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Molecular Genetic Analysis of Behcet's Disease in Korean (한국인 베체트 환자의 분자유전학적 연구)

  • Park, Sang-Bum;Nam, Youn-Hyoung;Park, Su-Min;Lee, Sang-Hyun;Ahn, Young-Chang;Cho, Min-Ho;Kim, Jong-Gyu;Choi, Jae-Gu;Kim, Seong-Kyu;Jang, Won-Cheoul
    • Journal of the Korean Chemical Society
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    • v.51 no.6
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    • pp.536-542
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    • 2007
  • Behcet's disease (BD) is a chronic inflammatory disorder, involving several organs. Inflammation in the disease is thought to be mediated by cytokines derived from T-helper type 1 (Th1) lymphocytes. Although the exact pathogenesis for BD is not completely understood, it has been suggested that the disease is triggered in genetically susceptible individuals by environmental factors, such as microbial agents. It is noted that multiple genes, including MHC (major histocompatibility complex) and non-MHC genes, are implicated in the pathogenesis of BD. This study tries to determine whether HLA-B51, IL-18, SLC11A1 and TNF-α polymorphisms are associated with susceptibility to Behcet's disease in Koreans. As a results, HLA-B51 was a genetic factor with the strongest association with BD. But it is still uncertain whether this HLA molecule is directly involved in the pathogenesis of BD. Although the IL-18 gene polymorphisms were not associated with a susceptibility to BD in the Korean population, the patients carrying the GG genotype at position 137 had a higher risk of developing the ocular lesions. This study suggests that the allele 3 and the genotype allele 3 / allele 3 of 5'-promoter (GT)n polymorphism in the SLC11A1 gene may have a protective effect for the development of BD in the Korean population. There were no evidences for genetic association conferred by the TNF-α gene with respect to susceptibility to BD.

Analysis of Quorum Sensing-Related Phenotypes of Pseudomonas aeruginosa Clinical Isolates (녹농균 임상균주의 쿼럼 센싱 관련 표현형 분석)

  • Jung, Kyung-Ju;Choi, Yu-Sang;Ha, Chang-Wan;Shin, Jeong-Hwan;Lee, Joon-Hee
    • Korean Journal of Microbiology
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    • v.46 no.3
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    • pp.240-247
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    • 2010
  • Pseudomonas aeruginosa is a Gram (-) opportunistic human pathogen causing a wide variety of infections on lung, urinary tract, eyes, and burn wound sites and quorum sensing (QS), a cell density-sensing mechanism plays an essential role in Pseudomonas pathogenesis. In order to investigate the importance of QS in the Pseudomonas infections of Korean patients, we isolated 189 clinical strains of P. aeruginosa from the patients in Pusan Paik Hospital, Busan, South Korea. The QS signal production of these clinical isolates was measured by signal diffusion assay on solid media using reporter strains. While most clinical strains (79.4%) produced the QS signals as similar level as a wild type strain, PAO1 did, where LasR, the initial QS signal sensor-regulator was fully activated, a minority of them (4.2%) produced much less QS signals at the level to which LasR failed to respond. Similarly, while 72.5% of the clinical isolates produced QS signals enough to activate QscR, an another QS signal sensor-regulator, some few of them (9%) produced the QS signals at much lower level where QscR was not activated. For further analysis, we selected 74 clinical strains that were obtained from the patients under suspicion of Pseudomonas infection and investigated the total protease activity that is considered important for virulence. Interestingly, significant portion of them showed very low protease activity (44.6%) or no detectable protease activity (12.2%). When the biofilm-forming ability that is considered very important in chronic infection was examined, most isolates showed lower biofilm-forming activity than PAO1. Similarly, significant portion of clinical isolates showed reduced motility (reduced swarming activity in 51.4% and reduced twitching activity in 41.9%), or non-detectable motility (swarming-negative in 28.4% and twitching-negative in 28.4%). Our result showed that the clinical isolates that produced QS signals at the similar level to wild type could have significantly reduced activities in the protease production, biofilm formation, and motility, and some clinical isolates had unique patterns of motility, biofilm formation, and protease production that are not correlated to their QS activity.

Extract from Prunus mume Sieb. et Zucc. Fruit Prevents LPS-induced Homotypic Aggregation of Monocytic THP-1 Cells via Suppression of Nitric Oxide Production and NF-κB Activation (매실 추출물의 산화질소 생성과 NF-κB 활성 조절을 통한 LPS유도성 THP-1 세포 동형성 응집의 억제 효과)

  • Lee, Hye-Rim;Park, Youngsook;Kim, Hyun Jeong;Lee, Aram;Choi, Jihea;Pyee, Jaeho;Park, Heonyong;Kim, Jongmin
    • Journal of Life Science
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    • v.25 no.7
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    • pp.801-809
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    • 2015
  • Homotypic cell adhesion (homotypic aggregation) in activated monocytes plays a central role in physiological and pathological processes including inflammatory responses, differentiation and migration. The extract of the Prunus mume Sieb. et Zucc. fruit (Maesil) has potential benefits to human health; such as anti-viral, anti-microbial, and anti-cancer activities. Indeed, Maesil extract may modulate inflammatory responses via interference with homotypic aggregation in monocytes. In the present study, the molecular mechanisms underpinning the therapeutic efficacy of Maesil extract in inflammatory diseases were investigated. It was found that Maesil extract inhibited homotypic aggregation in lipopolysaccharide (LPS)-activated monocytes. This was mediated by reduction of nitric oxide (NO) production, partly via inhibition of inducible nitric oxide synthase (iNOS) expression in LPS-activated THP-1 cells. It was confirmed that NO inhibition is a key mechanism in Maesil induced blockade of monocyte aggregation through identification of reversal of this inhibitory effect by the NO-producing agent S-nitroso-N-acetyl penicillamine (SNAP). In addition, Maesil extract significantly attenuated LPS-induced IκB-α phosphorylation and NF-κB translocation into the nucleus. In conclusion, Maesil extract exerts anti-inflammatory effects via inhibition of homotypic aggregation of LPS-activated monocytes through mechanisms involving the suppression of NO production and NF-κB activity, suggesting Maesil extract as a potential therapeutic candidate for the prevention and treatment of chronic inflammatory diseases.

Hepatoprotective and Anticancer Activities of Allomyrina dichotoma Larvae (장수풍뎅이 유충의 간보호 효능 및 항암활성)

  • Lee, Ji-Eun;Jo, Da-Eun;Lee, An-Jung;Park, Hye-Kyung;Youn, Kumju;Yun, Eun-Young;Hwang, Jae-Sam;Jun, Mira;Kang, Byoung Heon
    • Journal of Life Science
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    • v.25 no.3
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    • pp.307-316
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    • 2015
  • Beetle larvae have been used as a traditional medicine to treat various human liver diseases. To prove the liver protective function of Allomyrina dichotoma larvae (ADL), we induced liver damage by the intraperitoneal injection of a hepatotoxic reagent, diethylnitrosamine (DEN), to C3H/HeN male mice and orally administered freeze-dried ADL powder. ADL powder lessened DEN-induced hepatotoxicity considering the reduced signs of acute and chronic hepatotoxicities, such as the ALP level in the blood serum, TUNEL-positive hepatocytes, ductural reactions, steatotic hepatocytes, and collagen deposition of the Masson’s trichrome staining. In addition to hepatoprotection, the anti-cancer activity of ADL has been examined. The ADL powder was extracted with ethanol and then fractionated with hexane, ethyl acetate, and water by a solvent partition technique. The ethyl acetate fraction showed cytotoxicity to various cancer cells through induction of apoptosis and necrosis, as well as the perturbed metabolism of the cancer cell to trigger autophagy. Collectively, ADL contains bioactive substances that can protect hepatocytes from toxic chemicals and trigger cell death in cancer cells. Thus, further purification and analyses of ADL fractions could lead to the identification of novel bioactive compounds.

Pro-apoptotic Effects of Platycodin D Isolated from Platycodon grandiflorum in Human Leukemia Cells (도라지 유래 사포닌 platycodin D에 의한 인체 백혈병세포의 apoptosis 유도)

  • Park, Sang Eun;Lee, Su Young;Shin, Dong Yeok;Jeong, Jin-Woo;Jin, Myung Ho;Park, Seon Young;Chung, Yoon Ho;Hwang, Hye Jin;Hong, Sang Hoon;Choi, Yung Hyun
    • Journal of Life Science
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    • v.23 no.3
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    • pp.389-398
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    • 2013
  • Platycodin D is a major constituent of triterpene saponins, which is found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. Several pharmacological effects of this compound have been reported recently, such as anti-inflammation, immunogenicity, anti-adipogenesis, lowered cholesterol, and anti-cancer activity. However, the mechanism by which this action occurs is poorly understood. In this study, we found that platycodin D greatly increased the potential of the anti-proliferative effect in various cancer cell lines. Our data revealed that platycodin D treatment resulted in a time- and concentration-response growth inhibition of U937 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, chromatin condensation, and the accumulation of cells in the sub-G1 phase. Apoptosis induction of U937 cells by platycodin D correlated with an increase in the Bax/Bcl-2 ratio and caused the down-regulation of IAP family members. In addition, platycodin D treatment resulted in proteolytic activation of caspase-3, the concomitant degradation of poly(ADP-ribose) polymerases, and the collapse of the mitochondria membrane potential (${\Delta}{\Psi}_m$). However, the cytotoxic effects induced by platycodin D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrated the important role that caspase-3 played in the observed cytotoxic effect. These findings suggest that platycodin D may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells. These findings also provided important new insights into possible molecular mechanisms of the anti-cancer activity of platycodin D.

The clinical study of Myasthenia Gravis (중증근무력증(重症筋無力症)에 대(對) 임상적(臨床的) 연구(硏究))

  • Chae, Byung-Yoon
    • The Journal of Korean Medicine
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    • v.17 no.1 s.31
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    • pp.190-211
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    • 1996
  • Generally the Myasthenia Gravis is classified into two of hereditary factor and acquement. Aquired Myasthenia Gravis was Quite well known to be caused by the autoimmune mechanism. Not in accurateness, on the hereditary, acetylcholine receptor antibody was to be analyzed very high in their parents and brothers. Also Myasthenia Gravis is a chronic disease characterized by voluntary muscle weakness and fatigue. above all, ocular Myasthenia Gravis is characterized clinically by blepharoptosis and external ophthalmoplegia and to be showed abut 90% cases and so oriental medicine can not but deal with myasthenia gravis at blepharoptosis. Accordinglv 20 out patients with Myasthenia Gravis were clinical study and observation as to the sex, age, progress state of MG, blood type, history, main symptom, liking for warm and cool food and tepidity, state of pulse, treatment of acupuncture and administration of oriental medicine etc. The results were as follows. 1. There was investigaed on the frequency of attack for sex, age, oculus dexter, oculus sinister, oculus uterque. Among the 20 patients, the number of female were 60% with 12 cases and male were 40% with 8 cases, therefore it was the rate of 6 : 4. the patients under 10 ages and 40 ages were 20% with 4 cases, 10 ages and 50 ages were 15% with 3 cases, 20, 30, 60 ages were 10% with 2 cases. And then oculus uterque was 90% with 18 cases, oculus sinister was 10% with 2 cases and oculus dexter were none of them. 2. Stage I were 50% with 10 patients, stage $II_A$ were 30% with 6 patients and stage $II_B$ were 20% with 4 patients, on the clinical stage and too class I were 20% with 4, class II were 45% with 9, class III were 35% with 7, in the functional activity the patients with chest heavy were 15% with 3 and hyperthyroidism were 10% with 2. 3. Hospital which patients had used to before came to this hospital were 10 university hospital and 6 local clinic. 4. The duration of disease was from 3 months to 30 years, the patients suffering between 3 months and within 1 year were 25% with 5 cases, 1-2 years were 30% with 6 cases, therefore within 2 years were 55%. 4-5 years were 15%, over 7 years were appeared less than 10%. 5. In the main symptom, all of patients were appeared to be heavy in opening their eyes the patients with blephroptosis were 70% with 14 cases on the oculus uterque, oculus sinisterf and oculus dexter, there were 20% with 4 eases each other in the oculogyation incomplete. visual failing, ophthalmoxerosis, strabismus etc and indigetion, frequency of urine(feel hurt), mild stools(or diarrea), oversensitiveness etc. but in addition, all of the other were 10%. 6. In the distribution of blood type, 0 types were 45% with 9 cases, A types were 25% with 5 cases, B and AB types were 15% each other. 7. For the rates of patients of liking for warm and cool food or tepidity, patients of liking for warm food possess 45% with 9 cases, and cool food possess 35% with 7 and tepidity possess 20% with 4, and then most of patients liking for warm food were females and cool food were much more males than females. 8. Hyunsae(弦細) were 40% with 8 cases, Buhurl(浮滑) were 20% with 4 cases, Hyunsak(弦數) were 15% with 3 cases, and in addition, the others were 10%, among 7 types of pulses. 9. The patients with less than 1 week were 40% with 8 cases, and there were female most of them and over 4 weeks were 20% and 1-2weeks were 15%, in the duration acupuncture treatment. 10. 15 kinds of prescriptions were administrated with oriental medicine from 1 week to 20weeks 1_2 weeks were 25.71% with 9 cases, 3 weeks were 17.14% with 6 cases and 6 weeks were 11.42% with 4 cases and also Gamibaetaugunbitang(加味培土健脾湯) were 28.57% with 10 cases, Gamijeounyongtang(加味正容湯) were 14.28% with 5 cases, Gamibojoongyigitung (加味補中益氣湯), Gamiyinsamyangyoungtung (加味人蔘養榮湯) were 8.57% with 3 cases each other and also Gamisamgitung (加味蔘?湯), Gamisamuloajatung(加味四物五子湯) Gamigoudungum (加味鉤藤飮), etc were applied.

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A Study of the Additional Toxicity of Mixed Food Additives to Rat (혼합(混合)된 식품첨가물(食品添加物)이 흰쥐의 생리(生理)에 미치는 상승적(相乘的) 독성(毒性) 효과(效果)에 관(關)한 연구(硏究))

  • Chung, Ho-Kwon
    • Applied Biological Chemistry
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    • v.18 no.2
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    • pp.71-97
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    • 1975
  • To improve the food qualities in Korea, two hundred and fourtynine kinds of food additives have been allowed in food processing, of which one hundred and nineteen kinds could be used under the limitted conditions. Hence, in practical uses in food processing, many kinds of them are mixed at random within the permitted amounts for their special purposes. For last several years, many kinds of the food additives were prohibited because they have been proved to be toxic even with the single dose. Until recently a few studies on the toxicity in the mixture of food additives were reported, however, they were shown to be no severe additional effect on the animal. This study was performed to see if any elevation of chronic or subacute toxicity of food additives occur especially when they are mixed with each other, using three kinds of food additives (DHA, AF-2, BHT) most widely used as food preservatives, antiseptics and antioxidants. One hundred and fifty young male rats were taken and divided into ten feeding groups, one first control group (food additives blank), three second control groups (DHA 0.1%, AF-2 0.1%, BHT 0.5%), three mixture groups of low level (mixture of each 60% of two second control level) and three mixture groups of high level (mixture of each 90% of two second control level). As the methods of biological and clinical tests, the change of body weight (growth rate), daily intake of diets, organ to body weight ratio, histopathological findings of organs, hematological observation, liver and kidney function tests were checked three times during the periods of 24 weeks. The following results were obtained. 1. The low level group of DHA, AF-2 mixture and DHA, BHT mixture revealed a little retardation in growth rate than the first control group, however, they were similar to the second controls, while all the mixture groups of high level showed a more remarkable retardation than the first and second controls. 2. Average daily intake of the diets was the same in each group, showing a similar decreasing tendency (70-100g/kg of body weight) in accordance with the growth rate. It was observed that there are no differences in the taste and appetite in each group of rats. 3. Abnormal enlargements of kidney and lung were not seen in all the mixture groups compared with the controls, while a slight hepatomegaly was observed in all mixture groups of low level as in the second controls. Significant differences (almost 1% level) were observed between the high level groups and the first control group. 4. Histopathological effects of the food additives on lung, kidney and liver tissues were found in all mixture group of high level. The less frequencies of the same effects were also seen in the low level groups. 5. The esterified cholesterol to total cholesterol ratio in the mixture groups of high level showed a little lower values, and the activities of serum glutamate oxaloacetate transaminase and alkaline phosphatase decreased almost with significance of 5% level compared with the first control group. The serum A/G ratio in the mixture groups also decreased. The results demonstrated that the liver function was decreased in the mixture groups compared with the controls. 6. In all groups throughout the test period, kidney functions (concentration of protein and creatinine excreated per hour in urine and renal filtration rate) were shown almost as normal as the first control. 7. Average values of hematocrit, erythrocytes and leucocytes in the mixture groups were in the normal ranges as in the controls, which denotes that the production of blood cells in bone marrow were also normal in all groups. With the above results, it is concluded that when the food additives (DHA, AF-2, BHT) were given together to the rats in several combinations even in less amount, they showed more toxic signs than the single doses.

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Reevaluation of Clinical Efficacy of Peripheral Vasodilator: Ethaverine HCl (말초혈관(襪梢血管) 확장제(擴張劑) Ethaverine HCl의 임상효과(臨床效果)의 재평가(再評價))

  • Kim, Yoon-Young;Cho, Young-W.
    • The Korean Journal of Pharmacology
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    • v.11 no.1 s.17
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    • pp.33-38
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    • 1975
  • The clinical efficacy of Ethaverine, a peripheral vasodilator, was studied according to a double-blind, non-cross over method in 29 diabetic patients with peripheral arterial diseases. The clinical improvement was assessed from the history of patients including the incidence and frequency of intermitten claudication. Ethaverine, after 4 weeks of therapy, was not effective in improving clinical symptoms compared to placebo. Ethaverine, however, was an efective vasodilator than placebo. The quality of vasodilation induced by Ethaverine, was similar to that of alcohol. A new clinical method of studying peripheral vasodilator was presented. The clinical symptoms of peripheral vascular arterial disease in the lower extrimities include reduced intensity of palpable pulses, coldness, and discoloration of the skin. Intermittent claudication may be present. Pathologic changes in vessel architecture precede the symptoms, and recognition of impending vascular insufficiency is a determining factor in selecting vasodilating therapy or surgical management. Also, post-operative patients who have chronic peripheral vascular arterial disease may be candidates for subsequent vasodilating therapy. Peripheral vasodilators, according to the series of reports, may be indicated in vasospastic peripheral vascular condition rather than an occlusive vascular disease and the vessel responds best when a relatively large vascular beds are involved rather than a small, capillary beds. Recently, the clinical efficacy of peripheral vasodilators have been challanged by many clinical investigators and clinicians. In this study, we have re-evaluated the efficacy of Ethaverine HCl as peripheral vasodilator in patients with vasospastic peripheral arterial disease. Ethaverine is claimed to be two to four times as potent a spasmolytic agent as papaverine in a variety of laboratory and clinical work.

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Qualitative Analysis of $GeO_2$ in Germanium-Fortified Yeast. (게르마늄강화효모 내의 $GeO_2$ 정성분석)

  • Kim, So-Yeun;Kim, Myoung-Hee;Woo, Hee-Gweon;Kim, Bo-Hye;Sohn, Tsang-Uk;Jung, Jin-Wook;Baek, Dae-Heoun
    • Microbiology and Biotechnology Letters
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    • v.35 no.2
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    • pp.163-172
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    • 2007
  • This study was designed to investigate that inorganic germanium $(GeO_2)$ did not exist in germanium-fortified yeast or obtained to non-detectable value by current analytical methods and equipments. For this purpose, we achieved $GeO_2$ qualitative analysis protocol which could be the scientific basis of the study. Since reddish brown precipitate was formed from the reaction of $GeO_2$ with 1 equiv $NaBH_4$, and dark brown precipitate was also formed from the reaction of $GeO_2$ with 2 equiv $NaBH_4$, $GeO_2$ was qualitatively analyzed by observing these particular colored-precipitates. Because no color change was showed from the reaction between $NaBH_4$ and $SiO_2$, the color change could be caused by charge transfer transition on Ge-O and B binding properties. The reaction between $NaBH_4$ and germanium-fortified yeast did not show any color change and precipitate formation which meant no $GeO_2$ existed in germanium-fortified yeast. The reaction between $NaBH_4$ and supernatant specimen collected from the outside of dialysis membrane (MWCO 1,200 dalton) did not show any color change and precipitate formation. Therefore, we considered that the both germaniums in and outside of the dialysis membrane were organic germaniums. Germanium-fortified yeast which was biosynthesized organic germanium can be applied not only as a new functional material for improving health, prevention and treatment of chronic degenerative diseases including cancers, and the regulation of immune system, but also as a new materials.

Screening for Antioxidative and Antimutagenic Capacities in 7 Common Vegetables Taken by Korean (한국인 상용채소 7종의 항산화능 및 항돌연변이능 검색)

  • 오세인;이미숙
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.8
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    • pp.1344-1350
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    • 2003
  • This study was performed to investigate the antioxidative effect as the inhibition of malondialdehyde (MDA) and bovine serum albumin (BSA) conjugation reaction, inhibition of lipid peroxidation and the scavenging effect on 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical, and antimutagenic capacities as the Ames test in 7 common vegetables taken by Korean for suggestion of prevention and dietetic treatment of chronic diseases and development of antioxidative and antimutagenic functional food. The water fractions of perilla leaves and sedum were most effective in the inhibition of MDA and BSA conjugation reaction showing 62.5% of inhibition rate among 7 vegetables. The inhibition rates of ethanol fractions of sedum and wild water dropwort on the lipid peroxidation were 67.1% and 61.5%, respectively. The ethanol fractions of crown daisy and wild water dropwort showed the most effective results among 7 vegetables in the DPPH radical scavenging capacities showing inhibition rate of 78.8% and 73.6%, respectively. The indirect and direct antimutagenic effects of ethanol extract of 7 vegetables were examined by Ames test using Salmonella typimurium TA98 and TA100. Inhibitory effects of wild water dropwort was superior to the other vegetables on the Ames test. These results suggest that common 7 vegetables taken by Korean are believed to be a possible antioxidative and antimutagenic capacities, although the results were different, more or less, according to the assay method and vegetables used.