• Title/Summary/Keyword: cytokines production

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Detection of TNF-alpha in Serum as the Effect of Corticosteroid to the Myocardial Protection in Cardiopulmonary Bypass (체외순환시 스테로이드의 심근보호효과에 관한 혈청내 TNF-alpha 측정의 의의)

  • 최영호;김욱진;김태식;조원민;김학제
    • Journal of Chest Surgery
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    • v.31 no.5
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    • pp.502-508
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    • 1998
  • Proinflammatory cytokines such as tumor necrosis factor-$\alpha$(TNF-$\alpha$) have been implicated in myocardial and organ dysfunction associated with postperfusion syndrome. We tested the hypothesis that cytokine productions are depressed by preoperative cortiosteroid injection for cardiopulmonary bypass(CPB) and the postoperative courses will be better than without steriod pretreated cases. Cardiac surgery was performed in randomized blind fashion for 20 patients from June 1996 to September 1996. In the steroid group(n=10), corticosteroid(dexamethasone 1 mg/kg) was injected 1 hour before anesthetic induction, but in the control group(n=10), nothing was injected. Each of groups were sampled 11 times as scheduled for TNF-$\alpha$ bioassays. We have checked EKG, cardiac enzymes(CPK, LDH with isoenzyme), WBC count preoperative day, one day and three days after operation. Viatal signs were continuously monitored for three postoperaive days. In the postoperative period three patients in the control group had elevated body temperature and four patients had hypotension that required considerable intravenous fluid administration. But steroid injected patients showed normal body temperture and acceptable blood pressures without supportive treatment. CPK enzymes rose in control group higher than steroid group at postoperative 1st and 3rd day(CPK; 1122$\pm$465 vs 567$\pm$271, 864$\pm$42 vs 325$\pm$87), and CPK-MB enzymes rose in control group higher than steroid group at postoperative 1st day(106.4$\pm$115.1 vs 29.5$\pm$22.4)(P=0.02). Arterial tumor necrosis factor-$\alpha$ rose during cardiopulmonary bypass, peaking at 5 minutes before the end of aortic cross clamping(ACC-5min) in steroid group(11.9$\pm$4.7 pg/ml), and 5 minutes before the end of cardiopulmonary bypass(CPB-5min) in control group(22.3$\pm$6.8 pg/ml). The steroid pretreated patients had a shorter period of time in respirator suport time, ICU stay day, hospital admission day. We conclude that corticosteroid suppress cytokine production during and after cardiopulmonary bypass, and may improve the postoperative course through inhibition of reperfusion injury such as myocardial stunning and hemodynamic instability.

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Anti-inflammatory Activity of Antimicrobial Peptide Protaetiamycine 2 Derived from the Protaetia brevitarsis seulensis (흰점박이꽃무지 유래 항균 펩타이드 프로테티아마이신 2의 항염증활성)

  • Lee, Joon Ha;Baek, Minhee;Lee, Hwa Jeong;Kim, In-Woo;Kim, Sun Young;Seo, Minchul;Kim, Mi-Ae;Kim, Seong Hyun;Hwang, Jae Sam
    • Journal of Life Science
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    • v.29 no.11
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    • pp.1218-1226
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    • 2019
  • The white-spotted flower chafer Protaetia brevitarsis seulensis is a medicinally beneficial and important edible insect species. We previously performed an in silico analysis of the Protaetia brevitarsis seulensis transcriptome to identify putative antimicrobial peptides and then tested their antimicrobial and hemolytic activities. These peptides had potent antimicrobial activities against bacteria and yeast without inducing hemolysis. In the present study, the cationic antimicrobial peptide, protaetiamycine 2, was selected for further assessment of its anti-inflammatory properties in mouse macrophage Raw264.7 cells. Protaetiamycine 2 treatment of Raw264.7 cells suppressed LPS-induced nitric oxide production and reduced the expression of inducible nitric oxide synthase and cyclooxygenase-2, as determined by real-time PCR and western blotting. The expression of proinflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) was also attenuated through the MAPKs and $NF-{\kappa}B$ signaling. We also confirmed that protaetiamycine 2 bound to bacterial cell membranes by a specific interaction with LPS. Collectively, these data obtained from LPS-induced Raw264.7 cells indicated that protaetiamycine 2 could have both antimicrobial and anti-inflammatory properties.

Inhibiting Effecposets of Gungguijohyeoleum on the Development of Experimentally-induced Endometriosis in the Rats (궁귀조혈음(芎歸調血飮)이 흰쥐의 자궁내막증 형성 억제에 미치는 영향)

  • Choi, Byun-Tak;Seo, Il-Bock;Lee, Dong-Nyung;Kim, Hyung-Jun
    • The Journal of Korean Obstetrics and Gynecology
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    • v.21 no.3
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    • pp.34-59
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    • 2008
  • Purpose: This study was performed to investigate the inhibiting effects of Gungguijohyeoleum on the development of experimentally-induced endometriosis in rats. Methods: Endometriosis was induced in rats by autotransplanting uterine tissue to the peritoneum and we divided them into three groups: (1) sham-operated group(n=8), (2) surgically induced endometriosis and untreated control group(n=8), (3) surgically induced endometriosis and Gungguijohyeoleum treated group(n=8), Gungguijohyeoleum was orally administrated for 15 days after operation. Then we measured the body weight, the volumes of endometriotic implants, the weight of uterus and ovary, and investigated the concentrations of cytokines(MCP-1, $TNF-{\alpha}$, $IL-1{\beta}$, IL-6) in peritoneal fluids. Histopathology, immunohistochemistry for COX-2 and VEGF, and histochemistry for mast cell in transplanted uterine tissue were performed. Results: - The volume ($mm^3$) of endometriotic implants in Gungguijohyeoleum treated group ($76.4{\pm}24.5$) was significantly decreased(p<0.05) compared with control group($222.1{\pm}109.1$). - The concentration (pg/ml) of MCP-1 in peritoneal fluids in Gungguijohyeoleum treated group ($1060.8{\pm}280.8$) was significantly decreased(p<0.05) compared with control group($1412.5{\pm}345.7$). - The concentration (pg/ml) of $TNF-{\alpha}$ in peritoneal fluids in Gungguijohyeoleum treated group ($827.5{\pm}219.9$) was significantly decreased(p<0.01) compared with control group($1126.2{\pm}139.9$). - The concentration (pg/ml) of $IL-1{\beta}$ in peritoneal fluids in Gungguijohyeoleum treated group($83.4{\pm}9.0$) was significantly decreased(p<0.01) compared with control group($105.3{\pm}17.6$). - The concentration (pg/ml) of IL-6 in peritoneal fluids in Gungguijohyeoleum treated group($108.9{\pm}15.7$) was decreased compared with control group($122.8{\pm}19.3$). - Histopathologically, proliferation of endometriotic epithelia, infiltration of inflammatory cells and angiogenesis in transplanted uterine tissue of Gungguijohyeoleum treated group were weakly observed than those of control group. - The percentage(%) of positive epithelial layers for COX-2 in Gungguijohyeoleum treated group($56.8{\pm}12.8$) was significantly decreased(p<0.01) compared with control group($75.1{\pm}16.3$). -The VEGF expression of endometriotic epithelia, neovascular endothelia and stromal cells in transplanted uterine tissue of Gungguijohyeoleum treated group was weakly observed than that of control group. - The numbers of mast cells in transplanted uterine tissue in Gungguijohyeoleum treated group($35.4{\pm}18.4$) were significantly decreased(p<0.01) compared with control group ($91.0{\pm}28.3$). Conclusion: On the basis of these results, we concluded that Gungguijohyeoleum has inhibiting effects on the development of transplanted uterine tissue. And these effects may be related with decreased production of MCP-1, $TNF-{\alpha}$, $IL-1{\beta}$, COX-2, VEGF and mast cells by administration of Gungguijohyeoleum.

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Comparative Study of Litsea japonica Leaf and Fruit Extract on the Anti-inflammatory Effects (까마귀쪽나무 열매와 잎의 항염증 효과 비교 연구)

  • Namkoong, Seung;Jang, Seon-A;Sohn, Eun-Hwa;Bak, Jong Phil;Sohn, Eunsoo;Koo, Hyun Jung;Yoon, Weon-Jong;Kwon, Jung-Eun;Jeong, Yong Joon;Meng, Xue;Han, Hyo-Sang;Kang, Se Chan
    • Korean Journal of Plant Resources
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    • v.28 no.2
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    • pp.145-152
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    • 2015
  • The present study aimed to investigate comparative anti-inflammatory effects of Litsea japonica fruit and leaf extract considering the balance of safety and efficacy. Dose response studies were performed to determine the inhibitory effects of 70% EtOH extract of leaf (L70%) on the pro-inflammatory enzymes expression, COX-2/PGE2 and NO/iNOS, and pro-inflammatory cytokines production, IL-$1{\beta}$, IL-6, and TNF-$\alpha$ in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. We also examined comparative effects of 30 and 70% EtOH extract of fruits (F30% and F70%) at low concentration ($10{\mu}g/ml$ ) in the same conditions. L70% at 50 and $100{\mu}g/ml$ showed inhibitory effects on almost all the inflammatory mediators we examined except for COX-2 regulation, but there were no effects at $10{\mu}g/ml$. Since $100{\mu}g/ml$ of L70% have 18.2% cytotoxicity, we compared the effects of fruit extract, F30% and F70% at $10{\mu}g/ml$ on the regulation of NO/iNOS, PGE2, IL-$1{\beta}$, IL-6, and TNF-$\alpha$ and obtained that fruit extacts are more efficacious and safe than leaf. This study suggests that the 30% EtOH fraction of L. japonica fruit could be a good candidate for development as a functional food supplement in the prevention of inflammatory disorders.

Proanthocyanidins Suppresses Lipopolysaccharide-stimulated Inflammatory Responses via Heme Oxygenase-1 Induction in RAW264.7 Macrophages (프로안토시아니딘의 항염증효과)

  • Cheon, Hye-Jin;Park, Sun Young;Jang, Hee-Ji;Cho, Da-Young;Jung, Jiwon;Park, Gimin;Jeong, Kyeong Mi;Kim, Jin-Kyung
    • Journal of Life Science
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    • v.29 no.4
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    • pp.484-491
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    • 2019
  • Proanthocyanidins are naturally occurring polyphenolic compounds abundant in many vegetables, plant skins (rind/bark), seeds, flowers, fruits, and nuts. Numerous in vitro and in vivo studies have demonstrated myriad effects potentially beneficial to human health, such as antioxidation, immunomodulation, DNA repair, and antitumor activity. Among immune cells, macrophages are crucial players in a variety of inflammatory responses to environmental conditions. However, it has been widely reported that macrophages cause chronic inflammation and are involved in a variety of diseases, such as obesity, diabetes, metabolic syndrome, and cancer. In this study, we report the suppressive effect of proanthocyanidins via the heme oxygenase-1 (HO-1)-related system, on the immune response of the LPS-stimulated mouse macrophage cell line RAW264.7. Increased HO-1 expression at mRNA and protein levels were found in proanthocyanidins-treated RAW264.7 cells. Further, proanthocyanidins enhanced nuclear factor-erythroid 2-related factor 2 translocation into the nucleus. RAW264.7 cells were treated with lipopolysaccharide (LPS) with or without proanthocyanidins, and inflammatory mediator expression levels were assessed. Proanthocyanidins treatment resulted in the attenuation of nitric oxide production and inducible nitric oxide synthase expression in LPS-stimulated RAW264.7 cells. In addition, mRNA and protein expression of proinflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin-6, was inhibited by proanthocyanidins treatment in LPS-stimulated RAW264.7 cells. These findings support proanthocyanidins as a promising anti-inflammatory agent.

Two new triterpenoid saponins derived from the leaves of Panax ginseng and their antiinflammatory activity

  • Li, Fu;Cao, Yufeng;Luo, Yanyan;Liu, Tingwu;Yan, Guilong;Chen, Liang;Ji, Lilian;Wang, Lun;Chen, Bin;Yaseen, Aftab;Khan, Ashfaq A.;Zhang, Guolin;Jiang, Yunyao;Liu, Jianxun;Wang, Gongcheng;Wang, Ming-Kui;Hu, Weicheng
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.600-605
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    • 2019
  • Background: The leaves and roots of Panax ginseng are rich in ginsenosides. However, the chemical compositions of the leaves and roots of P. ginseng differ, resulting in different medicinal functions. In recent years, the aerial parts of members of the Panax genus have received great attention from natural product chemists as producers of bioactive ginsenosides. The aim of this study was the isolation and structural elucidation of novel, minor ginsenosides in the leaves of P. ginseng and evaluation of their antiinflammatory activity in vitro. Methods: Various chromatographic techniques were applied to obtain pure individual compounds, and their structures were determined by nuclear magnetic resonance and high-resolution mass spectrometry, as well as chemical methods. The antiinflammatory effect of the new compounds was evaluated on lipopolysaccharide-stimulated RAW 264.7 cells. Results and conclusions: Two novel, minor triterpenoid saponins, ginsenoside $LS_1$ (1) and 5,6-didehydroginsenoside $Rg_3$ (2), were isolated from the leaves of P. ginseng. The isolated compounds 1 and 2 were assayed for their inhibitory effect on nitric oxide production in LPS-stimulated RAW 264.7 cells, and Compound 2 showed a significant inhibitory effect with $IC_{50}$ of $37.38{\mu}M$ compared with that of NG-monomethyl-L-arginine ($IC_{50}=90.76{\mu}M$). Moreover, Compound 2 significantly decreased secretion of cytokines such as prostaglandin $E_2$ and tumor necrosis factor-${\alpha}$. In addition, Compound 2 significantly suppressed protein expression of inducible nitric oxide synthase and cyclooxygenase-2. These results suggested that Compound 2 could be used as a valuable candidate for medicinal use or functional food, and the mechanism is warranted for further exploration.

Studies on Antioxidant, Anti-inflammatory and Whitening Effects of Oriental Herbal Extracts (Mix) including Eucommiae cortex (두충을 포함하는 한방추출물(Mix)의 항노화, 항염, 미백 효능 활성에 관한 연구)

  • Choi, Da Hee;Kim, Mi Ran;Kim, Min Young;Kim, Ho Hyun;Park, Sun-Young;Hwang, Hyung Seo
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.45 no.1
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    • pp.37-47
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    • 2019
  • Recently, due to the increase in skin diseases caused by particulate matter, endocrine disruptor and environmental changes, the trend of development of cosmetic materials has been shifting to the more safe and effective ingredients based on natural materials rather than existing synthetic compounds like steroids and antihistamines. This study aimed to develop a new natural cosmetic materials using oriental herbs such as Eucommiae cortex, Alpinia oxyphylla Miquel and Bombyx batryticatus. First, DPPH assay was performed to examine the antioxidative activity of the herbal extract (Mix) and 98.8% DPPH radical scavenging activity was confirmed at $400{\mu}g/mL$ concentration of it. In order to confirm the whitening efficacy of oriental herbal extracts(mix), the amount of melanin synthesized after stimulation of ${\alpha}-MSH$ with B16F10 cells was measured. Results showed that it was decreased to 27.1% comparing with the only ${\alpha}-MSH$ treated group, which confirmed the whitening efficacy. Also, both nitric oxide(NO) production and iNOS and COX-2 expression were significantly reduced in RAW264.7 macrophages activated by LPS in the presence of the extracts(Mix). The mRNA expression of the inflammatory cytokines such as $IL-1{\alpha}$, $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ was also analyzed to confirm the inhibition effect of the extracts on inflammation. Finally, to confirm the enhancement of skin barrier function, the expression of claudin 1 gene, a tight junction protein, was observed using human keratinocyte HaCaT cells and increased as concentration dependent manner. From these results, it is concluded that the oriental herbal extracts(Mix) containing Eucommiae cortex, Alpinia oxyphylla Miquel and Bombyx batryticatus is effective for antioxidant, anti-inflammation, skin whitening, and skin barrier and thus could be applied as a new natural cosmetic material.

Anti-inflammatory Effects of Hemistepta lyrata Bunge in LPS-stimulated RAW 264.7 Cells through Regulation of MAPK Signaling Pathway (LPS로 유도된 RAW 264.7 대식세포의 염증반응에서 MAPK 신호경로 조절을 통한 지칭개 에탄올 추출물의 항염증 효과)

  • Kim, Chul Hwan;Lee, Young-Kyung;Jeong, Jin-Woo;Hwang, Buyng Su;Jeong, Yong Tae;Oh, Yong Taek;Cho, Pyo Yun;Kang, Chang-Hee
    • Korean Journal of Plant Resources
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    • v.34 no.1
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    • pp.23-30
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    • 2021
  • Hemistepta lyrata Bunge (HL) has been used as a folk remedy to treat cancer, inflammation, bleeding, hemorrhoids and fever, and leaves and young shoots have been used as famine food. Nevertheless, the biological activities and underlying mechanisms of the anti-inflammatory effects remain unclear. In this study, it was undertaken to explore the functions of the aerial part of HL as a suppressor of inflammation by using RAW 264.7 cells. As immune response parameters, the productions of as nitric oxide (NO) and prostaglandin E2 (PGE2), cytokines such tumor necrotic factor (TNF)-α and interleukin (IL)-6 were evaluated. Although the release of TNF-α remained unchanged in HL-treated RAW 264.7 cells, the productions of NO, PGE2 and IL-6 were significantly increased at concentrations with no cytotoxicity. Furthermore, HL significantly attenuated the mitogen-activated protein kinases (MAPK) pathway including decreasing the phosphorylation of the extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein kinases. Collectively, this study provides evidence that HL inhibits the production of major pro-inflammatory molecules in LPS-stimulated RAW 264.7 cells via suppression of ERK and P38 MAPK signaling pathways. These findings suggest that the beneficial therapeutic effects of HL may be attributed partly to its ability to modulate immune functions in macrophages.

Study on skin anti-inflammatory activity of fig (Ficus carica L.) fruit extract fractions (무화과(Ficus carica L.) 열매 추출 분획의 피부 항염증 활성 연구)

  • Hee Joon Kwon;Geun soo Lee;Jin Hwa Kim;Soon Woo Kwon;Hyung seo Hwang
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.416-423
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    • 2023
  • Figs has known to have antioxidant, whitening, anti-inflammatory, and antibacterial effects in their leaves, roots, stems, latex, and fruits. In order to develop cosmetic materials based on natural products, we have studied on the skin activity of the ficin in latex as well as the whitening function of the fruit extract with 70% ethanol, and used it as a raw material for released cosmetic product. However, there is little research on the demand for the development of new eutectic solvent extraction methods and its ability to control skin inflammation and psoriasis regulation. Thus, in this study, we evaluated the effectiveness of fig fruit extracts and fractions using eutectic solvent extraction for skin inflammation control and psoriasis. First, fig fruits were extracted under optimal eutectic solvent conditions and fractionated with n-hexane, dichloromethane, ethyl acetate, and butanol. First, the antioxidant activity and inhibition of nitric oxide (NO) production were confirmed in mouse macrophage RAW264.7 cells. In addition, as a result of observing the mRNA expression through RT-PCR, pro-inflammatory cytokines such as TNF-α, IL1α, and IL-1β were suppressed significantly in the hexane, dichloromethane, and ethyl acetate fractions. In addition, it was confirmed in TNF-α stimulated HaCaT keratinocyte model. Finally, chemokine CC motif ligand 20 (CCL20), marker gene of human psoriasis skin disease, was significantly suppressed in the hexane, dichloromethane, and ethyl acetate fractions. These results suggested its anti-inflammatory and skin soothing effect and the possibility of development as an excellent skin soothing natural cosmetic material in the future through future clinical trials.