• Title/Summary/Keyword: Anti TNF

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Screening of Useful Plants with Anti-inflammatory and Antioxidant Activity (항염증 및 항산화 활성 보유 유용 식물 탐색)

  • Lee, Seung-Eun;Choi, Jehun;Lee, Jeong-Hoon;Noh, Hyung-Jun;Kim, Geum-Sook;Kim, Jinkyung;Chung, Hae-Young;Kim, Seung-Yu
    • Korean Journal of Plant Resources
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    • v.26 no.4
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    • pp.441-449
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    • 2013
  • This study was conducted to select some useful plants as functional material candidates. A total of 38 plants were preliminarily screened for the anti-inflammatory and antioxidant activities. The preliminarily selected 8 plants were further investigated to verify the in vitro inhibitory effect on inflammation and oxidative stress. Boehmeria platanifolia (root), Carpinus coreana (branch), and Eupatorium japonicum (leaf) inhibited the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Eupatorium japonicum (leaf) suppressed the expression of cyclooxygenase-2 (COX-2), whereas Boehmeria platanifolia (root) and Prunus yedoensis (branch) inhibited the transcription of nuclear factor-kappa B (NF-${\kappa}B$). Treatment with the extracts ($2.5{\sim}20{\mu}g/ml$) of Abutilon theophrasti (leaf, flower/seed) and Hemistepta lyrata (stem) did not show toxicity on RAW 264.7 cell proliferation, but treatment with $2.5{\mu}g/ml$ of Boehmeria platanifolia (root) exhibited cell toxicity. Carpinus coreana (branch) and Prunus yedoensis (branch) showed potent scavenging activities on peroxynitrite. Akebia quinata (flower), Carpinus coreana (branch), and Prunus yedoensis (branch) effectively inhibited reactive oxygen species (ROS). Abutilon theophrasti (leaf), Boehmeria platanifolia (root), Carpinus coreana (branch), and Eupatorium japonicum (leaf) exhibited strong inhibitory capacity with regard to nitric oxide (NO) production. The results suggested that Abutilon theophrasti (leaf) has in vitro anti-inflammatory and antioxidant activities, and that is a useful functional material candidate.

Anti-atherogenic Effect of Green Tea Product through Hypolipidemic and Anti-oxidative Action in Ovariectomized Rats (난소절제 흰쥐에서 녹차가공품의 지질강하와 항산화 작용을 통한 항동맥경화 효과)

  • Cho, Mi-Kyung;Noh, Kyung-Hee;Kim, Jin-Ju;Song, Young-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.10
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    • pp.1263-1270
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    • 2007
  • This study was carried out to investigate the effect of green tea product (GTP) on the risk factors of atherosclerosis in ovariectomized (OVX) rats. Sprague-Dewley female rats (10 weeks) weighing approximately $279{\pm}2g$ were divided into 4 groups: sham operated control group treated with high cholesterol diet (Sham-C), OVX control group treated with high cholesterol diet (OVX-C), OVX-G 5% group treated with high cholesterol containing 5% GTP and OVX-G 20% group treated with high cholesterol diet containing 20% GTP. Serum TG concentrations was lower in OVX-G 20% group than in the OVX-C group, whereas ratio of HDL-cholesterol to total cholesterol (%) was significantly (p<0.05) increased in the 20% GTP supplementation group than in the Sham-C and OVX-C groups. Tumor necrosis $factor-{\alpha}$ levels were significantly (p<0.05) decreased in the OVX-G 20% group. Hepatic TG levels were significantly (p<0.05) lowered in OVX-G 20% group than in the other groups. Glutathione levels and antioxidant enzyme activities including glutathione-reductase and Mn-superoxide dismutase in liver were significantly (p<0.05) higher in the OVX-G 20% group in the OVX-C group. Fecal total cholesterol concentrations were increased in the GTP supplementation groups than in the OVX-C group. From the above results, it is concluded that GTP may reduce the risk of atherosclerosis via hypolipidemic action. Therefore, it may be used to possibly improve the hyperlipemia in menopausal women.

Anti-inflammatory Metabolites of Agrimonia pilosa Ledeb. and Their Mechanism

  • Park, Mi Jin;Ryu, Da Hye;Cho, Jwa Yeoung;Kang, Young-Hwa
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.04a
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    • pp.13-13
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    • 2018
  • The anti-inflammatory (INF) compounds (1-15) were isolated from Agrimonia pilosa Ledeb. (APL) by activity-guided isolation technique. The isolated compounds (1-15) were identified as quercetin-7-O-rhanmoside (1), apigenin-7-O-glycoside (2), kaempferol-7-O-glycoside (3), apigenin-7-O-[6"-(butyl)-glycoside] (4), querceitn (5), kaempferol (6), apigenin (7), apigenin-7-O-[6"-(pentyl)-glycoside] (8), agrimonolide (9), agrimonolide-6-O-glucoside (10), desmethylagrimonolide (11), desmethylagrimonolide-6-O-glucoside (12), luteolin (13), vitexin (14) and isovitexin (15). Flavonoids, compound 2, 3, 11, and 14-15 have been found in APL for the first time. Furthermore, two novel flavone derivatives, compound 4 and 8, have been isolated inceptively in plant. In the no cytotoxicity concentration ranges of $0-20{\mu}M$, nitric oxide (NO) production level of 1-15 was estimated in LPS-treated Raw 264.7 macrophage cells. The flavone aglycones, 7 (apigenin, $IC_{50}=3.69{\pm}0.34{\mu}M$), 13 (luteolin, $IC_{50}=4.62{\pm}0.43{\mu}M$), 6 (kaempferol, $IC_{50}=14.43{\pm}0.23{\mu}M$) and 5 (quercetin, $IC_{50}=19.50{\pm}1.71{\mu}M$), exhibited excellent NO inhibitory (NOI) activity in dose-dependent manner. In the structure activity relationship (SAR) study of apigenin-derivatives (APD), apigenin; Api, apigenin-7-O-glucoside; Api-G, apignenin-7-O-[6"-(butyl)-glycoside]; Api-BG and apignenin-7-O-[6"-(pentyl)-glycoside]; Api-P, from APL on INF activity was investigated. The INF mediators level such as NO, INF-cytokines, NF-KB proteins, iNOS and COX-2 were sharply increased in Raw 264.7 cells by LPS. When pretreatment with APD in INF induced macrophages, NOI activity of Api was most effective than other APD with $IC_{50}$ values of $3.69{\pm}0.77{\mu}M$. And the NOI activity was declined in the following order: Api-BG ($IC_{50}=8.91{\pm}1.18{\mu}M$), Api-PG ($IC_{50}=13.52{\pm}0.85{\mu}M$) and API-G ($IC_{50}=17.30{\pm}0.66{\mu}M$). The NOI activity of two novel compounds, Api-PG and Api-BG were lower than their aglycone; Api, but more effective than Api-G (NOI: Api-PG and Api-BG). And their suppression ability on INF cytokines such as $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 mRNA showed the similar tendency. Therefore, the anti-INF mechanism study of Api-PG and Api-BG on nuclear factor-kappa B ($NF-{\kappa}B$) pathway, representative INF mechanism, was investigated and Api was used as positive control. Api-BF was more effectively prevent the than phosphorylation of $pI{\kappa}B$ kinase (p-IKK) and p65 than Api-PG in Raw 264.7 cells. In contrast, Api-PG and Api-BG were not reduced the phosphorylation of inhibitor of kappa B alpha ($I{\kappa}B{\alpha}$). Moreover, pretreatment with Api-PG and Api-BG, dose-dependently inhibited LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNAs and proteins in macrophage cells, and their expression were correlated with their NOI activity. Therefore, APL can be utilized to health promote agent associated with their AIN metabolites.

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Anti-inflammatory effect of barley leaf ethanol extract in LPS-stimulated RAW264.7 macrophage (LPS로 자극한 RAW264.7 대식세포에서 보리순 에탄올 추출물의 항염증 효과)

  • Kim, Mee-Kyung;Kim, Dae-Yong
    • Food Science and Preservation
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    • v.22 no.5
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    • pp.735-743
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    • 2015
  • This study investigated the anti-inflammatory activity of barley leaf extract in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and hairless mice. Pre-treatment with barley leaf extract significantly inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-II (COX-II) in a dose-dependent manner in LPS-stimulated RAW264.7 cells. Barley leaf extract also significantly inhibited the secretion of inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) were strongly suppressed by barley leaf extract in LPS-stimulated cells. In hairless mice, barley extract significantly decreased the pathological phenotypes of contact dermatitis, such as erythema, edema, and scabs. These results indicate that barley leaf extract has an anti-inflammatory effect and therefore a possible role in the treatment of inflammatory diseases or in functional cosmetics.

Protective effect of lycopene against cytokine-induced β-cell apoptosis in INS-1 cells (라이코펜이 사이토카인에 의해 유도된 베타세포 사멸에 미치는 효과 및 기전 연구)

  • Kim, Kyong;Jang, Se-Eun;Bae, Gong Deuk;Jun, Hee-Sook;Oh, Yoon Sin
    • Journal of Nutrition and Health
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    • v.51 no.6
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    • pp.498-506
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    • 2018
  • Purpose: Lycopene, a carotenoid with anti-oxidant properties, occurs naturally in tomatoes and pink grapefruit. Although the beneficial effects of lycopene on various disorders have been established, little attention has been paid to the possible anti-diabetic effects of lycopene focusing on ${\beta}$-cells. Therefore, this study investigated the potential of lycopene to protect ${\beta}$-cells against apoptosis induced by a cytokine mixture. Methods: For toxicity experiments, the cells were treated with 0.1 ~ 10 nM of lycopene, and the cell viability in INS-1 cells (a rat ${\beta}$-cell line) was measured using a MTT assay. To induce cytokine toxicity, the cells were treated with a cytokine mixture (20 ng/mL of $TNF{\alpha}$ + 20 ng/mL of IL-$1{\beta}$) for 24 h, and the effects of lycopene (0.1 nM) on the cytokine toxicity were measured using the MTT assay. The expression levels of the apoptotic proteins were analyzed by Western blotting, and the level of intracellular reactive oxidative stress (ROS) was monitored using a DCFDA fluorescent probe. The intracellular ATP levels were determined using a luminescence kit, and mRNA expression of the genes coding for anti-oxidative stress response and mitochondrial function were analyzed by quantitative reverse-transcriptase PCR. Results: Exposure of INS-1 cells to 0.1 nM of lycopene increased the cell viability significantly, and protected the cells from cytokine-induced death. Lycopene upregulated the mRNA and protein expression of B-cell lymphoma-2 (Bcl-2) and reduced the expression of the Bcl-2 associated X (Bax) protein. Lycopene inhibited apoptotic signaling via a reduction of the ROS, and this effect correlated with the upregulation of anti-oxidative stress response genes, such as GCLC, NQO1, and HO-1. Lycopene increased the mRNA expression of mitochondrial function-related genes and increased the cellular ATP level. Conclusion: These results suggest that lycopene reduces the level of oxidative stress and improves the mitochondrial function, contributing to the prevention of cytokine-induced ${\beta}$-cell apoptosis. Therefore, lycopene could potentially serve as a preventive and therapeutic agent for the treatment of type 2 diabetes.

Beneficial Effects of Daebong Persimmon against Oxidative Stress, Inflammation, and Immunity in vivo (대봉감의 항산화, 항염증 및 면역증강 효과)

  • Lee, Hee Jae;Lim, So Young;Kang, Min-Gyung;Park, Jeongjin;Chung, Hyun-Jung;Yang, Soo Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.4
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    • pp.491-496
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    • 2015
  • The purpose of this study was to assess the antioxidant, anti-inflammatory, and immuno-enhancing effects of Daebong persimmon (DP) and Bansi (BS) in vivo. Two types of astringent persimmons (DP and BS) were used for this experiment. C57BL/6J mice were assigned to the following groups: 1) lean control, 2) high-fat diet control (HF), 3) A region DP (3% wt/wt) with HF diet (A-DP), 4) B region DP with HF diet (B-DP), 5) C region DP with HF diet (C-DP), 6) D region BS with HF diet (D-BS), and 7) E region BS with HF diet (E-BS). All mice were sacrificed after 4 weeks of treatment, after which blood and tissues were collected. Antioxidant enzyme activities, inflammatory markers, and immune factors were evaluated. DP and BS treatments did not alter food intake or body weight, compared with HF. Administration of B-DP increased catalase activities in serum. Hepatic levels of malondialdehyde, a product of lipid peroxidation, were significantly lower in A-DP mice than in the HF group. A-DP had down-regulatory effects against inflammation induced by high-fat diet feeding, as shown by significant reduction of interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor-${\alpha}$. Additionally, A-DP treatment exerted an immuno-stimulatory effect, as shown by increasing levels of immunoglobulin G. DP treatment improved the level of insulin-like growth factor-1. These results indicate that DP has beneficial health effects on oxidative stress, inflammation, and immunity in vivo.

Role of Immune Response to Type II Collagen in the Pathogenesis of Rheumatoid Arthritis (류마티스 관절염 병인에서 제2형 콜라겐에 대한 면역반응의 역할)

  • Jung, Young Ok;Hong, Seung-Jae;Kim, Ho-Youn
    • IMMUNE NETWORK
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    • v.3 no.1
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    • pp.1-7
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    • 2003
  • Type II collagen (CII), major component of hyaline cartilage, has been considered as an auto-antigen in rheumatoid arthritis (RA). However, the clinical and biological significances with regard to the CII autoimmunity need to be clarified in human RA. The presence of antibodies to CII has been identified in sera, synovial fluid, and cartilage of patients with RA. In our study, the increased titer of IgG anti-CII in sera was well correlated with C-reactive protein, suggesting that this antibody may reflect the inflammatory status of RA. The titer of anti-CII antibodies (anti-CII Abs) tended to be higher in early stages of diseases. In our extending study, among 997 patients with RA, 269 (27.0%) were positive for circulatory IgG antibody to CII, those levels were fluctuated over time. It is hard to assess the significant amount of T cell responses to CII and CII (255~274) in RA. By using a sensitive method of antigen specific mixed lymphocyte culture, we can detect the presence of CII-reactive T cells in peripheral blood mononuclear cells of RA patients. Sixty seven (46.9%) of 143 patients showed positive CII reactive T cell responses to CII or CII (255~274). The frequencies of CII reactive T cells were more prominent in inflamed synovial fluid (SF) than in peripheral blood. These T cells could be clonally expanded after consecutive stimulation of CII with feeding of autologous irradiated antigen presenting cells (APC). Moreover, the production of Th1-related cytokine, such as IFN-${\gamma}$, was strongly up-regulated by CII reactive T cells. These data suggest that T cells responding to CII, which are probably presenting the IFN-${\gamma}$ producing cells, may play an important role in the perpetuation of inflammatory process in RA. To evaluate the effector function of CII reactive T cells, we investigated the effect of CII reactive T cells and fibroblasts-like synoviocytes (FLS) interaction on the production of pro-inflammatory cytokines. When the CII reactive T cells were co-cultured with FLS, the production of IL-15 and TNF-${\alpha}$ from FLS were significantly increased (2 to 3 fold increase) and this increase was clearly presented in accord to the expansion of CII reactive T cells. In addition, the production of IFN-${\gamma}$ and IL-17, T cell derived cytokines, were also increased by the co-incubation of CII reactive T cells with FLS. We also examined the impact of CII reactive T cells on chemokines production. When FLS were co-cultured with CII stimulated T cells, the production of IL-8, MCP-1, and MIP-1${\alpha}$ were significantly enhanced. The increased production of these chemokines was strongly correlated with increase the frequency of CII reactive T cells. Conclusively, immune response to CII was frequently found in RA. Activated T cells in response to CII contributed to increase the production of proinflammatory cytokines and chemokines, which were critical for inflammatory responses in RA. The interaction of CII-reactive T cells with FLS further augmented this phenomenon. Taken together, our recent studies have suggested that autoimmunity to CII could play a crucial role not only in the initiation but amplification/perpetuation of inflammatory process in human RA.

Qualities and Anti-inflammatory Activity of Kyungokgos Sold in Local Markets (국내 시판 경옥고 제품의 품질 특성 및 항염증 활성)

  • Lee, Ka-Soon;Kim, Gwan-Hou;Kim, Hyun-Ho;Seong, Bong-Jae;Kim, Sun-Ick;Han, Seung-Ho;Kang, Eun Ju;Yoo, Yung Choon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.3
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    • pp.335-341
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    • 2013
  • Kyungokgos purchased in local markets in Korea vary in their combination and mixing ratios during processing. This study was investigated qualities of Kyungokgos manufactured traditionally to evaluating its qualities. The general components of Kyungokgos were moisture (18.62~49.78%), ash (0.198~1.211%), protein (0.89~3.58%), lipid (0.16~1.14%) and carbohydrates (47.95~77.08%). The color values of L, a, and b were 26.49~73.87, 16.51~38.64, and 45.41~88.94, respectively. The viscosity was classified into three non-Newtonian type groups: high, medium, and non-dilatant, according to the increase of loop execution times. Three extracts (KOG-1, -7, and -8, in a 30-fold dilution) showed no cytotoxicity toward RAW 264.7 cells, while the extracts of KOG-2, -4, and -5 showed a low cytotoxic effect. KOG-1 and -2 extracts with low cytotoxicity markedly inhibited the production of the inflammatory mediators-nitric oxide (NO) and tumor necrosis factor-alpha (TNF-${\alpha}$) in LPS-stimulated RAW 264.7 cells. These results indicate that KOG-1 and -2 extracts have anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophages.

Anti-inflammation effect of rebaudioside A by inhibition of the MAPK and NF-κB signal pathway in RAW264.7 macrophage (RAW264.7 대식세포에서 MAPK 및 NF-κB 신호전달 억제를 통한 rebaudioside A의 항염 효과)

  • Choi, Da Hee;Cho, Uk Min;Hwang, Hyung Seo
    • Journal of Applied Biological Chemistry
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    • v.61 no.2
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    • pp.205-211
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    • 2018
  • Rebaudioside A is a natural sweetener isolated from Stevia rebaudiana Bertoni, one of the glycosides based on steviol. Recent studies have shown that rebaudioside A inhibits the inflammatory response by inhibiting cytokines secretion such as interleukin-$1{\alpha}/1{\beta}$ in activated RAW264.7 mouse macrophage cells by LPS. However, the inhibitory mechanism of inflammation by rebaudioside A in the presence of LPS has not been fully elucidated. Therefore, in this study, we tried to investigate the anti-inflammatory activity of rebaudioside A at the protein level when RAW264.7 cells were stimulated by LPS. The inducible nitric oxide synthase protein expression level was reduced in the group treated with $250{\mu}M$ rebaudioside A compared to the LPS-treated group. In addition, the mRNA expression level of $NF-{\kappa}B$, which is a representative nuclear transcription factor by inflammatory signal, was also decreased as compared with that of LPS-treated group. In addition, $NF-{\kappa}B$ and inhibitor-${\kappa}B$ ($I-{\kappa}B$) complexes that are known to be dissociated by $I-{\kappa}B$ phosphorylation and ubiquitination were less phosphorylated than LPS treated group in the presence rebaudioside A. Finally, we could find that rebaudioside A was involved in the $NF-{\kappa}B$ pathway through reducing extracellular signal-regulated kinase1/2 phosphorylation in a concentration-dependent manner. These results suggest that rebaudioside A might suppress inflammatory reaction through MAPK and $NF-{\kappa}B$ regulation in LPS-stimulated RAW264.7.

Dietary Brown Seaweed Modulates Nutrient Metabolism, Anti-oxidant System and Immune Response in Broiler Chicks Injected LPS i.p. (사료 중 미역은 복강내 LPS 주입 육계 병아리에서 영양소 대사, 항산화계 및 면역 반응을 조정한다)

  • Park, In-Kyung;Im, Jin-Taek;Choi, Do-Yul;Koh, Tae-Song
    • Journal of Animal Science and Technology
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    • v.50 no.2
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    • pp.185-198
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    • 2008
  • Influences of dietary brown seaweed(BSW) on the nutrient metabolism, anti-oxidant enzyme activity and cell-mediated immune response were studied in broiler chicks activated acute phase response. 72 Hatched male broiler chicks(Ross) were divided into 12 pens, 6 heads per pen, and fed the BSW 0.0% (Basal) or 2.0% diet, respectively, and injected with the Salmonella typhimurium lipopoly saccharide(LPS) for activation of the acute phase response three times at 8, 10 and 12 d of age. During 4 wks of experimental feeding, growth performance of broiler chicks was not affected by dietary BSW and the acute phase response. Compared with control birds, the acute phase response did not affect the daily weight gain in birds fed BSW 2.0% diet, decreased nitrogen balance(NB) or metabolizable energy(ME) utilization per metabolic body size(kg0.75), and enhanced activities of peroxidase or extracellular SOD(EcSOD), tumor necrosis factor-alpha and ovotransferrin in plasma and MnSOD and CuZnSOD in erythrocyte cytosol. Compared to BSW 0.0% diet, 2.0% diet enhanced protein retention(NB) per kg0.75 regardless the acute phase response, did not affect uric acid nitrogen excretion(UAN) per kg0.75 in birds during the acute phase response, decreased(p<0.05) the UAN excretion per kg0.75 in control birds. And BSW 2.0% diet also decreased(p<0.05) plasma peroxide level and erythrocyte peroxidase or MnSOD activity but increased plasma peroxidase and EcSOD activity and interleukin-1 activity secreted from LPS-stimulated PBMC in 4 week broiler chicks.