• Title/Summary/Keyword: Proinflammatory mediators

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Antioxidant and Inflammatory Mediators Regulation Effects of the Roots of Opuntia humifusa (천년초 뿌리의 항산화 및 염증 매게 물질 조절 효과)

  • Kim, Ye Jin;Park, Chan Ik;Kim, Soo Jin;Ahn, Eun Mi
    • Journal of Applied Biological Chemistry
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    • v.57 no.1
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    • pp.1-5
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    • 2014
  • The roots of Opuntia humifusa (OHR) were extracted with 80% aqueous MeOH and the concentrated extract was partitioned with EtOAc, n-butanol and $H_2O$, successively. The fractions were tested using DPPH and ABST radical scavenging method. The all fractions showed potent scavenging effects. The scavenging effect of the EtOAc fraction was higher than the other fractions, with $IC_{50}$ values as DPPH; $77.0{\pm}1.38{\mu}g/mL$, ABTS: $26.3{\pm}2.02{\mu}g/mL$. And, we investigated anti-inflammatory activities by examining the effects of the OHR fractions on pro-inflammatory cytokine release in the human mast cells (HMC-1). Treatment with OHR fractions clearly reduced the release of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, interleukin (IL)-6 and interleukin (IL)-8) in PMACI-stimulated HMC-1 cells. The results showed the potential of OHR as an excellent antioxidant substance and inhibiting inflammatory mediators. Therefore, OHR may be used as a therapeutic approach to various inflammatory diseases.

Efficacies of the Modified Ultrafiltration and Peritoneal Dialysis in Removing Inflammatory Mediators After Pediatric Cardiac Surgery (소아 개심술 후 변형 초여과법과 복막투석의 염증 매개체 (inflammatory mediator)의 감소에 대한 효과)

  • 성시찬;정민호
    • Journal of Chest Surgery
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    • v.34 no.10
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    • pp.745-753
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    • 2001
  • capillary leak syndrome and organ dysfunction in infants. Removing harmful cytokines and complement anaphylatoxins after cardiopulmonary bypass may attenuate this response. This study was conducted to see if the modified ultrafiltration and postoperative peritoneal dialysis can reduce plasma inflammatory mediators in pediatric cardiac surgery. Material and Method: 30 infants (age 1.1 to 12.6 months) who underwent closures of ventricular septal defect using cardiopulmonary bypass (CPB) were enrolled in this study. These patients were divided into three groups; 10 patients selected randomly underwent modified ultrafiltration (Group U), 10 with small body weights ($\leq$5 kg) received postoperative peritoneal dialysis (Group P), and 10 patients did not undergo modified ultrafiltration nor receivcd peritoneal dialysis (Group C). Serum samples were obtained before and after CPB, and after peritoneal dialysis. Effluents sample were also obtained after modified ultrafiltration or peritoneal dialysis. C3a and interleukin-6 (IL-6) were measured by radioimmunoassay and enzyme-linked immunosorbent assay respectively. Result: There was no differences in CPB time, aortic cross-clamping title, and lowest temperature during CPB. The effluents of peritoneal dialysis contained significant amount of C3a and IL-6, but there was no definitive decrease of serum concentration of C3a and IL-6. The effluents of modified ultrafiltration had some amount of C3a and negligible IL-6, and there was no decrease of serum concentration of these (actors. Conclusion: The effluents of peritoneal dialysis contained significant amount of proinflammatory cytokine, IL-6 and complement, C3a. However this study failed to elucidate the decrease in serum levels of these factors. The modified ultrafiltration also was not able to reduce the serum levels of C3a or IL-6 in our study as well.

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Effect of Scutellariae Radix Extract on the Proinflammatory Mediators in Raw 264.7 Cells Induced by LPS (황금(黃芩)이 LPS로 유발된 Raw 264.7 Cells의 염증인자에 미치는 영향)

  • Yoon, Seok-Bin;Han, Hyo-Sang;Lee, Young-Jong
    • The Korea Journal of Herbology
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    • v.26 no.2
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    • pp.75-81
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    • 2011
  • Objectives : This study aims at examining the anti-inflammatory effects of Scutellariae Radix extract. Methods : Scutellariae Radix was hot water extracted to make the samples(SR) for the experiment. Their effects were examined on the increase of cell viability in mouse macrophage Raw 264.7 cells, the creation of nitric oxide(NO) in lipopolysaccharide(LPS)-induced Raw 264.7 cells, and the creation of cytokines of interleukin(IL)-$1{\beta}$ and others. Results : The results of the experiment are as follows. 1. The MTT assay was carried out to check the cellular toxicity of the water extract of Scutellariae Radix. The results were found no significant toxicity caused to macrophages by the water extract of Scutellariae Radix. 2. The water extract of Scutellariae Radix significantly restricted the increase of NO in the LPS-induced macrophages after 24-hour culture. 3. The water extract of Scutellariae Radix significantly restricted the creation of IL-6, IL-10, IL-12p40, IL-17, interferon-inducible protein(IP)-10, keratinocyte-derived chemokine(KC), and vascular endothelial growth factor(VEGF) in the LPS-induced macrophages at the concentration of $25{\mu}g/mL$ or higher. Conclusion : The samples(SR) of hot water extract of Scutellariae Radix caused no significant cellular toxicity to macrophages and significantly restricted the creation of NO, IL-6, IL-10, IL-12p40, IL-17, IP-10, KC, and VEGF in the LPS-induced macrophages at $25{\mu}g/mL$ or higher, thus demonstrating significant anti-inflammatory effects.

Carpomitra costata Extract Alleviates Lipopolysaccharide-induced Neuroinflammatory Responses in BV2 Microglia through the Inactivation of NF-κB Associated with the Blockade of the TLR4 Pathway and ROS Generation

  • Park, Cheol;Cha, Hee-Jae;Hong, Su-Hyun;Kim, Suhkmann;Kim, Heui-Soo;Choi, Yung Hyun
    • Journal of Marine Bioscience and Biotechnology
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    • v.12 no.1
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    • pp.29-39
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    • 2020
  • In this study, we investigated the inhibitory potential of an ethanol extract of Carpomitra costata (EECC) (Stackhouse) Batters, a brown alga, against neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results showed that EECC significantly suppressed the LPS-induced secretion of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E2, with no significant cytotoxic effects. EECC also inhibited the LPS-induced expression of their regulatory enzymes, such as inducible NO synthase and cyclooxygenase-2. In addition, EECC downregulated the LPS-induced expression and production of the proinflammatory cytokines, tumor necrosis factor-α and interleukin-1β. In the mechanistic assessment of the antineuroinflammatory effects, EECC was found to inhibit the nuclear translocation and DNA binding of nuclear factor-kappa B (NF-κB) by disrupting the degradation of the κB-α inhibitor in the cytoplasm. Moreover, EECC effectively suppressed the enhanced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88, as well as the binding of LPS to TLR4 in LPS-treated BV2 cells. Furthermore, EECC markedly reduced the LPS-induced generation of reactive oxygen species (ROS), demonstrating a strong antioxidative effect. Collectively, these results suggest that EECC repressed LPS-mediated inflammatory action in the BV2 microglia through the inactivation of NF-κB signaling by antagonizing TLR4 and/or preventing ROS accumulation. While further studies are needed to fully understand the anti-inflammatory effects associated with the antioxidant activity of EECC, the current findings suggest that EECC has a potential advantage in inhibiting the onset and treatment of neuroinflammatory diseases.

Anti-inflammatory Effects of Fermented Houttuyniae Herba Water Extract on LPS-induced Mouse Macrophage (발효 어성초(魚腥草) 물추출물의 마우스 대식세포 항염활성 연구)

  • Lee, Ji-Young;Lee, Young-Jong;Park, Wan-Su
    • The Korea Journal of Herbology
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    • v.25 no.3
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    • pp.27-34
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    • 2010
  • Objectives : The purpose of this study is to investigate the effect of Fermented Houttuyniae Herba Water Extract (HL) on production of proinflammatory mediators in mouse macrophage RAW 264.7 cells. Methods : Cell viabilities were measured by MTT assay. Effect of HL on nitric oxide (NO) production from RAW 264.7 cells was accessed by Griess reagent assay. Effect of HL on productions of inflammatory cytokines such as interleukine (IL)-17, Interferon $\gamma$-inducible protein (IP)-10, Eotaxin, IL-5, Monocyte Chemotactic Protein-3 (MCP-3), and IL-13 in LPS-induced RAW 264.7 cells was accessed by a multiplex bead array assay based on xMAP technology. Results : The results of the experiment are as follows. 1. Incubation with HL for 24 hours showed significant increase in cell viability of RAW 264.7 mouse macrophages (P < 0.05). 2. HL showed to inhibit NO production from RAW 264.7 cells at the concentrations of 25 and 50 ug/mL significantly (P < 0.05). 3. HL inhibited significantly NO production in LPS-induced RAW 264.7 cells at the concentrations of 25, 50, 100 and 200 ug/mL (P < 0.05). 4. HL inhibited significantly IL-17, IP-10 and Eotaxin in LPS-induced RAW 264.7 cells at the concentrations of 25, 50, 100 and 200 ug/mL (P < 0.05). Conclusions : These results suggest that HL has anti-inflammatory moiety related with its inhibition of NO, IL-17, IP-10, and Eotaxin in macrophages.

Anti-oxidative and anti-inflammatory effect of Do-Ki-Tang methanol extract in mouse macrophage cells (마우스 대식세포에서 도기탕 (導氣湯) 메탄올 추출물의 항산화 및 항염증 효과)

  • Kim, Dong-Wan;Yun, Hyun-Jeong;Heo, Jun-Young;Kim, Tae-Hoon;Cho, Hyun-Jin;Park, Sun-Dong
    • The Korea Journal of Herbology
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    • v.25 no.4
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    • pp.103-112
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    • 2010
  • Objective : The aim of this study was to determine whether methanol extract of Do-Ki-Tang (DKT) inhibit free radical generation and production of nitrite an index of NO, $PGE_2$, iNOS, COX-2 and pro-inflammatory cytokines such as TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods : Cytotoxic activity of extract on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. The expression level of inflammatory response-related proteins was confirmed by western blot. The production of proinflammatory cytokines was measured by ELISA. Results : Our results indicated that DKT scavenged DPPH radical and nitric oxide in vitro. Moreover, DKT significantly inhibited the LPS-induced NO, $PGE_2$ production and iNOS, COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 formation in macrophages. Furthermore, DKT treatment also blocked LPS-induced intracellular ROS production and the activation of NF-${\kappa}B$ and MAPKs. Conclusion : Our data suggest that the anti-inflammatory effect of DKT is mediated through down-modulation of pro-inflammatory mediators and cytokines by blocking the signaling pathways of NF-${\kappa}B$ and MAPKs. These inhibitory effects by DKT represent a potential therapeutic approach to the treatment of inflammatory diseases.

Dimethyl Cardamonin Exhibits Anti-inflammatory Effects via Interfering with the PI3K-PDK1-PKCα Signaling Pathway

  • Yu, Wan-Guo;He, Hao;Yao, Jing-Yun;Zhu, Yi-Xiang;Lu, Yan-Hua
    • Biomolecules & Therapeutics
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    • v.23 no.6
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    • pp.549-556
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    • 2015
  • Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key "late" proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKC${\alpha}$). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKC${\alpha}$ signaling pathway.

The Aqueous Extract of Radio-Resistant Deinococcus actinosclerus BM2T Suppresses Lipopolysaccharide-Mediated Inflammation in RAW264.7 Cells

  • Kim, Myung Kyum;Jang, Seon-A;Namkoong, Seung;Lee, Jin Woo;Park, Yuna;Kim, Sung Hyeok;Lee, Sung Ryul;Sohn, Eun-Hwa
    • Journal of Microbiology and Biotechnology
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    • v.30 no.4
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    • pp.583-590
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    • 2020
  • Deinococcus actinosclerus BM2T (GenBank: KT448814) is a radio-resistant bacterium that is newly isolated from the soil of a rocky hillside in Seoul. As an extremophile, D. actinosclerus BM2T may possess anti-inflammatory properties that may be beneficial to human health. In this study, we evaluated the anti-inflammatory effects of BM2U, an aqueous extract of D. actinosclerus BM2T, on lipopolysaccharide (LPS)-mediated inflammatory responses in RAW264.7 macrophage cells. BM2U showed antioxidant capacity, as determined by the DPPH radical scavenging (IC50 = 349.3 ㎍/ml) and ORAC (IC50 = 50.24 ㎍/ml) assays. At 20 ㎍/ml, BM2U induced a significant increase in heme oxygenase-1 (HO-1) expression (p < 0.05). BM2U treatment (0.2-20 ㎍/ml) significantly suppressed LPS-induced increase in the mRNA expression of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 (p < 0.05). BM2U treatment also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which are involved in the production of inflammatory mediators. BM2U treatment also inhibited the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs): JNK, ERK, and p-38 (p < 0.05). Collectively, BM2U exhibited anti-inflammatory potential that can be exploited in attenuating inflammatory responses.

Antiallodynic Effect of Thalidomide and Morphine on Rat Spinal Nerve Ligation-induced Neuropathic Pain

  • Choi, Jeong-Il;Kim, Woong-Mo;Yoon, Myung-Ha;Lee, Hyung-Gon
    • The Korean Journal of Pain
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    • v.23 no.3
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    • pp.172-178
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    • 2010
  • Background: Tumor necrosis factor-alpha and other proinflammatory cytokines are becoming well recognized as key mediators in the pathogenesis of many types of neuropathic pain. Thalidomide has profound immunomodulatory actions in addition to their originally intended pharmacological actions. There has been debate on the analgesic efficacy of opioids in neuropathic pain. The aim of this study was to investigate the effect of thalidomide and morphine on a spinal nerve ligation model in rats. Methods: Male Sprague-Dawley rats weighing 100-120 g were used. Lumbar (L) 5 and 6 spinal nerve ligations were performed to induce neuropathic pain. For assessment of mechanical allodynia, mechanical stimulus using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of intraperitoneal thalidomide (6.25, 12.5, 25 and 50 mg/kg, respectively) and morphine (3 and 10 mg/kg, respectively) were examined on a withdrawal threshold evoked by spinal nerve ligation. Results: After L5 and 6 spinal nerve ligation, paw withdrawal thresholds on the ipsilateral side were significantly decreased compared with pre-operative baseline and with those in the sham-operated group. Intraperitoneal thalidomide and morphine significantly increased the paw withdrawal threshold compared to controls and produced dose-responsiveness. Conclusions: Systemic thalidomide and morphine have antiallodynic effect on neuropathic pain induced by spinal nerve ligation in rat. These results suggest that morphine and thalidomide may be alternative therapeutic approaches for neuropathic pain.

Ameliorative effects of atractylodin on intestinal inflammation and co-occurring dysmotility in both constipation and diarrhea prominent rats

  • Yu, Changchun;Xiong, Yongjian;Chen, Dapeng;Li, Yanli;Xu, Bin;Lin, Yuan;Tang, Zeyao;Jiang, Chunling;Wang, Li
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.1
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    • pp.1-9
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    • 2017
  • Intestinal disorders often co-occur with inflammation and dysmotility. However, drugs which simultaneously improve intestinal inflammation and co-occurring dysmotility are rarely reported. Atractylodin, a widely used herbal medicine, is used to treat digestive disorders. The present study was designed to characterize the effects of atractylodin on amelioration of both jejunal inflammation and the co-occurring dysmotility in both constipation-prominent (CP) and diarrhea-prominent (DP) rats. The results indicated that atractylodin reduced proinflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 in the plasma and inhibited the expression of inflammatory mediators iNOS and NF-kappa B in jejunal segments in both CP and DP rats. The results indicated that atractylodin exerted stimulatory effects and inhibitory effects on the contractility of jejunal segments isolated from CP and DP rats respectively, showing a contractile-state-dependent regulation. Atractylodin-induced contractile-state-dependent regulation was also observed by using rat jejunal segments in low and high contractile states respectively (5 pairs of low/high contractile states). Atractylodin up-regulated the decreased phosphorylation of 20 kDa myosin light chain, protein contents of myosin light chain kinase (MLCK), and MLCK mRNA expression in jejunal segments of CP rats and down-regulated those increased parameters in DP rats. Taken together, atractylodin alleviated rat jejunal inflammation and exerted contractile-state-dependent regulation on the contractility of jejunal segments isolated from CP and DP rats respectively, suggesting the potential clinical implication for ameliorating intestinal inflammation and co-occurring dysmotility.