• Title/Summary/Keyword: interleukin 12

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In Vitro and In Vivo Effects of Piceatannol and Resveratrol on Glucose Control and TLR4-NF-κB Pathway (피세아테놀과 레스베라트롤의 혈당조절 및 TLR4-NF-κB 경로 조절 작용)

  • Lee, Hee Jae;Lee, Hae-Jeung;Yang, Soo Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.2
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    • pp.267-272
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    • 2017
  • Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV), which is a polyphenol known to extend lifespan by stimulating sirtuins. The aim of this study was to investigate the effects of PIC and RSV on the toll-like receptor 4 (TLR4)-nuclear factor kappa B ($NF-{\kappa}B$) pathway in mouse hepatocytes and an obese/diabetic KK/HlJ mouse model. AML12 mouse hepatocytes in the absence or presence of palmitic acids (PA) were treated with PIC ($50{\mu}M$) or RSV ($50{\mu}M$). Male KK/HlJ mice at 20 weeks of age were divided into three subgroups as follows: 1) obese and diabetic control (KK), 2) KK_PIC, and 3) KK_RSV. PIC and RSV were administered orally at a dose of 10 mg/kg/d for 4 weeks. Four weeks of PIC and RSV treatment did not affect body weight or food intake in KK mice. Serum fasting blood glucose was significantly reduced in KK_PIC, and 2 h oral glucose tolerance test area under the curve was significantly reduced by PIC and RSV treatment in KK mice. PIC tended to improve homeostasis model assessment of the insulin resistance index (HOMA-IR) and HOMA beta-cells in diabetic KK mice. TLR4 and $NF-{\kappa}B$ were down-regulated by PIC and RSV treatments in hepatocytes in the absence or presence of PA. Insulin receptor, AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma, nucleotide oligomerization domain-like receptor family pyrin domain-containing 3, interleukin-1, and $NF-{\kappa}B$ were altered in PIC-treated livers. Collectively, PIC and RSV inhibited the $TLR4-NF-{\kappa}B$ pathway, and PIC seems to be more effective than RSV in the regulation of analyzed targets, which are involved in insulin signaling and inflammation in vivo.

Clinical Comparison of Low-dose and High-dose Steroid in Pediatric Cardiac Surgery with Cardiopulmonary Bypass

  • Choi Seok-Cheol;Kim Song-Myung;Kim Yang-Weon
    • Biomedical Science Letters
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    • v.12 no.3
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    • pp.289-301
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    • 2006
  • Cardiopulmonary bypass (CPB) for cardiac surgery triggers the production and release of numerous chemotactic substances and cytokines, ensuing systemic inflammatory response that leads to postoperative major organ dysfunction. Traditionally, corticosteroids (steroid) have been administered to patients undergoing cardiac surgery to ward off these detrimental physiologic alterations. However, the majority of the studies have been performed on adult patients with high-dose steroid. We carried out a randomized, prospective, double-blind study to compare the efficacy of low-dose steroid with that of high-dose steroid and to determine the adequate dose of pretreated-steroid for prophylactic effects in pediatric cardiac surgery. Thirty pediatric patients scheduled for elective cardiac surgery were randomly assigned to two groups; fifteen patients received low-dose methylprednisolone (10mg/kg intravenously, n=15, low-dose group) and the others received high-dose methylprednisolone (30mg/kg intravenously, n=15, high-dose group) 1 hour prior to CPB. Arterial blood samples were taken before CPB (Pre-CPB), 10 minutes after start of CPB (CPB-10), and immediately after CPB-end (CPB-OFF) for measuring total leukocyte counts (T-WBC) and diff-counts, platelet counts, interleukin-6 (IL-6), myeloperoxidase (MPO), total antioxidant (TAO), neuron-specific enolase (NSE), troponin I (TNI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) levels. Other parameters such as volumes of urine output, pulmonary index $(PI,\;PaO_2/FiO_2)$, mechanical ventilating period, intensive care unit (ICU)-staying period, postoperative complications (fever, wound problem), postoperative 24 hrs and total volumes in blood loss, and hospitalized days were also assessed. All parameters were compared between two groups. There were no significant differences in T-WBC counts, monocyte fraction, platelet counts, TA levels, NSE levels, creatinine levels, BUN levels, the volumes of total urine output, PI, the incidences of fever and wound problem, postoperative 24hrs- and total-blood loss volumes and ICU-staying period between two groups (P>0.05). At CPB-OFF, neutrophil fraction, MPO level, TNI level, and AST level were higher in the high-dose group than in the low-dose group (P<0.05). IL-6 level at CPB-10 was higher in the high dose-group than in the low-dose group (P<0.05). Furthermore, mechanical ventilating periods and hospitalized days of the high-dose group were significantly longer than those of low-dose group (P<0.05). The high-dose group had significantly low lymphocyte fi-action at CPB-OFF compared with the low-dose group (P<0.001). These findings suggest that pretreatment of high-dose steroid is not superior to that of low-dose steroid regrading its potential benefits in pediatric cardiac surgery. Therefore, the conventional strategy of steroid treatment, high-dose pretreatment, should be modified in the cardiac surgery with CPB. However, further studies must be performed on the larger number of patients in as much as small number of patients in this study.

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Geumeunyoungji-tang Inhibits Serum IgE Level in Mouse Dermatitis Induced by 2,4-dinitrofluorobenzene

  • Phan, Manh Hung;Jeon, Yong Deok;Kim, Min Cheol;Kim, Su Jin;Kim, Dae Seung;Kwon, Dong Yeul;Kim, Seong Hee;No, Seung Il;Kim, Hyun Jeong;Shin, Hyun Ji;Um, Jae Young;Hong, Seung Heon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.28 no.2
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    • pp.217-222
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    • 2014
  • Lonicerae Flos containing formulation, Geumeumyoungji-tang (GYT), is an herbal prescription prepared using 5 different herbal drugs, namely, Lonicerae Flos, Ganoderma, Lactucae Herba, Xanthii Fructus, and Smilacis Rhizoma. This study was focused on the investigation of the pharmacological effects of GYT on allergic reactions. As the first step of the study, GYT was administered BALB/c mice which were sensitized by 2,4-dinitrofluorobenzene (DNFB). As the result GYT ameliorated dermatitis provoked by DNFB. The serum IgE level of the DNFB sensitized-mouse was significantly decreased when GYT was administered. In order to confirm the moderating effect of this prescription on allergic reaction, GYT was pretreated to human mast cells (HMC-1) before they were stimulated by phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI). GYT suppressed secretion of inflammatory cytokines, interleukin (IL)-6 and IL-8, from HMC-1. Additionally, pretreatment of GYT showed regulating effect on COX-2 expression. Collectively, these findings provide insights into the pharmacological actions of GYT as a potential agent for treatment of allergic dermatitis.

Reduction of Intestinal Polyp Formation in Min Mice Fed a High-Fat Diet with Aloe Vera Gel Extract

  • Chihara, Takeshi;Shimpo, Kan;Beppu, Hidehiko;Tomatsu, Akiko;Kaneko, Takaaki;Tanaka, Miyuki;Yamada, Muneo;Abe, Fumiaki;Sonoda, Shigeru
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4435-4440
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    • 2013
  • Aloe vera gel supercritical $CO_2$ extract (AVGE) has been shown to contain five phytosterols, reduce visceral fat accumulation, and influence the metabolism of glucose and lipids in animal model experiments. Recent epidemiologic studies have shown that obesity is an established risk factor for several cancers including colorectal cancer. Therefore, we examined the effects of AVGE on intestinal polyp formation in Apc-deficient Min mice fed a high-fat diet. Male Min mice were divided into normal diet (ND), high fat diet (HFD), low dose AVGE (HFD+LAVGE) and high dose AVGE (HFD+HAVGE) groups. The ND group received AIN-93G diet and the latter 3 groups were given modified high-fat AIN-93G diet (HFD) for 7 weeks. AVGE was suspended in 0.5% carboxymethyl cellulose (CMC) and administered orally to mice in HFD+LAVGE and HFD+HAVGE groups every day (except on Sunday) for 7 weeks at a dose of 3.75 and 12.5 mg/kg body weight, respectively. ND and HFD groups received 0.5% CMC alone. Between weeks 4 and 7, body weights in the HFD and HFD+LAVGE groups were reduced more than those in the ND group. However, body weights were not reduced in the HFD+HAVGE group. Mice were sacrificed at the end of the experiment and their intestines were scored for polyps. No significant differences were observed in either the incidence and multiplicity of intestinal polyps (${\geq}0.5$ mm in a diameter) among the three groups fed HFD. However, when intestinal polyps were categorized by their size into 0.5-1.4, 1.5-2.4, or ${\geq}2.5$ mm, the incidence and multiplicity of large polyps (${\geq}2.5$ mm) in the intestine in the HFD+HAVGE group were significantly lower than those in the HFD group. We measured plasma lipid (triglycerides and total cholesterol) and adipocytokine [interleukin-6 and high molecular weight (HMW) adiponectin] levels as possible indicators of mechanisms of inhibition. The results showed that HMW adiponectin levels in the HFD group were significantly lower than those in the ND group. However, the levels in the HFD+HAVGE group were significantly higher than those in the HFD group. These results indicate that HAVGE reduced large-sized intestinal polyps and ameliorated reduction in plasma HMW adiponectin levels in Min mice fed HFD.

Effects of Solvent-extracted Fractions from Salicornia herbacea on Anti-oxidative Activity and Lipopolysaccharide-induced NO Production in Murine Macrophage RAW264.7 Cells

  • Lee, Whi-Min;Sung, Hye-Jin;Song, Jae-Chan;Cho, Jae-Youl;Park, Hwa-Jin;Kim, Suk;Rhee, Man-Hee
    • Biomedical Science Letters
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    • v.13 no.3
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    • pp.161-168
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    • 2007
  • Salicornia herbacea L. (Chenopodiaceae: S. herbacea) is a salt marsh plant, which has long been prescribed in traditional medicines for the treatment of intestinal ailments, nephropathy, and hepatitis in Oriental countries. In order to elucidate the mechanisms of this herb, we conducted an anti-oxidative activity, the inhibition of nitric oxide (NO) production, and the suppression of the pro-inflammatory cytokine genes, with the solvent-extracts of S. herbacea. We found that both ethyl acetate and n-butanol tractions showed potent anti-oxidative effects in comparison to other fractions using xanthine oxidase assay with $IC_{50}$ values of $66.0{\pm}0.5\;{\mu}g/ml$ and $82.5{\pm}3.8\;{\mu}g/ml$, respectively. In addition, both ethyl acetate and n-butanol fractions showed more electron donating activity (EDA) than other tractions, according to DPPH (2, 2-Diphenyl-lpicrylhydrazyl radical) assay. The EDA of ethyl acetate fraction ($IC_{50}$ values of $117.5{\pm}3.8\;{\mu}g/ml$) is more significant than that of n-butanol fraction ($IC_{50}$ values of $375.0{\pm}12.5\;{\mu}g/ml$). Among potential anti-oxidative tractions, ethyl acetate traction dose-dependently suppressed lipopolysaccharide (LPS, $0.1\;{\mu}g/ml$)-induced nitric oxide (NO) production in RAW264.7 cell, while n-butanol did not. As expected, ethyl acetate fraction suppressed the expression of inducible NO synthase (iNOS) in RAW264.7 cell stimulated by $0.1\;{\mu}g/ml$ of LPS. Moreover, the ethyl acetate traction suppressed the expression of interleukin-1 $(IL)-1{\beta}$ and granulocyte/macrophage colony-stimulating factor (GM-CSF) mRNA in LPS-stimulated RAW264.7 cells. Therefore, these results suggest that S. herbacea may have anti-oxidative and anti-inflammatory activities by modulating radical-induced toxicity and various pro-inflammatory responses.

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Levosulpiride, (S)-(-)-5-Aminosulfonyl-N-[(1-ethyl-2-pyrrolidinyl) methyl]-2-methoxybenzamide, enhances the transduction efficiency of PEP-1-ribosomal protein S3 in vitro and in vivo

  • Ahn, Eun-Hee;Kim, Dae-Won;Kim, Duk-Soo;Woo, Su-Jung;Kim, Hye-Ri;Kim, Joon;Lim, Soon-Sung;Kang, Tae-Cheon;Kim, Dong-Joon;Suk, Ki-Tae;Park, Jin-Seu;Luo, Qiuxiang;Eum, Won-Sik;Hwang, Hyun-Sook;Choi, Soo-Young
    • BMB Reports
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    • v.44 no.5
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    • pp.329-334
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    • 2011
  • Many proteins with poor transduction efficiency were reported to be delivered to cells by fusion with protein transduction domains (PTDs). In this study, we investigated the effect of levosulpiride on the transduction of PEP-1 ribosomal protein S3 (PEP-1-rpS3), and examined its influence on the stimulation of the therapeutic properties of PEP-1-rpS3. PEP-1-rpS3 transduction into HaCaT human keratinocytes and mouse skin was stimulated by levosulpiride in a manner that did not directly affect the cell viability. Following 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice, levosulpiride alone was ineffective in reducing TPA-induced edema and in inhibiting the elevated productions of inflammatory mediators and cytokines, such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1${\beta}$, and tumor necrosis factor-${\alpha}$. Anti-inflammatory activity by PEP-1-rpS3 + levosulpiride was significantly more potent than by PEP-1-rpS3 alone. These results suggest that levosulpiride may be useful for enhancing the therapeutic effect of PEP-1-rpS3 against various inflammatory diseases.

Serum adipokines play different roles in type I and II ketosis

  • Shen, Liuhong;Zhu, Yingkun;Xiao, Jinbang;Qian, Bolin;You, Liuchao;Zhang, Yue;Yu, Shumin;Zong, Xiaolan;Cao, Suizhong
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.12
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    • pp.1930-1939
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    • 2020
  • Objective: This study was conducted to investigate the differences in several serum adipokines in perinatal dairy cows with type I and II ketosis, and the correlations between these adipokines and the two types of ketosis. Methods: Serum adiponectin (ADP), leptin (LEP), resistin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels, and energy balance indicators related to ketosis were measured. Type I and II ketosis were distinguished by serum glucose (Glu) and Y values and the correlations between adipokines in the two types of ketosis were analyzed. Results: β-Hydroxybutyric acid of type I ketosis cows was significantly negatively correlated with insulin (INS) and LEP and had a significant positive correlation with serum ADP. In type II ketosis cows, ADP and LEP were significantly negatively correlated, and INS and resistin were significantly positively correlated. Revised quantitative INS sensitivity check index (RQUICKI) values had a significantly positive correlation with ADP and had a very significant and significant negative correlation with resistin, TNF-α, and IL-6. ADP was significantly negatively correlated with resistin and TNF-α, LEP had a significantly positive correlation with TNF-α, and a significantly positive correlation was shown among resistin, IL-6, and TNF-α. There was also a significant positive correlation between IL-6 and TNF-α. Conclusion: INS, ADP, and LEP might exert biological influences to help the body recover from negative energy balance, whereas resistin, TNF-α, and IL-6 in type II ketosis cows exacerbated INS resistance and inhibited the production and secretion of ADP, weakened INS sensitivity, and liver protection function, and aggravated ketosis.

Effects of Coptidis Rhizoma on the Change of Interleukin-6 and $TNF-{\alpha}$ Level induced by LPS I.C.V. Injection in Mice (황연(黃連)이 Lipopolysaccharide 뇌실 주입으로 유발된 생쥐의 IL-6와 $TNF-{\alpha}$ 변화에 미치는 영향)

  • Sim Eun-Yeong;Yun Jeong-Moon;Lee Tae-Hee
    • Herbal Formula Science
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    • v.12 no.1
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    • pp.209-223
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    • 2004
  • Objective: This study was conducted to investigate the effects of Coptidis Rhizoma on the plasma IL-6 and $TNF-{\alpha}$ level in mice by intracerebroventricular(I.C.V.) injection of Lipopolysaccharide (LPS). Method: 6 mice were assigned to each of the Normal group, the Control group, and the individual Experimental groups. In the Normal group only saline was administered intragastrically, and in the Control group LPS was injected intracerebroventricularly 1 hr after intragastric administration of saline. In the Experimental groups Coptidis Rhizoma(0.5g/kg, 1.0g/kg, 3.0g/kg) was administered intragastrically to mice 1 hr prior to LPS (100ng/mouse) I.C.V. Injection. To measure the plasma IL-6 and $TNF-{\alpha}$ level of mice, their blood samples were collected from retro-orbital venous plexus, immediately centrifuged at $4^{\circ}C$, and plasma was removed and stored frozen at $-83^{\circ}C$ for later determination of plasma IL-6 and $TNF-{\alpha}$. Result: 1. LPS I.C.V. Injection increased plasma IL-6 level significantly in a dose-dependent manner compared with Normal group. (P<0.01) The plasma IL-6 concentration reached a significant maximal level about 1 hr after LPS(100ng/mouse) I.C.V. Injection.(P<0.001) 2. Both the 0.5g/kg(Sample A) and 1.0g/kg(Sample B) groups to which Coptidis Rhizoma was administered intragastrically 1 hr prior to LPS(100ng/mouse) I.C.V. Injection showed insignificant lower plama IL-6 level in 1 hr than Control group(P>0.05), and 3.0g/kg group(Sample C) conversely showed higher plama IL-6 level than Control group. 3. LPS I.C.V. Injection increased plasma $TNF-{\alpha}$ level significantly in a dose-dependent manner compared with Normal group.(P<0.05) The plasma $TNF-{\alpha}$ concentration reached a significant maximal level about 1 hr after LPS(100ng/mouse) I.C.V. Injection.(P<0.001) 4. All Sample groups(0.5g/kg, 1.0g/kg, and 3.0g/kg) to which Coptidis Rhizoma was administered intragastrically with each constituent-dose 1 hr prior to LPS(100ng/mouse) I.C.V. Injection showed significant lower $TNF-{\alpha}$ plama level in 1 hr than Control group.(P<0.001) These data revealed that Coptidis Rhizoma might have anti inflammatory effect by reducing the plasma $TNF-{\alpha}$ level in a dose dependent manner in mice LPS I.C.V. Injection.

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Effects of Aconiti Tuber on the Change of Interleukin-6 and $TNF-{\alpha}$ Level induced by LPS I.C.V. Injection in Mice (부자(附子)가 Lipopolysaccharide의 뇌실 주입으로 유발된 생쥐의 혈중 IL-6와 $TNF-{\alpha}$ 변화에 미치는 영향)

  • Koh Dong-Kyun;Yun Jeong-Moon;Lee Tae-Hee
    • Herbal Formula Science
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    • v.12 no.1
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    • pp.195-208
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    • 2004
  • Objective: This study was conducted to investigate the effects of Aconiti Tuber on the plasma IL-6 and $TNF-{\alpha}$ level in mice stimulated by intracerebroventricular(I.C.V.) Injection of Lipopolysaccharide(LPS). Method: 6 mice were assigned to each of the normal group, the control group, and the experimental group. In the normal group only saline was administered intragastrically, and in the control group LPS was injected intracerebro-ventricularly 1 hr after intragastric administration of saline. In the experimental groups (Aconiti Tuber 0.5g/kg, Aconiti Tuber 1.0g/kg, Aconiti Tuber 3.0g/kg) each sample was administered intragastrically to mice 1 hr prior to the stimulation by LPS I.C.V. Injection. To measure the plasma IL-6 and $TNF-{\alpha}$ level of mice, their blood samples were collected from retro-orbital plexus, immediately centrifuged at $4^{\circ}C$, and plasma was removed and stored frozen at $-83^{\circ}C$ for later determination of plasma IL-6 and $TNF-{\alpha}$. Result : 1. LPS I.C.V. Injection increased plasma IL-6 level significantly in a dose-dependent manner compared with normal group(P<0.01). The plasma IL-6 concentration reached a significant maximal level about 1 hr after LPS I.C.V. Injection(P<0.001). LPS I.C.V. Injection increased plasma $TNF-{\alpha}$ level significantly in a dose-dependent manner(P<0.05). The plasma $TNF-{\alpha}$ concentration reached a significant maximal level about 1 hr after LPS I.C.V. Injection(P<0.001). 2. Sample A group to which Aconiti Tuber(0.5g/kg) was administered intragastrically 1 hr prior to the stimulation by LPS I.C.V. Injection showed insignificant lower plasma IL-6 level in 1 hr than control group(P<0.0635), and sample B group (Aconiti Tuber 1.0g/kg) showed significant lower plasma IL-6 level in 1 hr than control group(P〈0.05), and sample C group (Aconiti Tuber 3.0g/kg) showed significant lower IL-6 plasma level in 1 hr than control group(P<0.01). 3. sample A group to which Aconiti Tuber(0.5g/kg) was administered intragastrically 1 hr prior to the stimulation by LPS I.C.V. Injection showed insignificant lower plasma $TNF-{\alpha}$ level in 1 hr than control group(P>0.05), and Both sample B(1.0g/kg) and sample C(3.0g/kg) groups showed significant lower $TNF-{\alpha}$ plasma level in 1 hr than control group(P<0.01). These data revealed that Aconiti Tuber might have the anti inflammatory effect by reducing the plasma IL-6 and $TNF-{\alpha}$ level in a dose dependent manner in mice LPS I.C.V. Injection.

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Biological Activity of Bamboo Salt

  • Shin, Hye-Young;Na, Ho-Jeong;Moon, Phil-Dong;Seo, Sang-Wan;Shin, Tae-Yong;Hong, Seoung-Heon;Lee, Ki-Nam;Park, Rae-Kil;Kim, Hyung-Min
    • Food Industry And Nutrition
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    • v.9 no.1
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    • pp.36-45
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    • 2004
  • Bamboo salt has been used for the purpose of prevention and treatment of various diseases in Korea. Present study was carried out to ascertain the effects of purple bamboo salt upon anti-allergic effect, anti-inflammatory activity and immune-enhance effect as well. Purple bamboo salt significantly inhibited the ear swelling response and histamine release induced by compound 48/80 in mice and rat peritoneal mast cells. Purple bamboo salt (0.01 ∼ lg/kg) also dose-dependently inhibited the passive cutaneous anaphylaxis by oral administration. Purple bamboo salt (1 mg/mL) in hibited phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-1${\beta}$ and IL-6 secretion, by 67.04${\pm}$0.08%, 68.01${\pm}$1.85%, 69.48${\pm}$0.54%, respectively. In addition, purple bamboo salt inhibited the expression of TNF-${\alpha}$ mRNA in HMC-1 cells. Finally, we investigated the effect of purple bamboo salt in the forced swimming test (FST) and the change of purple bamboo salt-mediated cytokine production from MOLT-4 cells. At the 7th, immobility time was significantly decreased in the purple bamboo salt-administration group (35.4 ${\pm}$5.9 s for 1 g/kg) in comparison with the control group (93.2 ${\pm}$ 15.45). After FST, the content of glucose in the blood serum was increased and the levels of blood urea nitrogen, lactic dehydrogenase was decreased in purple bamboo salt-administration group. However, it had no effect on the elevation of CK and TP level. Purple bamboo salt (1 mg/mL) significantly increased the interferon (IFN)-${\gamma}$ and IL-2 level compared with media control (about 3.7-fold for IFN-${\gamma}$, about 3.5-fold for IL-2, p〈0.05) but did not affect the IL-4.

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