are associated with ${\beta}-amyloid$ deposits and Alzheimer's disease; among them APP, PS1, and PS2, SOD, free radical, ROS. Methods:We studied herbal medicines that have a relationship to brain degeneration. From pre-modern times, although a variety of oriental prescriptions of Aster tataricus have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. Result : Based on morphological observations by phase-contrast microscope, TUNEL assay and MTT in the culture media, $H_20_2-induced$ cell death was significantly inhibited by Aticus. We examined by ROS formation, catalase activity and GSH activity. We studied the protective effect and inhibitory effects of neurotoxicity in $H_20_2-induced$ PC-12 cells by Aticus. Findings from our experiments show that Aticus inhibits apoptosis, which has neurotoxicities and cell damage in PC-12 cells. In addition, treatment with Aticus ($>25{\mu}g/ml$ for 6hrs) partially prevented $H_20_2-induced$ cytotoxicity in PC-12 cells, and induced a protective effect. Conclusion : As the result of this study, in the Aticus group, the apoptosis in the nervous system was inhibited, protected against the degeneration of PC-12 cells by $H_20_2$. Taken together, Aticus exhibited inhibition of $H_20_2-induced$ apoptotic cell death. Aticus was found to induce protective effect on GSH and catalase in PC-12 cells. Based on these findings, Aticus may be beneficial for the treatment of AD.

• Journal of Oriental Neuropsychiatry
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• v.23 no.2
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• pp.99-120
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• 2012

Objectives : The oriental medicine Jangwonhwan, a boiled extract of 12 medicinal herbs/mushrooms, has been prescribed to patients with cognitive dysfunction, as originally described in the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified formula of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushrooms, was shown to reduce the ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model for Alzheimer's disease. The toxicity of LMK02-Jangwonhwan was investigated in SD rats, by a daily oral administration for 13 weeks and NOAEL(No observed adverse effect dose), a definite toxic dose and target organ, as well. Methods : Quality control of the tablet form of LMK02-Jangwonhwan was established by estimating the indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02-Jangwonhwan was investigated in 6 week old, specific pathogen free (SPF), Sprageu-Dawley rats by oral administration. Each test group consisted of 10 male and 10 female rats. The groups received doses of 500, 1,000 or 2,000 mg/kg/day of test substance for 13 weeks. The clinical signs, death rate, body weight, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemistry, organ weight and pathological changes were examined and compared with those of the control group. Results : The 13-week repeated oral treatment doses didn't result in any specific symptoms or death. There were no significant changes in the rat's weight and food consumption. Further, ophthalmic examination, urinalysis, hematological, serum biochemistry test and organ weight revealed no significant differences. Conclusions : The no-observed-adverse-effect level(NOAEL) of LMK02 for male and female Sprague-Dawley rats was determined as 2,000mg/kg/day and the target organ wasn't confirmed. Because no significant adverse effects were observed, the target organ could not be determined.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.6
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• pp.1034-1041
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• 2010

The oriental medicine Jangwonhwan, which is a boiled extract of 12 medicinal herbs/mushroom, has been prescribed for patients with cognitive dysfunction and it is originally from the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified recipe of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushroom, was shown to reduce ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease. The toxicity of LMK02 was investigated in SD rats by oral repeated adminstration for 4 weeks and we tried to determine test does for 13 weeks repeated study. Quality control of tablet form of LMK02 was established by estimating indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02 was investigated in 6 weeks old specific pathogen free (SPF) Sprageu-Dawley rats by oral administration. Each test group were consist of 5 male and 5 female and they received doses of 500, 1,000 and 2,000 mg/kg/day of test substance for 4 weeks. The clinical signs, death rate, body weight, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemistry, organ weight and pathological changes were examined and compared with those of control group. Urinalysis : We observed increase of PRO(p<0.01), SG(p<0.01) in female rats of 1,000 mg/kg/day and 2,000 mg/kg/day(p<0.01). Also, we observed increase of pH and KET in female rats of 1,000 mg/kg/day(p<0.05) and of 2,000 mg/kg/day(p<0.01). WBC in female rats in 1,000 mg/kg/day and 2,000 mg/kg/day were on increase. Hematological test : We observed increase of MCV in male rats of 250 mg/kg/day. (p<0.05) Serum biochemistry test : We found increase of CHO in female rats of 2,000 mg/kg/day(p<0.05). During the experimental period, there were no animals dead or moribund. There were no treatment related changes of general symptom, food and water consumption, organ weight and autopsy According to the results of 4-week repeated dose range finding study, the highest dose was established as 1000 mg/kg for 13-week repeated dose toxicity study and we determined to put 2 more groups by common ratio two.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.3
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• pp.241-246
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• 2007

Purpose: $[^{11}C]6-OH-BTA-1$ ([N-methyl-$^{11}C$]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole, 1), a -amyloid imaging agent for the diagnosis of Alzheimer's disease in PET, can be labeled with higher yield by a simple loop method. During the synthesis of $[^{11}C]1$, we found the formation of by-products in various solvents, e.g., methylethylketone (MEK), cyclohexanone (CHO), diethylketone (DEK), and dimethylformamide (DMF). Materials and Methods: In Automated radiosynthesis module, 1 mg of 4-aminophenyl-6-hydroxybenzothiazole (4) in 100 l of each solvent was reacted with $[^{11}C]methyl$ triflate in HPLC loop at room temperature (RT). The reaction mixture was separated by semi-preparative HPLC. Aliquots eluted at 14.4, 16.3 and 17.6 min were collected and analyzed by analytical HPLC and LC/MS spectrometer. Results: The labeling efficiencies of $[^{11}C]1$ were $86.0{\pm}5.5%$, $59.7{\pm}2.4%$, $29.9{\pm}1.8%$, and $7.6{\pm}0.5%$ in MEK, CHO, DEK and DMF, respectively. The LC/MS spectra of three products eluted at 14.4, 16.3 and 17.6 mins showed m/z peaks at 257.3 (M+1), 257.3 (M+1) and 271.3 (M+1), respectively, indicating their structures as 1, 2-(4'-aminophenyl)-6-methoxybenzothiazole (2) and by-product (3), respectively. Ratios of labeling efficiencies for the three products $([^{11}C]1:[^{11}C]2:[^{11}C]3)$ were $86.0{\pm}5.5%:5.0{\pm}3.4%:1.5{\pm}1.3%$ in MEK, $59.7{\pm}2.4%:4.7{\pm}3.2%:1.3{\pm}0.5%$ in CHO, $9.9{\pm}1.8%:2.0{\pm}0.7%:0.3{\pm}0.1%$ in DEK and $7.6{\pm}0.5%:0.0%:0.0%$ in DMF, respectively. Conclusion: The labeling efficiency of $[^{11}C]1$ was the highest when MEK was used as a reaction solvent. As results of mass spectrometry, 1 and 2 were conformed. 3 was presumed.

• Journal of Mushroom
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• v.9 no.4
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• pp.194-197
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• 2011

The transitivity of Chemical constituents by Pleurotus ostreatus cultivated in different raw sawdusts, which are Acer tegmentosum MAX, Rhus verniciflura, was investigated. The HPLC chromatography patterns on the chemical constituents of P. ostreatus showed the similar chromatography patterns in the different raw sawdusts and control sawdust. The unknown chemical constituents of P. ostreatus cultivated in the mixed medium added 10 %, 20% raw sawdusts, respectively, were increased. But the significance results in the mixed medium added 50% raw sawdusts were not showed. The chromatography patterns of mycelia grown in media added the 80% MeOH extracts of A. tegmentosum and R. verniciflura showed the similar patterns in comparison with control mycelia. In the results, the secondary metabolites of functional media were not degrade and changed to other derivatives compounds by P. ostreatus.

• The Korean Journal of Nuclear Medicine Technology
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• v.20 no.2
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• pp.42-45
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• 2016

Purpose Neuracep is used to other diagnostic evaluations of the brain to estimate beta-amyloid neuritic plaque density in adult patients with cognitive impairment and inspected cognitive impairment. $^{18}F-Florbetaben$ specially has moderate lipophilicity and property of the added ethanol. It is the subject of interest of the patient pain and residual activity after injecting. Our study is effective injection method of the radiopharmaceutical and patient care. So it is for the highest quality image. Materials and Methods Patients were targeted 70 subjects, it was injected mean $259{\pm}74MBq$ to the patients ($^{18}F-FDG$: 20 subjects, $^{18}F-FP-CIT$: 20 subjects, $^{18}F-Florbetaben$: 30 subjects). After injection (reflusing 2 times, reflusing 3 times) using a 3-way set, it measured the residual activity. When injecting $^{18}F-Florbetaben$, we evaluated the effective injection methods(3-way set method and heparin cap method). The average residual activity after the injection was compared using a statistical analysis of SPSS 12.0(ANOVA, t-test analysis). Also, elemental analysis was performed on $^{18}F-Florbetaben$ by GC (Gas Chromatography). Results When reflusing 2 times measured residual activity as follows ($^{18}F-FDG$: 1.48 MBq, $^{18}F-FP-CIT$: 7.4 MBq, $^{18}F-Florbetaben$: 32.6 MBq). And when reflusing 3 times measured residual activity as follows ($^{18}F-FDG$: 1.85 MBq, $^{18}F-FP-CIT$: 3.7 MBq, $^{18}F-Florbetaben$: 36.3 MBq). There was a significant difference when reflusing 2 times(P < 0.05) and reflusing 3 times (P < 0.05). But when reflusing 3 times, there was no significant difference relation FDG and FP-CIT (P > 0.05). $^{18}F-Florbetaben$ Residual activity according to the injection method was a significant difference (P < 0.05). GC analysis results were measured ethanol: 207665 ppm and acceton: 377.4 ppm. Conclusion $^{18}F-Florbetaben$ was high residual activity compared to FDG and FP-CIT. Heparin cap method was effective when $^{18}F-Florbetaben$ was injected. $^{18}F-Florbetaben's$ ethanol component analysis was highly measured. So it is recommended that inject to 6 sec/ml or more in order to reduce the pain.

• Korean Journal of Food Science and Technology
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• v.38 no.3
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• pp.452-455
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• 2006

The in vitro cytoprotective and anti-oxidative effects of ursodeoxycholic acid, a major active compound from bear's gall were investigated in mouse brain microglia. In the present study, we wished to scrutinize the potential role of UDCA as an anti-neurodegenerative agent in neurodegenerative disease such as Alzheimer's disease. This concept was supported by the multiple preliminary studies in which UDCA has an anti-inflammatory effect in microglial cells. In the study, we found that $7.5\;{\mu}g/mL$ UDCA was effective in the protection of cells from $H_2O_2$ damage, a reactive oxygen, and the resuIt was coincided with the anti-apoptotic effect in DAPI staining. Moreover, the metal-catalyzed oxidation study showed that UDCA has antioxidant effect as much as ascorbic acid at $50{\sim}100\;{\mu}g/mL$. In conclusion, these study results suggested that neuro-degenerative diseases such as Alzheimer's disease probably caused by over-expressed beta amyloid peptide in elderly people can be controled by UDCA through an anti-inflammatory, anti-oxidative and anti-apoptotic effect. The evidences showed in the study may be references for more in-depth in vivo and clinical studies for a candidate of anti-neurodegenerative therapy in the near future.