• Title/Summary/Keyword: 대사 억제제

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Effects of Vitamin C on Airway Hyperresponsiveness in Heavy Smokers (흡연자의 기도 과민반응에 대한 비타민 C의 효과)

  • Lee, Sang-Gab;Kim, Ki-Ryang;Eim, Jeong-Ook;Kim, Heung-Up;Lee, Sang-Soo;Chung, Lee-Young;Kim, Hwi-Jong;Lee, Jong-Deog;Hwang, Young-Sil
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.723-735
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    • 1998
  • Background : Vitamin C has been reported to have a role in the decrease of airway hyperresponsiveness in animal models. This data is based on some metabolic actions of vitamin C, such as promotion of histamine degradation, producing more $PGE_2$ than $PGF_{2\alpha}$ in cyclooxygenase pathway, decrease of smooth muscle contraction, and acting as reducing agent of oxidant. It has been also known that heavy smokers have lower blood levels of vitamin C than nonsmokers and this deficiency in heavy smokers have been explained by several mechanisms, such as increased oxidation by oxidants and free radicals, increased biosynthesis of catecholamine and serotonin released by nicotine, and inadequate dietary intake. In this study, We attempted to assess effect of vitamin C on bronchial hyperresponsiveness in heavy smokers who have bronchial hyperresponsiveness and role of vitamin C on bronchial hyperresponsiveness. Method: To assess acute effect of vitamin C on airway hyperresponsiveness, blood sample for vitamin C level and spirometry, methacholine challenge test were done in 17 smokers and 8 nonsmokers, and one hour after oral administration of vitamin C 3 g, blood sample for vitamin C level and spirometry, methacholine challenge test were repeated. To assess chronic effect of vitamin C on airway hyperresponsiveness, after daily administration of vitamin C 1 g for one week in 17 smokers, blood sample for vitamin C level and spirometry, methacholine challenge test were done. To assess role of vitamin C, after oral administration of vitamin C 3 g plus indomethacin 100 mg in 12 of 15 smokers who were reactive to methacholine challenge test, spirometry and methacholine challenge test were done and after oral intake of indomethacin 100 mg in 12 smokers who were reactive to methacholine challenge test, spirometry and methacholine challenge test were repeated. Result: There were no significant differences in whole blood vitamin C levels between smokers($1.17{\pm}0.22$ mg/dL) and nonsmcikers($1.14{\pm}0.19$ mg/dL) (p>0.05). Fifteen of the 17 smokers(88.2%) were reactive to methacholine challenge test and 10 of the 15 smokers who were reactive to methacholine challenge test were less than 8 mg/dL in $PC_{20}FEV-2$, and 7 of the 8 nonsmokers(87.5%) were nonreactive to methacholine challenge test There were significant decrease in bronchial responsiveness after oral administration of vitamin C 3 g in 13 of the 15 smokers who were reactive to methacholine challenge test This significant decrease persisted with maintenance daily administration of 1 g for one week. $PC_{20}FEV-2$ were not correlated to vitamin C levels in smokers. After oral administration of indomethacin 100 mg, significant reduction of bronchial responsiveness that occured after oral administration of vitamin C 3 g in smokers were attenuated. Conclusion: Although there were no significant differences in whole blood vitamin C levels between smokers and nonsmokers. heavy smokers have significant increase in bronchial responsiveness than nonsmokers. This bronchial hyperresponsiveness of heavy smokers can be attenuated by vitamin C supplement. Disappearance of vitamin C effect by indomethacin supplement may suggest that vitamin C exert its effect via alteration of arachidonic acid metabolism.

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The Effect of Interferon-γ on Bleomycin Induced Pulmonary Fibrosis in the Rat (Interferon-γ 투여가 쥐에서의 Bleomycin 유도 폐 섬유화에 미치는 영향)

  • Yoon, Hyoung Kyu;Kim, Yong Hyun;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyung;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.1
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    • pp.51-66
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    • 2004
  • Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.

Clinical Study of Topotecan as Second-Line Treatment in Small Cell Lung Cancer (소세포폐암의 2차요법으로서의 Topotecan의 치료효과)

  • Kim, Hak-Ryul;Yang, Sei-Hoon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.3
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    • pp.230-240
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    • 2002
  • Background : The majority of chemotherapy-treated small cell lung cancers(SCLC) patients eventually recur. Although many patients are in excellent physical condition at the time of recurrence, few drugs or drug combinations are capable of effecting a tumor regression in this setting. Topotecan, a topoisomerase I inhibitor, is one of the more widely studied single afents in SCLC. The aim of this study was to determine the response rate, survival and toxicity of topotecan as a second line traeatment SCLC. Materials and Methods : 19 patients with measurable SCLC, progressive during the first line chemotherapy (9 cases) or recurrent after the first line chemotherpy(10 cases), were enrolled in this study. Topotecan was administered as a 30-minute daily infusion at a dose of 1.5mg/$m^2$ for 5 consecutive days, every 3 weeks. Results : The overall response rate was 26.3%(5/19, CR 2, PR 3, SD 3, PD 11). The median survival was 24 weeks. The response rate and survival were poor in the nonresponders during first chemotherapy, those who were refractory to the first chemotherapy(recurrent within 3 months after completion of first chemotherapy) and extensive disease, but the results were not statistically significant. The toxicities were mainly hematologic and anemia grade III 1/90, leukopenia grade III 6/90 IV 4/90, thrombocytopenia grade III 1/90 IV 1/90, vomiting grade III 1/90 of cycles were occurred. There was no treatment-related deaths due to severe myelosuppression. Conclusion : Topotecan can be an active second line chemotherapeutic agent for treating SCLC.

Characterization of Laccase Purified from Korean Pycnoporus cinnabarinus SCH-3 (한국산 주걱송편버섯(Pycnoporus cinnabarinus) SCH-3로부터 정제 된 Laccase의 특성)

  • Park, Eun-Hye;Yoon, Kyung-Ha
    • The Korean Journal of Mycology
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    • v.31 no.2
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    • pp.59-66
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    • 2003
  • Laccase produced by Pycnoporus cinnabarinus SCH-3 isolated from Korea was partially purified using ultrafiltration, anion exchange chromatography and affinity chromatography, The laccase was produced as the predominant extracellular phenoloxidase during primary metabolism. Neither lignin peroxidase nor manganese-dependent peroxidase were detected in the culture fluid. In order to examine the effect of inducers in laccase production, 2,5-xylidine was added in the culture of Pycnoporus cinnabarinus SCH-3. Addition of 2,5-xylidine enhanced 25-fold laccase production. Purified laccase was a single polypeptide having a molecular mass of approximately 66 kDa, as determined by SDS-polyacrylamide gel electrophoresis, and carbohydrate content of 9%. $K_{m}\;and\;V_{max}$ values for laccase with ABTS [2,2-azinobis (3-ethylbenzthiazoline 6-sulfonic acid)] as a substrate (Lineweaver-Burk plot) was determined to be $44.4{\mu}M\;and\;56.0{\mu}mole$, respectively. The optimal pH for laccase activity was found to be 3.0. The enzyme was very stable for 1 hour at $60{\circ}C$. Half-life ($t_{1/2}$) of the enzyme was about 10 min at $80{\circ}C$. Spectroscopic analysis of purified enzyme indicated that the enzyme was typical of copper-containing protein. Substrate specificity and inhibitor studies for laccase also indicated to be a typical fungal laccase. The N-terminal amino acid sequence of the P. cinnabarinus SCH-3 laccase showed 94% of homology to the N-terminal sequences of laccases from P. cinnabarinus PB and P. coccineus.

The neuroprotective effect of mycophenolic acid via anti-apoptosis in perinatal hypoxic-ischemic brain injury (주산기 저산소성 허혈성 뇌손상에서 항세포자멸사를 통한 mycophenolic acid의 신경보호 효과)

  • Kim, Ji Young;Yang, Seung Ho;Cha, Sun Hwa;Kim, Ji Yeun;Jang, Young Chae;Park, Kwan Kyu;Kim, Jin Kyung;Chung, Hai Lee;Seo, Eok Su;Kim, Woo Taek
    • Clinical and Experimental Pediatrics
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    • v.50 no.7
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    • pp.686-693
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    • 2007
  • Purpose : Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a potent inhibitor of inosine-monophosphate dehydrogenase (IMPDH), a new immunosuppressive drug used. It was reported that MPA protected neurons after excitotoxic injury, induced apoptosis in microglial cells. However, the effects of MPA on hypoxic-ischemic (HI) brain injury has not been yet evaluated. Therefore, we examined whether MPA could be neuroprotective in perinatal HI brain injury using Rice-Vannucci model (in vivo) and in rat brain cortical cell culture induced by hypoxia (in vitro). Methods : Cortical cells were cultured using a 18-day-pregnant Sprague-Dawley (SD) rats and incubated in 1% $O_2$ incubator for hypoxia. MPA ($10{\mu}g/mL$) before or after a HI insult was treated. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 hours of hypoxic exposure (8% $O_2$). MPA (10 mg/kg) before or after a HI insult were administrated intraperitoneally. Apoptosis was measured using western blot and real-time PCR for Bcl-2, Bax, caspase-3. Results : H&E stain revealed increased brain volume in the MPA-treated group in vivo animal model of neonatal HI brain injury. Western blot and real-time PCR showed the expression of caspase-3 and Bax/Bcl-2 were decreased in the MPA-treated group In in vitro and in vivo model of perinatal HI brain injury, Conclusion : These results may suggest that the administration of MPA before HI insult could significantly protect against perinatal HI brain injury via anti-apoptotic mechanisms, which offers the possibility of MPA application for the treatment of neonatal HI encephalopathy.

Isotopic Determination of Food Sources of Benthic Invertebrates in Two Different Macroalgal Habitats in the Korean Coasts (동위원소 분석에 의한 동해와 남해 연안의 상이한 해조류 군락에 서식하는 저서무척추동물 먹이원 평가)

  • Kang, Chang-Keun;Choy, Eun-Jung;Song, Haeng-Seop;Park, Hyun-Je;Soe, In-Soo;Jo, Q-Tae;Lee, Kun-Seop
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.12 no.4
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    • pp.380-389
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    • 2007
  • Stable carbon and nitrogen isotopes were analyzed in suspended particulate organic matter, macroalgae and macrobenthic invertebrates in order to determine the importance of primary organic matter sources in supporting food webs of rocky subtidal and intertidal macroalgal beds in the Korean coasts. Investigations were conducted at the inter tidal sites within Gwangyang bay, a semi-enclosed and eutrophicated bay, and the subtidal sites of the east coast, a relatively oligotrophic and open environment, in May and June 2005. Water-column suspension feeders showed more negative $\delta^{13}C$ values than those of the other feeding guilds, indicating trophic linkage with phytoplankton and thereby association with pelagic food chains. In contrast, animals of the other feeding guilds, including interface suspension feeders, herbivores, deposit feeders, omnivores and predators, displayed relatively less negative $\delta^{13}C$ values than those of the water-column suspension feeders and similar with that of macroalgae, indicating exclusive use of macroalgae-derived organic matter and association with benthic food chains. Most the macrobenthic species were considered to form strong trophic links with benthic food chains. In addition, the distribution of higher $\delta^{15}N$ values in macrobenthic consumers and macroalgae at the intertidal sites of Gwangyang Bay than those at the subtidal sites of the east coast suggests that anthropogenic nutrients may enhance the macroalgal production at the intertidal sites and in turn be incorporated into the particular littoral food web in Gwangyag Bay. These results confirm the dominant role of macroalgae in supporting rocky subtidal and intertidal food webs in the Korean coasts.

Effect of Reserpine on the Behavioral Defects, Aβ-42 Deposition and NGF Metabolism in Tg2576 Transgenic Mouse Model for Alzheimer's Disease (알츠하이머질환 모델동물인 Tg2576마우스의 행동, Aβ-42 침적, 신경성장인자 대사에 미치는 reserpine의 영향)

  • Go, Jun;Choi, Sun Il;Kim, Ji Eun;Lee, Young Ju;Kwak, Moon Hwa;Koh, Eun Kyoung;Song, Sung Hwa;Sung, Ji Eun;Hwang, Dae Youn
    • Journal of Life Science
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    • v.23 no.6
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    • pp.812-824
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    • 2013
  • Reserpine, an anti-hypertensive drug, is able to positively modulate several phenotypes associated with $A{\beta}$ toxicity in a Caenorhabditis elegans model of Alzheimer's disease (AD). We investigated into the therapeutic effects of reserpine on mammalian neurodegenerative disorders, and found that significant alteration of the key factors influencing AD was detected in Tg2576 mice after reserpine treatment for 30 days. The aggressive behavior of Tg2576 mice was significantly improved upon reserpine treatment, whereas their social contact was consistently maintained. Furthermore, the levels of $A{\beta}$-42 peptide in the hippocampus of the brain and blood serum were lower in the reserpine-treated group than in the vehicle-treated group. Among g-secretase components, the expression levels of PS-2, Pen-2, and APH-1 were slightly lower in reserpine-treated Tg2576 mice, although a significant change in nicastrin (NCT) expression was not detected. Furthermore, the serum level of nerve growth factor (NGF) increased in reserpine-treated Tg2576 mice compared with vehicle-treated mice. Among down-stream effectors of the NGF receptor TrkA signaling pathway, reserpine treatment induced elevation of TrkA phosphorylation and reduction of ERK phosphorylation. In addition, in the NGF receptor $p75^{NTR}$ signaling pathway, the expression levels of $p75^{NTR}$ and Bcl-2 were enhanced in reserpine-treated Tg2576 mice compared with vehicle-treated mice, whereas the expression level of RhoA declined. Overall, these results suggest that reserpine can help relieve AD pathogenesis in Tg2576 mice through downregulation of $A{\beta}$-42 deposition, alteration of ${\gamma}$-secretase components, and regulation of NGF metabolism.

Effect of Wine Yeast, Temperature and Moisture Contents on Characteristics of Jeung-Pyun Batter (Wine Yeast와 온도 및 수분함량이 증편 반죽의 특성에 미치는 영향)

  • 유진현;한규홍
    • Culinary science and hospitality research
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    • v.8 no.3
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    • pp.309-321
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    • 2002
  • In this study, the characteristics of Jeung-pyun hatter were investigated by wine yeast. The processing conditions were optimized by physicochemical characterization including pH, volume, reduced sugar. The effect of yeast concentration, moisture content on the fermentation time and temperature were investigated in view of improving productivity. It was found that the volume was increased at maximum state when the fermentation was carried out at 35 $^{\circ}C$ with 0.1% yeast concentration 60% of moisture. The quality of Jeung-Pyun was most preferable in the condition of 0.1% wine yeast(Pasteur Red) for 8 hrs at 35$^{\circ}C$.

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Effects of Fermented Soybean Paste Chungkukjang on the Immunoreactivity in Ovariectomized Mice (청국장이 난소적출 마우스의 면역 기능에 미치는 영향)

  • Park, Hyunjin;Yoon, Leena;Kim, Hyun-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.12
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    • pp.1930-1939
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    • 2013
  • It has been reported that Chungkukjang, one of Korean traditional fermented soybean products, may improve hypertension, diabetes, and hyperlipidemia. In this study, we sought to investigate the immunoenhancing effects of Chungkukjang in ovariectomized mice. For the first period, female SLC ddy mice were either sham-operated (Sham; n=27) or ovariectomized (OVX; n=27). As a basal diet, ovariectomized mice were fed low-calcium diet for faster induction of osteoporosis for six weeks, and those in the Sham group were fed AIN-76 diet. For the second period, half of the OVX group (n=9) and the Sham group (n=9) were fed a Chungkukjang-based diet (CKJ); whereas the other half (OVX; n=9/ Sham; n=9) were fed a casein-based diet (CSI) for 8 weeks. After a second period, we collected the blood via heart puncture and measured the splenocytes proliferation, T lymphocyte subsets by flowcytometry, and levels of serum cytokines (IL-2, IL-4, IL-6, IL-10, IFN-${\gamma}$ and TNF-${\alpha}$) by ELISA assay. The OVX+CKJ group showed higher splenocytes proliferation, higher ratio of CD4/CD8, and lower levels of IL-6 and TNF-${\alpha}$ cytokines compared to the OVX+CSI group. The Sham+CKJ group showed cytokine productions, such as higher levels of IL-10 and IFN-${\gamma}$, and lower levels of IL-6 and TNF-${\alpha}$ compared to the Sham+CSI group. The result of this study suggests that Chungkukjang may lower the proinflammatory cytokine levels in both the OVX and Sham groups. In addition, Chungkukjang could make a balance of T cell subset proliferations and enhance the splenocyte proliferations in the OVX group.

Antioxidant Effects and Improvement of Lipid Metabolism of Acanthopanacis cortex Water Extract in Rats Fed High Fat Diet (고지방 식이 흰쥐에서 오가피 추출물의 항산화 효과 및 지질 개선 효과)

  • Park, Young-Sook
    • Journal of the East Asian Society of Dietary Life
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    • v.20 no.1
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    • pp.37-45
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    • 2010
  • The effects of an Acanthopanacis cortex water extract on lipid levels, lipid peroxide, total antioxidant status and antioxidant enzyme activities were evaluated in rats fed one of the following diets for six weeks: normal diet and deionized water (ND), normal diet and Acanthopanacis cortex water extract (NDC), high fat diet and deionized water (HFD), high fat diet and Acanthopanacis cortex water extract (HFDC). The food intakes were significantly lower, but the food efficiency ratios were significantly higher in the high fat diet groups. The level of HDL-cholesterol in the plasma was significantly increased and the levels of LDL-cholesterol and triglyceride in the plasma were significantly decreased by the Acanthopanacis cortex water extract in the high fat diet groups. As a a result, the AI (atherogenic index) and CRF (cardiac risk factor) were significantly lower in the high fat diet groups that were treated with Acanthopanacis cortex water extract. The triglyceride and the total cholesterol of the liver were also significantly upregulated in the high fat diet groups, while the total cholesterol of the liver decreased in response to treatment with Acanthopanacis cortex water extract (HFDC). The plasma and liver concentrations of thiobarbituric acid reactive substances (TBARS) were significantly reduced by the addition of Acanthopanacis cortex water extract to the normal diet groups. The total antioxidant status (TAS) in the plasma was significantly upregulated by adding Acanthopanacis cortex water extract to the high fat diet groups. The activities of SOD, catalase and GST were also significantly higher in the Acanthopanacis cortex water extract groups when compared to the ionized water groups. The activity of GSH-Px and the concentration of GSH in the liver were significantly higher following the addition of Acanthopanacis cortex water extract to the high fat diet groups. Taken together, these results suggest that a supplementation of the diet of rats fed a high fat diet with Acanthopanacis cortex water extract improves lipid metabolism, reduces lipid peroxide and improves the activities of antioxidant enzymes, which may have favorable effects on antioxidant systems by improving the total antioxidant status (TAS).