• Title/Summary/Keyword: liver cytokines

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Effect of combined mulberry leaf and fruit extract on liver and skin cholesterol transporters in high fat diet-induced obese mice

  • Valacchi, Giuseppe;Belmonte, Giuseppe;Miracco, Clelia;Eo, Hyeyoon;Lim, Yunsook
    • Nutrition Research and Practice
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    • v.8 no.1
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    • pp.20-26
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    • 2014
  • Obesity is an epidemic disease characterized by an increased inflammatory state and chronic oxidative stress with high levels of pro-inflammatory cytokines and lipid peroxidation. Moreover, obesity alters cholesterol metabolism with increases in low-density lipoprotein (LDL) cholesterols and triglycerides and decreases in high-density lipoprotein (HDL) cholesterols. It has been shown that mulberry leaf and fruit ameliorated hyperglycemic and hyperlipidemic conditions in obese and diabetic subjects. We hypothesized that supplementation with mulberry leaf combined with mulberry fruit (MLFE) ameliorate cholesterol transfer proteins accompanied by reduction of oxidative stress in the high fat diet induced obesity. Mice were fed control diet (CON) or high fat diet (HF) for 9 weeks. After obesity was induced, the mice were administered either the HF or the HF with combination of equal amount of mulberry leaf and fruit extract (MLFE) at 500mg/kg/day by gavage for 12 weeks. MLFE treatment ameliorated HF induced oxidative stress demonstrated by 4-hydroxynonenal (4-HNE) and modulated the expression of 2 key proteins involved in cholesterol transfer such as scavenger receptor class B type 1 (SR-B1) and ATP-binding cassette transporter A1 (ABCA1) in the HF treated animals. This effect was mainly noted in liver tissue rather than in cutaneous tissue. Collectively, this study demonstrated that MLFE treatment has beneficial effects on the modulation of high fat diet-induced oxidative stress and on the regulation of cholesterol transporters. These results suggest that MLFE might be a beneficial substance for conventional therapies to treat obesity and its complications.

Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice

  • Guo, Qi;Shen, Zhiyang;Yu, Hongxia;Lu, Gaofeng;Yu, Yong;Liu, Xia;Zheng, Pengyuan
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.1
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    • pp.15-23
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    • 2016
  • Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated $I{\kappa}B{\alpha}$ and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.

Studies on the Effect of Corilagin Isolated from Euphorbia helioscopia on Collagen-Induced Arthritis (II);CytokinesAnalysis of Collagen II Induced Arthritis Mice Model (택칠에서 분리한 Corilagin이 Collagen 유발 관절염에 미치는 영향 (II);Corilagin을 투여한 류마티스 관절염 유발 생쥐의 사이토카인 분석)

  • Shin, Sam-Kee;Chang, Jun-Pok;Doh, Eun-Soo
    • Korean Journal of Plant Resources
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    • v.21 no.4
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    • pp.336-340
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    • 2008
  • Corilagin (CRN) isolated from Euphorbia helioscopia as rheumatoid arthritis drug. CRN was medicated to the abdominal cavity of collagen induced arthritis (CIA) mice that was an animal model for rheumatoid arthritis and its effects on incidence and arthritis index were studied. The results were as folllows; It was exhibited that medicating corilagin inhibited the infiltration of activated T lymphocytes into an inflammatory joint. The production of IgG and IgM that were RF (rheumatoid factor) and inflammatory cytokine, IL-6 and $TNF-{\alpha}$were reduced. After measuring $IFN-{\gamma}$and IL-4, it was found that it was shifted into Th2 immune response as increasing in IL-4. After liver function test, studies on liver poisoning of AST/ALT should be continued.

Anti-oxidative and immune-regulative Effects of Electro-acupuncture at SP6 in Aged Rats (삼음교(三陰交) 전침이 노화과정 흰쥐의 항산화능 및 면역능에 미치는 영향)

  • Song, Jong-Keun;Lee, Byung-Ryul;Yang, Gi-Young;Jeon, Ju-Hyun;Yim, Yun-Kyoung
    • Korean Journal of Acupuncture
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    • v.27 no.1
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    • pp.87-106
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    • 2010
  • Objective & Methods: The purpose of this study is to investigate the anti-oxidative and immuneregulative effects of electro-acupouncture(EA) at SP6(Sameumgyo) in aged rats. The author performed several experimental items including blood cell counts, blood chemistry, measurement of various oxidants and antioxidants in liver and spleen, analysis of various cytokines in spleen. The results are as follows. Results: 1. EA at SP6 significantly reduced the number of platelets in blood. 2. EA at SP6 significantly reduced NO concentration and significantly increased catalase activity in liver. 3. EA at SP6 significantly reduced NO concentration and significantly increased SOD activity, catalase activity and glutathione concentration in spleen. 4. EA at SP6 restored the increase of IL-4, IL-6 and the decrease of IFN-$\gamma$ in aged rat spleen. Conclusion: According to these results, it is postulated that EA at SP6 has an antioxidative effect through increasing the activities of antioxidative enzymes and inhibiting production of oxidized substances, as well as an immune regulative effect in aging process. In consequence, it is presumed that EA at SP6 may have an anti-aging effect.

The Experimental Study on Anti-thrombotic and Anti-inflammatory Effect of NeungaSoJeokTang(NSJT) (능아소적탕(稜莪消積湯)의 항혈전(抗血栓) 및 항염작용(抗炎作用)에 대한 실험적(實驗的) 연구(硏究))

  • Je, Jong-Min;Yoo, Dong-Youl
    • The Journal of Korean Obstetrics and Gynecology
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    • v.20 no.3
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    • pp.45-64
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    • 2007
  • Purpose: This study was performed to evaluate anti-thrombotic and anti-inflammatory effects of NeungaSoJeokTang water extract (NSJT). Methods: In the study of anti-inflammatory effects, NSJT was investigated using cultured cells and murine models. As for the parameters of inflammation, levels of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were determined in mouse lung fibroblast cells(mLFC) and RAW 264.7 cells. Results: Prior to the experiment, we evaluated sGOT, sGPT, BUN and creatine after the treatment. As a result, NSJT was innoxious on liver and kidney. In experiment of anti-thrombotic effect, NSJT inhibited the platelet aggregation induced by ADP and epinephrine, and inhibited pulmonary embolism induced by collagen and epinephrine. NSJT did not affect significantly the blood flow rate both in vitro and in vivo. NSJT increased platelet number and fibrinogen amount, and NSJT shortened PT and APTT in thrombus model induced by dextran. In experiment of anti-inflammatory effect, NSJT inhibited $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, COX-2 and NOS-II mRNA expression in a concentration-dependent manner in RAW 264.7 cell line, and inhibited significantly NO production at 50, 100 ${\mu}g/ml$, and also inhibited ROS production in a concentration-dependent manner. NSJT inhibited $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production significantly in serum of acute inflammation-induced Balb/c mice, and decreased $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production in spleen tissue, but increased $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production in liver tissue. NSJT increased survival rate at the 3th day in ICR mice with lethal endotoxemia induced by LPS. Conclusion: These results suggest that NSJT can be used for treating diverse female diseases caused by thrombosis and inflammation such as pelvic pain, pelvic inflammatory disease as well as vulvar pain due to vulvitis, vulvar vestibulitis and so on.

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The Experimental Study on Anti-inflammatory Effect of Cheongyeoljohyeoltangkamibang(CYJHT) (청열조혈탕가미방(淸熱調血湯加味方)의 항염작용(抗炎作用)에 대한 실험적(實驗的) 연구(硏究))

  • Lee, Jung-Hwa;Yoo, Dong-Youl
    • The Journal of Korean Obstetrics and Gynecology
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    • v.21 no.4
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    • pp.49-68
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    • 2008
  • Purpose: This study was performed to evaluate anti-inflammatory effects of Cheongyeoljohyeoltangkamibang water extract (CYJHT). Methods: In the study of anti-inflammatory effects. CYJHT was investigated using cultured cells and murine models. As for the parameters of inflammation. levels of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were determined in mouse lung fibroblast cells(mLFCs). RAW 264.7 cells and acute inflammation-induced mice. Results: 1. CYJHT showed a safety in cytotoxicity and toxicity of liver. 2. CYJHT effected scavenging activity on 2.2-diphenyl-1-picrylhydrazyl(DPPH) free radical, superoxide dismutase(SOD) and superoxide anion radical(SAR). 3. CYJHT in RAW 264.7 cell decreased IL-l$\beta$ mRNA expression at 100, 50 ${\mu}g$/ml and also decreased TNF-$\alpha$ mRNA expression at 100 ${\mu}g/ml$ and decreased COX-2. NOS-II mRNA expression and decreased IL-6 mRNA expression in a concentration-dependent manner. 4. CYJHT in RAW 264.7 cell decreased IL-l$\beta$ significantly at 100, 50 ${\mu}g$/ml and decreased IL-6. TNF-$\alpha$ significantly at 100 ${\mu}g$/ml. 5. CYJHT inhibited IL-l1$\beta$, IL-6 and TNF-$\alpha$ production significantly in serum of acute inflammation-induced mice. 6. CYJHT decreased IL-1$\beta$, IL-6 and TNF-$\alpha$ mRNA production significantly in spleen tissue. and also decreased IL-l$\beta$. TNF-$\alpha$ mRNA production significantly in liver tissue of acute inflammation-induced mice. Conclusion: These results suggest that CYJHT can be useful in treating diverse female diseases caused by inflammation such as menstrual pain. menstrual disorder. leukorrhea. pelvic inflammatory disease and so on.

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The Experimental Study on Anti-inflammatory Effect of Manbunbang (만분방(慢盆方)이 염증 관련 cytokines의 유전자 발현과 생성량에 미치는 영향)

  • Kwak, Sang-Ho;Yoo, Dong-Youl
    • The Journal of Korean Obstetrics and Gynecology
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    • v.22 no.2
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    • pp.26-42
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    • 2009
  • Purpose: This study was performed to evaluate the anti-inflammatory effect of Manbunbang extract (MBB). Methods: In order to understand the mechanism of anti-inflammatory effect of MBB, expression of cytokines and its levels in RAW 264.7 cell lines, as well as changes of cytokine gene expressions in serum, spleen, and liver tissues in acute inflammation induced mouse model were investigated. Results: 1. MBB significantly suppressed the expression levels of IL-1${\beta}$, TNF-${\alpha}$ and COX-2 mRNAs at 100 and 50 ${\mu}$g/m${\ell}$ concentrations, and IL-6 and NOS-II genes at 100, 50 and 10 ${\mu}$g/m${\ell}$ concentrations in RAW 264.7 cell lines, compared to those of the control. 2. MBB significantly reduced the production level of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ at 100 and 50 ${\mu}$g/m${\ell}$ concentrations in RAW 264.7 cell lines compared the those of the control. 3. MBB significantly reduced the production of IL-1${\beta}$, IL-6 and TNF-${\alpha}$ levels in sera of acute inflammation induced mice. 4. MBB significanlty suppressed the expression level of IL-1${\beta}$, TNF-${\alpha}$ mRNA in spleen tissues as well as IL-6 mRNA in liver tissues in acute inflammation induced mice. Conclusion: From the results above, anti-inflammatory effect of MBB through its immune regulation could be experimentally explained. Wide treatment of inflammatory diseases such as pelvic inflammation using MBB are recommended.

Loss of hepatic Sirt7 accelerates diethylnitrosamine (DEN)-induced formation of hepatocellular carcinoma by impairing DNA damage repair

  • Yuna Kim;Baeki E. Kang;Karim Gariani;Joanna Gariani;Junguee Lee;Hyun-Jin Kim;Chang-Woo Lee;Kristina Schoonjans;Johan Auwerx;Dongryeol Ryu
    • BMB Reports
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    • v.57 no.2
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    • pp.98-103
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    • 2024
  • The mammalian sirtuin family (SIRT1-SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor.

Effect of Supplementation of Acanthopanax senticosus on Growth Performance, Blood Biochemical Profiles and Expression of Pro-Inflammatory Cytokines in Broiler Chicks (육계에서 가시오갈피 급여에 따른 생산성, 혈액 생화학적 성상 및 면역 사이토카인 발현에 미치는 영향)

  • Jang, In-Surk;Moon, Yang Soo;Sohn, Sea Hwan
    • Korean Journal of Poultry Science
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    • v.42 no.3
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    • pp.197-204
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    • 2015
  • This study was performed to examine the effects of dietary Acanthopanax senticosus (AS) on growth performance, immune organ weights, blood biochemical parameters and the expression of pro-inflammatory cytokines in broiler chicks. A total of 120 4-day-old birds were given a basal diet (CON) or a basal diet supplemented with 0.5% (AS1) or 1.0% (AS2) AS powder until the birds were 35 days of age. There was no difference in body weight, total gain, feed intake or immune organ weights among the treatment groups. However, the feed conversion ratio in the AS2 group was lower (p<0.05) than that in the CON group. Serum biochemical components, including AST (aspartate aminotransferase), ALT (alanine aminotransferase), albumin and total protein, were not affected by the dietary treatments, whereas glucose and triglyceride levels increased (p<0.05) in the AS2 group compared with the CON group. The AS1 group exhibited decreased mRNA expression (p<0.05) of IFN-${\gamma}$ in white blood cells and iNOS in the liver compared with the CON group. The other pro-inflammatory cytokines were unaffected by dietary AS supplementation, although there was a trend towards decreased expression of these genes, including those encoding Il-$1{\beta}$, IL-6 and TNF-${\alpha}$. In conclusion, dietary supplementation with 0.5% AS decreased the expression of several pro-inflammatory cytokines without affecting growth performance, suggesting that this supplement might be applicable as an immunoregulatory feed additive in broiler chicks.

Immunomodulatory effects of fermented Platycodon grandiflorum extract through NF-κB signaling in RAW 264.7 cells

  • Park, Eun-Jung;Lee, Hae-Jeung
    • Nutrition Research and Practice
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    • v.14 no.5
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    • pp.453-462
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    • 2020
  • BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG), an oriental herbal medicine, has been known to improve liver function, and has both anti-inflammatory and antimicrobial properties. However, little is known about the immune-enhancing effects of PG and its mechanism. In this study, we aimed to investigate whether fermented PG extract (FPGE), which has increased platycodin D content, activates the immune response in a murine macrophage cell line, RAW 264.7. MATERIALS/METHODS: Cell viability was determined by Cell Counting Kit-8 assay and the nitric oxide (NO) levels were measured using Griess reagent. Cytokine messenger RNA levels of were monitored by quantitative reverse transcription polymerase chain reaction. To investigate the molecular mechanisms underlying immunomodulatory actions of FPGE in RAW 264.7 cells, we have conducted luciferase reporter gene assay and western blotting. RESULTS: We found that FPGE treatment induced macrophage cell proliferation in a dose-dependent manner. FPGE also modulated the expression of NO and pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The activation and phosphorylation levels of nuclear factor kappa B (NF-κB) were increased by FPGE treatment. Moreover, 5-aminoimidazole-4-carboxamide ribonucleotide, an activator of AMP-activated kinase (AMPK), significantly reduced both lipopolysaccharides- and FPGE-induced NF-κB reporter gene activity. CONCLUSIONS: Taken together, our findings suggest that FPGE may be a novel immune-enhancing agent acting via AMPK-NF-κB signaling pathway.