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4 Weeks Repeated Oral Dose Toxicity Studies with LMK02-Jangwonhwan in SD Rats  

Lyu, Yeoung-Su (Department of Neuropsychiatry, College of Oriental Medicine, Wonkwang University)
Kim, Ji-Hwon (Department of Neuropsychiatry, College of Oriental Medicine, Wonkwang University)
Park, Hyun-Je (Herbal Medicines Unit, Yuhan Research Institute)
Yi, Kyung-Hee (Department of Pediatrics, College of Medicine, Wonkwang University, Sanbon Medical Center)
Lee, Jong-Hwa (Department of Pediatrics, College of Medicine, Wonkwang University, Sanbon Medical Center)
Kang, Hyung-Won (Department of Neuropsychiatry, College of Oriental Medicine, Wonkwang University)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.24, no.6, 2010 , pp. 1034-1041 More about this Journal
Abstract
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.
Keywords
oriental medicine; Alzheimer disease; LMK02-Jangwonhwan; toxicity test;
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Times Cited By KSCI : 4  (Citation Analysis)
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