Nyeon-Hyoung An

Wonkwang University, Iksan, North Jeolla, South Korea

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Publications (24)60.34 Total impact

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    ABSTRACT: Using mouse peritoneal macrophages, we have examined the mechanism by which Leonurus sibiricus (LS) regulates nitric oxide (NO) production. When LS was used in combination with recombinant interferon-gamma (rIFN-gamma), there was a marked cooperative induction of NO production; however, LS by itself had no effect on NO production. The increased production of NO from rIFN-gamma plus LS-stimulated cells was almost completely inhibited by pretreatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappaB. Furthermore, treatment of peritoneal macrophages with rIFN-gamma plus LS caused a significant increase in tumor necrosis factor-alpha (TNF-alpha) production. PDTC also decreased the effect of LS on TNF-alpha production significantly. Because NO and TNF-alpha play an important role in immune function and host defense, LS treatment could modulate several aspects of host defense mechanisms as a result of stimulation of the inducible nitric oxide synthase.
    Canadian Journal of Physiology and Pharmacology 11/2008; 86(10):682-90. · 1.56 Impact Factor
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    ABSTRACT: The Scrophularia buergeriana (SB) has long been used to treat various diseases an account of its antimicrobial and anti-virus activity. However, it is unclear how SB regulates the immune responses. This study investigated the effect of SB on the production of cytokines in a human T-cell line, MOLT-4 cells, and mouse peritoneal macrophages. The MOLT-4 cells were cultured for 24 h in the presence or absence of SB plus concanavalin (con) A. SB plus con A significantly increased the level of interleukin (IL)-2, IL-4 and interferon (IFN)-gamma production compared with that of con A alone (approximately 1.79-fold for IL-2, 2-fold for IL-4, and 1.85-fold for IFN-gamma, p < 0.05). SB plus recombinant IFN-gamma (rIFN-gamma) increased the level of IL-12 and NO production compared with rIFN-gamma alone. In addition, SB plus rIFN-gamma increased the level the iNOS expression on mouse peritoneal macrophages. Overall, SB may have an immune-enhancement effect through cytokine production.
    Immunopharmacology and Immunotoxicology 10/2008; 31(2):246-52. · 1.36 Impact Factor
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    ABSTRACT: Epigallocatechin-3-gallate (EGCG) is the major polyphenol component of green tea and is primarily responsible for the green tea effect. EGCG possesses two triphenolic groups in its structure. These groups are reported to be important with respect to anticarcinogenic and antioxidant effects. However, the anti-inflammatory effect of EGCG on Alzheimer's disease (AD) is still not fully understood. In this study, we investigated the effects of EGCG in attenuating the inflammatory response induced by interleukin (IL)-1beta+beta-amyloid (25-35) fragment (Abeta) in human astrocytoma, U373MG cells. EGCG significantly inhibited the IL-1beta+Abeta (25-35)-induced IL-6, IL-8, vascular endothelial growth factor (VEGF) and prostaglandin (PG)E(2) production at 24 h (P<.01). The maximal inhibition rate of IL-6, IL-8, VEGF and PGE(2) production by EGCG was approximately 54.40%, 56.01%, 69.06% and 47.03%, respectively. EGCG also attenuated the expression of cyclooxygenase-2 and activation of nuclear factor-kappaB induced by IL-1beta+Abeta (25-35). We demonstrated that EGCG suppresses IL-1beta+Abeta (25-35)-induced phosphorylation of the mitogen-activated protein kinase p38 and the c-Jun N-terminal kinase. In addition, EGCG induced the expression of mitogen-activated protein kinase phosphatase-1. These results provide new insight into the pharmacological actions of EGCG and its potential therapeutic application to various neurodegenerative diseases such as AD.
    The Journal of Nutritional Biochemistry 09/2007; 18(9):587-96. · 4.55 Impact Factor
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    ABSTRACT: SC-236, (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-]benzenesulfonamide; C(16)H(11)ClF(3)N(3)O(2)S) is a highly selective cyclooxygenase (COX)-2 inhibitor. Recently, there have been reports that SC-236 protects against cartilage damage in addition to reducing inflammation and pain for those with osteoarthritis. However, the mechanism involved in an inflammatory allergic reaction in a murine model has not been examined. The aim of the present study is to elucidate whether and how SC-236 modulates the inflammatory allergic reaction in a murine model. In this study, the anti-allergic effect was investigated using rat peritoneal mast cells, IgE-induced passive cutaneous anaphylaxis (PCA), and the ear-swelling model in mice. Also, we examined the inhibitory effect of SC-236 on the expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. SC-236 was found to inhibit the ear-swelling response and histamine release in the murine model. Additionally, SC-236 was revealed to inhibit the PCA response and COX-2 expression. As a final step, the inhibitory mechanism of SC-236 was shown to occur through phosphorylation of extracellular signal-regulated protein kinase (ERK). These in vitro and in vivo results provide new insight into the pharmacological actions of SC-236 as a potential molecule for therapy for inflammatory allergic diseases.
    Life Sciences 09/2007; 81(11):863-72. · 2.56 Impact Factor
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    ABSTRACT: The Korean indigenous medicine "Dohongsamultang (DHSMT)" has long been used for various cerebrovascular diseases. However, the exact mechanism for the anti-inflammatory effect of DHSMT is not completely understood. The aim of the present study is to elucidate how DHSMT modulates the inflammatory reaction in lipopolysaccaride (LPS)-stimulated peripheral mononuclear cells from cerebral infarction (CI) patients. Production and expression of cytokine was measured via the ELISA and RT-PCR methods. The level of nuclear factor-kappa B (NF-kappaB)/Rel A protein and NF-kappaB DNA binding activity were determined via the Western blot analysis and transcription factor enzyme-linked immunoassay. It showed that DHSMT inhibited the production of TNF-alpha, IL-1beta, and IL-6 induced by LPS in a dose-dependent manner (p < 0.05). The maximal inhibition rates for TNF-alpha, IL-1beta, and IL-6 production by DHSMT were about 50.18%, 32.13%, and 38.03%, respectively. DHSMT inhibited the TNF-alpha mRNA expression in a dose-dependent manner. We also showed that the inhibitory effect of DHSMT is through the suppression of the NF-kappaB pathway. The study suggests an important molecular mechanism by GMGHT to reduce inflammation, which might explain its beneficial effect in the regulation of inflammatory reactions.
    The American Journal of Chinese Medicine 01/2007; 35(3):415-26. · 2.28 Impact Factor
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    ABSTRACT: The Korean genuine medicine "Gigukjiwhangwhangami (GJWGM)" has long been used for various cerebrovascular diseases. However, the exact mechanism that accounts for the anti-inflammatory effect of GJWGM is not completely understood. The aim of the present study is to elucidate how GJWGM modulates the inflammatory reaction in lipopolysaccaride (LPS)-stimulated peripheral mononuclear cells from patients with cerebral infarction. Production of cytokine was measured by the ELISA and RT-PCR method. The level of nuclear factor-kappaB (NF-kappaB)/Rel A protein and NF-kappaB DNA binding activity were determined by the Western blot analysis and TF-EIA method. We showed that GJWGM inhibited the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-6, and IL-8 induced by LPS in dose dependent manner (p<0.05). Maximal inhibition rate of TNF-alpha, IL-1beta, IL-6 and IL-8 production by GJWGM was about 54.34%, 41.37%, 44.04%, and 54.46%, respectively. GJWGM inhibited the TNF-alpha and IL-8 mRNA expression. In addition, we showed that the inhibitory mechanism of GJWGM is through the suppression of NF-kappaB pathway. Our study suggests that an important molecular mechanism by GJWGM reduce inflammation, which may explain its beneficial effect in the regulation of inflammatory reactions.
    Biological & Pharmaceutical Bulletin 11/2006; 29(11):2251-5. · 1.85 Impact Factor
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    ABSTRACT: Interleukin-8 (IL-8) is a potent proinflammatory chemokine that plays an important role in inflammation by activating and recruiting neutrophils, lymphocytes, and eosinophils. To demonstrate the effect of intracellular Ca(2+) on IL-8 production and related signaling, we stimulated human mast cell line HMC-1 with either calcium ionophore A23187 or thapsigargin. Increase of intracellular Ca(2+) resulted in inducing IL-8 gene expression and protein secretion, and addition of EGTA or BAPTA/AM before Ca(2+) stimulation inhibited the induction of IL-8 production. Intracellular Ca(2+) triggered the activation of mitogen-activated protein kinase (MAPK) in HMC-1, especially p42 and p44 isoforms of extracellular signal-regulated kinase (ERK) and p38 MAPK, but not c-Jun N-terminal kinase (JNK). Pretreatment of MAPK inhibitors (PD98059 and SB203580) markedly blocked Ca(2+)-induced IL-8 production from cells, and anti-inflammatory drugs, such as dexamethasone and cyclosporin A, partially inhibited the activation of ERK1/2. We determined that increased Ca(2+) activates the nuclear translocation of the transcription factor NF-kappaB. NF-kappaB inhibitors blocked the ability of Ca(2+) to induce IL-8 production, and the activation of NF-kappaB was required for intracellular Ca(2+)-induced up-regulation of IL-8. These results suggest that increased intracellular Ca(2+) stimulated p38 and ERK1/2 MAPK signaling cascades result in NF-kappaB activation and IL-8 production in HMC-1 cells. This study is the first to identify the intracellular signaling pathways involved in the Ca(2+)-mediated up-regulation of IL-8 synthesis and release from HMC-1 cells.
    Cytokine 01/2006; 32(5):226-33. · 2.52 Impact Factor
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    ABSTRACT: Buchang-tang (BCT) has been known to suppress inflammatory and autoimmune responses. Accordingly, BCT has been clinically used in Korea as an immunomodulatory oriental medicine. Here, we report on the mechanism of action of BCT in activated MOLT-4 cells by determining the affected signaling pathways. BCT inhibits extracellular signal-regulated kinases (ERK)l/2 and p38 activation but does not interfere with phosphorylation of other mitogen-activated protein kinases, c-Jun NH2-terminal kinases 1/2 in MOLT-4 cells. The nuclear localization of nuclear factor of activated T cells 2 (NFATc) was blocked by BCT. Also, degradation of inhibitor kappaB-alpha and transactivation by nuclear factor-kappa B (NF-kappaB)/Rel A were impaired. Furthermore, interlukin (IL)-2 mRNA and protein levels were significantly diminished by BCT treatment. Our data indicate that BCT inhibits ERK1/2, p38 activation, nuclear translocation of NFATc, and NF-kappaB, resulting in diminished secretion of IL-2.
    Journal of Ethnopharmacology 11/2005; 102(1):95-101. · 2.94 Impact Factor
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    ABSTRACT: In the present study, we sought to investigate the signal transduction pathways of expression of cytokines in the ethanol-stimulated human mast cell line, HMC-1. Ethanol significantly increased the intracellular calcium level in HMC-1. Ethanol also significantly enhanced IL-6, TNF-alpha, and TGF-beta1 production compared with media control, but did not significantly affect the IL-1beta production. After 8 h of stimulation, ethanol increased mRNA and protein expression levels of TNF-alpha and TGF-beta1 in HMC-1. The increased cytokine level was significantly inhibited by BAPTA-AM, PD98059, and SB203580. These inhibitors also inhibited ethanol-induced ERK and p38 MAPK phosphorylation. Ethanol resulted in a great increase in protein levels and promoter activity driving luciferase expression of HIF-1alpha and NF-kappaB in HMC-1 cells, but it did not affect on HIF-1alpha mRNA expression. Our observations show that calcium, MAPK activation, HIF-1alpha, and NF-kappaB are necessary for ethanol-induced TNF-alpha and TGF-beta1 expression. These results may have important implications for the study of alcohol-related diseases.
    Life Sciences 10/2005; 77(17):2179-92. · 2.56 Impact Factor
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    ABSTRACT: Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The iron-chelator desferrioxamine (DFX) increased the expression of hypoxia-inducible factor (HIF)-1alpha in the hair cell line, HEI-OC1. The increased VEGF production by DFX was inhibited by iron. DFX also induced the activation of mitogen-activated protein kinase (MAPK) on HEI-OC1. The increased VEGF production by DFX was inhibited by a specific inhibitor of MAPK. In addition, DFX induced the VEGF production and HIF-1alpha stabilization in vivo. These results indicate that VEGF production is regulated via MAPK and HIF-1alpha under hypoxic condition in the inner ear.
    Journal of Neuroimmunology 07/2005; 163(1-2):84-91. · 3.03 Impact Factor
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    ABSTRACT: Iridology is the study of the iris of the eye to detect the conditions of the body and its organs, genetic strengths and weaknesses, etc. Although iridology is not widely used as a scientific tool for healthcare professionals to get to the source of people's health conditions, it has been used as a supplementary source to help the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris among some Korean Oriental medical doctors. Angiotensin converting enzyme (ACE) gene polymorphism is one of the most well studied genetic markers of vascular disease. We investigated the relationship between iridological constitution and ACE polymorphism in hypertensives. We classified 87 hypertensives and 79 controls according to iris constitution and determined the ACE genotype of each individual. DD genotype was more prevalent in patients with a neurogenic constitution than in controls. This finding supports the hypothesis that D allele is a candidate gene for hypertension and demonstrates the association among ACE genotype, Korean hypertensives and iris constitution.
    The American Journal of Chinese Medicine 02/2005; 33(3):501-5. · 2.28 Impact Factor
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    ABSTRACT: In the present study, we investigated the signal transduction pathways of expression of IL-6 in the desferrioxamine (DFX)-stimulated cochlear auditory cell line, HEI-OC1 cells. DFX increased the expression of HIF-1alpha and NF-kappaB in HEI-OC1 cells. DFX significantly increased the production of IL-6 (P<0.05) and expression of IL-6 mRNA but did not affect TNF-alpha production. DFX also induced the activation of mitogen-activated protein kinase (MAPK) including p38, ERK, and JNK on HEI-OC1. Increased IL-6 by DFX was significantly inhibited by p38 inhibitor, SB203580 (about 72% inhibition, P=0.027) but not ERK inhibitor, PD98059 or JNK inhibitor, SP600125. SB203580 inhibited the expression of IL-6 mRNA. Increased IL-6 production was partially inhibited by treatment of iron (HIF-1 inhibitor) or pyrriolidine-dithiocarbamate (PDTC, NF-kappaB inhibitor). DFX also induced IL-6 production and HIF-1alpha expression in the inner ear. We demonstrated the regulatory effects of MAPK, HIF-1alpha, and NF-kappaB on DFX-induced IL-6 production in a HEI-OC1 for the first time. In conclusion, these data indicate that regulation of inflammatory cytokine IL-6 by DFX, through mimicking hypoxic conditions, might explain its beneficial effect in the treatment of hypoxia-induced inner ear diseases.
    Hearing Research 01/2005; 207:59-67. · 2.85 Impact Factor
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    ABSTRACT: Dosiinpartner (DSP) is a newly developed dietary functional food to help control weight. The aim of this study was to evaluate whether DSP combined with a high-fat (HF) diet could influence body weight, fat accumulation, and plasma glucose levels. Mice were fed for 8 weeks with normal diet, HF diet, and HF+10% or 20% DSP diet. Body weight was recorded at 1 week, and plasma levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and glucose were analyzed at the end of the study. Weight increases in the 10% or 20% DSP group were significantly less than in the HF diet group (p<0.05). Plasma total cholesterol and LDL cholesterol levels decreased by 48.3% and 26.8% in the 10% DSP group and by 42.9% and 34.9% in the 20% DSP group, respectively. However, the HDL cholesterol level was unchanged. Glucose levels also decreased by 80.6% in the 10% DSP group but was almost the same in the HF and 20% DSP groups. Our findings indicate that DSP may be beneficial in the regulation of high-fat diet-induced overweight and other complications such as circulatory disorders and diabetes mellitus.
    Biological & Pharmaceutical Bulletin 08/2004; 27(8):1297-300. · 1.85 Impact Factor
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    ABSTRACT: We investigated the effect of disodium cromoglycate (DSCG) on mast cell-mediated immediate-type hypersensitivity. DSCG inhibited systemic allergic reaction induced by compound 48/80 dose-dependently. Passive cutaneous anaphylaxis was inhibited by 71.6% by oral administration of DSCG (1 g/kg). When DSCG was pretreated at concentration rang from 0.01-1000 g/kg, the serum histamine levels were reduced in a dose dependent manner. DSCG also significantly inhibited histamine release from rat peritoneal mast cell (RPMC) by compound 48/80. We confirmed that DSCG inhibited compound 48/80-induced degranulation of RPMC by alcian blue/nuclear fast red staining. In addition, DSCG showed a significant inhibitory effect on anti-dinitrophenyl IgE-mediated tumor necrosis factor-alpha production. These results indicate that DSCG inhibits mast cell-mediated immediate-type allergic reaction.
    Life Sciences 05/2004; 74(23):2877-87. · 2.56 Impact Factor
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    ABSTRACT: Kuibitang (KBT) is clinically used to treat patients suffering from chronic fatigue syndrome (CFS) in South Korea. However, its effect has not been investigated experimentally. Recent reports have shown that CFS patients display an altered cytokine production. We examined the effect of KBT on lipopolysaccharide (LPS)-induced various cytokines production in peripheral blood mononuclear cells (PBMC) of CFS patients and healthy controls. KBT (1 mg/ml) significantly inhibited LPS-induced tumor necrosis factor-alpha, interleukin-10, and transforming growth factor-beta1 production in PBMC of CFS patients. However, LPS-induced interferon-gamma production was significantly increased by KBT (0.01 mg/ml). These results provide evidence of a novel activity of the KBT that regulate cytokines production related with CFS.
    Journal of Ethnopharmacology 03/2004; 90(2-3):253-9. · 2.94 Impact Factor
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    ABSTRACT: Sasang constitutional medicine is a major branch of Korean traditional oriental medicine. Constitutions of Sasang medicine refer to Taeyangin, Taeumin, Soyangin, and Soumin. The differences of disease severity to be shown in the constitution may be due to genetic factors. Therefore, we examined interrelationship among cerebral infarction, CI, angiotensin converting enzyme (ACE) gene polymorphism, and Sasang constitutional classification. We investigated the association between ACE genotype and CI by case-control study in a Korean population. We also classified CI patients and control group into groups according to Sasang constitutional medicine. 208 CI patients and 643 controls without CI were examined. ACE genotype was determined by 7.5 % polyacrylamide gel separation after DNA amplification. The ACE/DD genotype was not associated with CI. The frequency of Taeumin of Sasang constitutional medicine in patients with CI was significantly higher than that in controls (χ2=41.202, p<0.001). However, the Taeumin constitution did not enhance the relative risk for CI in the subjects with ACE/DD genotype. Although we did not find any association between ACE gene polymorphism and CI in Koreans, there were significant differences in allele frequencies between Koreans and Europeans, but not Japanese and Chinese populations. Furthermore, we first attempted to evaluate the efficacy of Sasang constitutional medicine, and to find an association with CI.
    Hereditas 10/2003; 138(3):166 - 171. · 0.96 Impact Factor
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    ABSTRACT: Nicotine is a major pharmacologically active component of cigarette smoke. Excessive cigarette smoking is harmful to lung. Sejin-Eum (SJE) I is composed of various Oriental medicines, and SJE II is SJE I plus seeds of Avena sativa (Gramineae) that reduces the craving for cigarette in man. In this study, we have examined whether an aqueous extract of SJE I/II inhibits nicotine- or cigarette extract (CE)-induced cytotoxicity in human embryonic lung fibroblast, MRC-9. Assessment of cell viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay indicated that SJE I/II (500 and 1000 microg/ml) not only inhibited nicotine-induced cytotoxicity but also had significantly proliferous effect on MRC-9. However, SJE I/II had little effect on inhibition of CE-induced cytotoxicity. These results suggest the possibility that the use of SJE I/II may be useful for improvement of many symptoms by nicotine.
    Journal of Ethnopharmacology 06/2003; 86(1):15-20. · 2.94 Impact Factor
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    ABSTRACT: Ischemic cerebrovascular disease (ICVD) is a multifactorial disease caused by the interactions of several genetic and environmental factors. Tobacco smoke is a major cause of both cancer and vascular disease. Although its carcinogenic role via induction of DNA damage and mutation is well established, the mechanisms involved in vascular disease remain unclear. One possibility is that DNA damage causes smooth muscle cell proliferation in the intima of arteries, thereby contributing to atherothrombotic processes. The binding of chemicals to DNAis modulated by detoxification enzymes, including glutathione S-transferase (GST). We examined whether polymorphisms in this gene, as well as the angiotensin-converting enzyme (ACE) gene influence the risk of ICVD on smoking status. DNA was analyzed for deletions in the GST M1, T1, and ACE genes by polymerase chain reaction (PCR). No significant association was observed between GST null genotype and ICVD, even in smokers. However, a significant association between ACE and ICVD was observed only in smokers (chi(2) = 0.023, p < 0.05). We conclude that GST polymorphism is not a risk factor for the development of ICVD through smoking and suggest a high probability that ACE polymorphism may contribute to the odds of ICVD in smokers.
    Journal of Molecular Neuroscience 02/2003; 20(1):31-8. · 2.89 Impact Factor
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    ABSTRACT: The renin-angiotensin system (RAS) plays a role in the pathogenesis of metabolic diseases. This system was recently found to be completely expressed in human adipose tissue. Especially angiotensin II, the active component of RAS, may affect adipogenesis and adipocyte metabolism. We examined whether obese and non-obese subjects differ from angiotensin-converting enzyme (ACE) genotype distribution, and whether the ACE genotypes affect the anthropometric parameters or the degrees of body mass index (BMI). The study included 155 obese healthy women (BMI > or = 25 kg/m(2), range 25-54.7, age range 15-40 years), 82 non-obese women (BMI < 25 kg/m(2), range 15-40 years), and 613 random controls. Total fat mass and percent body fat (PBF) were determined by dual-energy X-ray absorptiometry (DEXA). Genomic DNA was extracted and used for polymerase chain reaction (PCR)-based genotyping of ACE. Age, percent body fat, waist-to-hip ratio (WHR), body mass index, and cholesterol concentrations did not differ from ACE genotype. No differences were observed for allelic and genotype frequencies between obese women (BMI > or = 25) and 82 non-obese women or 613 random controls. In addition, no association of ACE polymorphism was observed with BMI for genotype in obese women. ACE polymorphism is not a significant factor for BMI and does not contribute to the odds of obesity in obese healthy women from Korea.
    Clinica Chimica Acta 02/2003; 328(1-2):173-8. · 2.85 Impact Factor
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    ABSTRACT: Sasang constitutional medicine is a major branch of Korean traditional oriental medicine. Constitutions of Sasang medicine refer to Taeyangin, Taeumin, Soyangin, and Soumin. The differences of disease severity to be shown in the constitution may be due to genetic factors. Therefore, we examined interrelationship among cerebral infarction, CI, angiotensin converting enzyme (ACE) gene polymorphism, and Sasang constitutional classification. We investigated the association between ACE genotype and CI by case-control study in a Korean population. We also classified CI patients and control group into groups according to Sasang constitutional medicine. 208 CI patients and 643 controls without CI were examined. ACE genotype was determined by 7.5 % polyacrylamide gel separation after DNA amplification. The ACE/DD genotype was not associated with CI. The frequency of Taeumin of Sasang constitutional medicine in patients with CI was significantly higher than that in controls (chi2=41.202, p<0.001). However, the Taeumin constitution did not enhance the relative risk for CI in the subjects with ACE/DD genotype. Although we did not find any association between ACE gene polymorphism and CI in Koreans, there were significant differences in allele frequencies between Koreans and Europeans, but not Japanese and Chinese populations. Furthermore, we first attempted to evaluate the efficacy of Sasang constitutional medicine, and to find an association with CI.
    Hereditas 01/2003; 138(3):166-71. · 0.96 Impact Factor

Publication Stats

235 Citations
60.34 Total Impact Points

Institutions

  • 2001–2008
    • Wonkwang University
      • College of Pharmacy
      Iksan, North Jeolla, South Korea
  • 2003–2007
    • Kyung Hee University
      • • College of Oriental Medicine
      • • Institute of Oriental Medicine
      Seoul, Seoul, South Korea
  • 2005
    • Kyung Hee University Medical Center
      Sŏul, Seoul, South Korea