• Title, Summary, Keyword: inflammatory mediators

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Anti-rheumatiod Arthritis Effects of I-Myo-San Water Extract (이묘산(二妙散)의 항(抗)류마티즘 효능(效能)에 대한 연구(硏究))

  • Lim, Chang-Kyung;Yun, Young-Gab
    • Herbal Formula Science
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    • v.17 no.1
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    • pp.99-111
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    • 2009
  • Rheumatoid arthritis is characterized by focal loss of cartilage due to an up-regulation of inflammatory pathways, which produce pro-inflammatory mediators, such as interleukin-1(IL-1), tumour necrosis factor alpha($TNF-\alpha$), prostaglantin, and nitric oxide(NO). We investigated the anti-arthritic effects of water extracts from Pellodendri cortex and Atractylodis rhizoma in vitro and in vivo. Each extract suppressed the production of inflammatory mediators(NO, $IL-1\beta$, $TNF-\alpha$, and prostaglandin $E_2$) and the expression of inducible NO synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated macrophages in a dose-dependent manner. These suppressive effects were synergistically increased by their combination. The same results were also observed in the rat osteoblast sarcoma cell line ROS17/2.8 stimulated with $IL-1\beta$, $IFN-\gamma,$ and $TNF-\alpha$. Moreover, the combination of these water extracts significantly suppressed collagen-induced mouse arthritis. These results suggest that the combination of water-extractable components of Pellodendri cortex and Atractylodis rhizoma may be useful for therapeutic drugs against rheumatoid arthritis, probably by suppressing the production of inflammatory mediators.

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Bacterial PAMPs and Allergens Trigger Increase in $[Ca^{2+}]_i$-induced Cytokine Expression in Human PDL Fibroblasts

  • Son, Ga-Yeon;Shin, Dong Min;Hong, Jeong Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.3
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    • pp.291-297
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    • 2015
  • An oral environment is constantly exposed to environmental factors and microorganisms. The periodontal ligament (PDL) fibroblasts within this environment are subject to bacterial infection and allergic reaction. However, how these condition affect PDL fibroblasts has yet to be elucidated. PDL fibroblasts were isolated from healthy donors. We examined using reverse transcription-polymerase chain reaction and measuring the intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$). This study investigated the receptors activated by exogenous bacterial pathogens (Lipopolysaccharide and peptidoglycan) and allergens (German cockroach extract and house dust mite) as well as these pathogenic mediators-induced effects on the intracellular $Ca^{2+}$ signaling in human PDL fibroblasts. Moreover, we evaluated the expression of pro-inflammatory cytokines (interleukin (IL)-$1{\beta}$, IL-6, and IL-8) and bone remodeling mediators (receptor activator of NF-${\kappa}B$ ligand and osteoprotegerin) and intracellular $Ca^{2+}$-involved effect. Bacterial pathogens and allergic mediators induced increased expression of pro-inflammatory cytokines, and these results are dependent on intracellular $Ca^{2+}$. However, bacterial pathogens and allergic mediators did not lead to increased expression of bone remodeling mediators, except lipopolysaccharide-induced effect on receptor activator of NF-${\kappa}B$ ligand expression. These experiments provide evidence that a pathogens and allergens-induced increase in $[Ca^{2+}]_i$ affects the inflammatory response in human PDL fibroblasts.

Synergic Effect of Quercetin and Astragalin from Mulberry Leaves on Ani-inflammation (상엽 유래 퀘세틴과 아스트라갈린의 항염증에 대한 상승효과)

  • Mok, Ji-Ye;Jeong, Seung-Il;Kim, Jang-Ho;Jang, Seon-Il
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.5
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    • pp.830-836
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    • 2011
  • The leaf of mulberry (Morus alba L) has long been used in Oriental medicine for the prevention or treatment of several diseases. However, little is known about the inhibitory effects of a single compound isolated from the mulberry leaves on inflammatory response. We are isolate a single compound of quercetin (3,3',4',5,7-pentahydroxyflavone) and astragalin (kaempferol-3-O-glucopyranoside) from the mulberry leaves, and then investigate the anti-inflammatory effects of quercetin, astragalin or quercetin plus astragalin in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. Each compound suppressed the production of inflammatory mediators (NO, $PGE_2$ and IL-6) in LPS-stimulated murine peritoneal macrophages in a dose-dependent manner. Especially, the cotreatment of quercetin (2.5 ${\mu}M$) and astragalin (2.5 ${\mu}M$) markedly suppressed the production and the expression of inflammatory mediators. These suppressive effects were synergistically increased by their combination. These results suggest that the combination of quercetin and astragalin from the mulberry leaves may be useful for therapeutic drugs against inflammatory immune diseases, probably by suppressing the production of inflammatory mediators.

Inhibitory Effects of Wisaengtang on Inflammatory Mediators in LPS-induced RAW264.7 Cells (위생탕(衛生湯)의 LPS로 유도된 RAW264.7 세포에서 염증매개체에 대한 억제효과)

  • Kim, Jung-Hee;Kim, Tae-Jun;Kim, Ee-Hwa;Kim, Yong-Min
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.32 no.3
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    • pp.48-57
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    • 2019
  • Objectives : This study examined the inhibitory effects of Wisaengtang(WST) on inflammatory mediators($NF-{\kappa}B$, COX-2, iNOS, IL-6) in cellular inflammatory responses induced by lipopolysaccharide(LPS). Methods : To investigate the cytotoxicity of WST, MTT assay was used. The inhibitory effects of inflammatory mediators were confirmed by real-time PCR and DPPH scavenging activity was measured to confirm the antioxidative effect. Results : When the $NF-{\kappa}B$ mRNA expression was inhibited, the levels of COX-2, iNOS, and IL-6 mRNA in the inflammatory response decreased significantly. iNOS is involved in the production of nitric oxide (NO), and it is confirmed that WST inhibits the expression of iNOS mRNA and thus the production of NO. Conclusions : These results suggest that WST can be a therapeutic substance for oxidation and inflammation through elimination of DPPH free radical and inhibition of $NF-{\kappa}B$ activity.

Effects of FLOS LONICERAE Water Extract On Anti-Rheumatiod Arthritis (금은화(金銀花)의 항(抗)류마티즘 효능(效能)에 대한 연구(硏究))

  • Kim, Hee-Soo;Ki, Ho-Pil;Lee, Joon-Suh;Yun, Yong-Gab
    • Herbal Formula Science
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    • v.18 no.2
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    • pp.183-199
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    • 2010
  • Rheumatoid arthritis is characterized by the focal loss of cartilage due to an up-regulation of inflammatory pathways, which produce inflammatory mediators, such as interleukin-1beta(IL-$1{\beta}$), IL-6, tumour necrosis factor alpha(TNF-$\alpha$), prostaglandin, and nitric oxide(NO). We investigated the anti-arthritic effects of water extract from FLOS LONICERAE(FLWE) in vitro and in vivo. Extract inhibited the production of inflammatory mediators(NO, IL-$1{\beta}$, TNF-$\alpha$, and prostaglandin $E_2$) and the expression of inducible NO synthase(iNOS) and cyclooxygenase-2(COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in a dose-dependent manner. FLWE also inhibited TNF-$\alpha$, IL-$1{\beta}$, IL-6, and $PGE_2$ production as well as COX activity in collagen-induced mouse arthritis. Moreover, FLWE significantly suppressed collagen-induced mouse arthritis. These results suggest that FLOS LONICERAE may be useful for therapy against inflammatory immune diseases and rheumatoid arthritis, probably by suppressing the production of inflammatory mediators.

The Role of Nrf2 in Cellular Innate Immune Response to Inflammatory Injury

  • Kim, Ji-Young;Surh, Young-Joon
    • Toxicological Research
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    • v.25 no.4
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    • pp.159-173
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    • 2009
  • Nuclear factor erythroid derived 2-related factor-2 (Nrf2) is a master transcription regulator of antioxidant and cytoprotective proteins that mediate cellular defense against oxidative and inflammatory stresses. Disruption of cellular stress response by Nrf2 deficiency causes enhanced susceptibility to infection and related inflammatory diseases as a consequence of exacerbated immune-mediated hypersensitivity and autoimmunity. The cellular defense capacity potentiated by Nrf2 activation appears to balance the population of $CD4^+$ and $CD8^+$ of lymph node cells for proper innate immune responses. Nrf2 can negatively regulate the activation of pro-inflammatory signaling molecules such as p38 MAPK, NF-${\kappa}B$, and AP-1. Nrf2 subsequently functions to inhibit the production of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloproteinases, COX-2 and iNOS. Although not clearly elucidated, the antioxidative function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the expression of pro-inflammatory mediators.

Effects of Haedokgumhwa-san Water Extracts on LPS-induced Inflammatory Response in Macrophage (해독금화산 물추출물이 LPS로 유도된 대식세포의 염증반응에 미치는 영향)

  • LIM, Jae-Soo;KANG, Ok-Hwa;SEO, Yun-Soo;KWON, Dong-Yeul
    • The Korea Journal of Herbology
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    • v.30 no.5
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    • pp.67-74
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    • 2015
  • Objectives : TheHaedokgumhwa-sanwater extract (HDKHS) is used in Korea, Japan and China as a traditional therapeutic agent to cure an infectious disease. But its study is not enough. Therefore, the present study focused on the elucidation of HDKHS to investigate the anti-inflammatory effects and to established the possible mechanisms involved in its action on LPS-stimulated immune response in murine macrophages.Methods : Inflammatory status was induced by LPS and measured by increasement of inflammatory mediators. LPS induced secretions of NO and PGE2in RAW 264.7 cells were measured using griess reagent and enzyme-linked immunosorbent assay (ELISA) kit respectively. production of IL-6 was examined using ELISA kit and expression of IL-6 mRNA was measured by RT-PCR method. To investigate the effects of HDKHS on inflammatory mediators, such as iNOS, COX-2 and MAPKs, western blot and RT-PCR were performed.Results : HDKHS significantly reduced production of NO and PGE2 which were induced by LPS. Also, activation of IL-6 was reduced both protein and mRNA levels. The expressions of inflammatory mediator include iNOS and COX-2 were decreased by pretreatment with HDKHS. futhermore The result showed HDKHS down-regulate the LPS induced phosphorylation of ERK 1/2, one of the MAPK family, which is considered as a main regulator of transmission from pathogens to nucleus of immune cells.Conclusions : Our results suggest that the anti-inflammatory properties of HDKHS may stem from the inhibition of pro-inflammatory mediators via suppression of initiation of inflammatory response by inhibiting MAPKs signaling pathways.

Sputum Inflammatory Mediators Are Increased in Aspergillus fumigatus Culture-Positive Asthmatics

  • Ghebre, Michael A;Desai, Dhananjay;Singapuri, Amisha;Woods, Joanne;Rapley, Laura;Cohen, Suzanne;Herath, Athula;Wardlaw, Andrew J;Pashley, Catherine H;May, Richard;Brightling, Chris E
    • Allergy, Asthma & Immunology Research
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    • v.9 no.2
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    • pp.177-181
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    • 2017
  • Aspergillus fumigatus sensitization and culture in asthma are associated with disease severity and lung function impairment, but their relationship with airway inflammation is poorly understood. We investigated the profile of 24 sputum inflammatory mediators in A. fumigatus culture-positive or-negative moderate-to-severe asthmatics. Fifty-two subjects were recruited from a single center. A. fumigatus was cultured from 19 asthmatics. Asthma control, symptom score, lung function, and sputum cell count were not significantly different between the asthmatics with and without a positive A. fumigatus culture. All of the sputum mediators were numerically increased in subjects with a positive versus negative sputum A. fumigatus culture. Sputum TNF-R2 was significantly elevated (P=0.03) and the mediator that best distinguished A. fumigatus culture-positive from culture-negative subjects (receiver-operator characteristic area under the curve 0.66 [95% CI: 0.51 to 0.82, P=0.045]). A. fumigates-positive culture in moderate-to-severe asthma is associated with increased inflammatory sputum mediators.

Anti-Inflammatory Effect of Aqueous Extract of Scolopendrae Corpus in RAW 264.7 Cells (마우스 대식세포주인 RAW 264.7 세포에서 오공(蜈蚣)의 항염증 효과)

  • Jo, Il-Joo;Choi, Mee-Ok;Park, Min-Cheol;Song, Ho-Joon;Park, Sung-Joo
    • The Korea Journal of Herbology
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    • v.26 no.3
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    • pp.23-29
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    • 2011
  • Objective : The purpose of this study was to investigate the anti-inflammatory effects of aqueous extract from Scolopendrae Corpus (SC) on lipopolysaccharide (LPS)-induced inflammatory response. Methods : To evaluate the anti-inflammatory effects of SC, we examined the inflammatory mediators such as nitric oxide (NO) and pro-inflammatory cytokines (TNF-a, inteleukin (IL)-$1{\beta}$ and IL-6) on RAW 264.7 cells. We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and inhibitory kappa B a ($I{\kappa}$-Ba) using western blot. Furthermore, we also investigated the effect of SC on LPS-induced endotoxin shock. Results : Extract from SC itself had not any cytotoxic effect in RAW 264.7 cells. Aqueous extract from SC inhibited LPS-induced NO production and iNOS expression. SC pre-treatment also inhibited IL-$1{\beta}$, IL-6 production in RAW 264.7 cells. To investigate inhibitory effects of SC on inflammatory mediators, activation of MAPKs was examined. SC inhibited the phosphorylation of p38 kinases (p38), c-Jun $NH_2$-terminal kinase (JNK) and also the degradation of $I{\kappa}$-$B{\alpha}$ in RAW 264.7 cells stimulated with LPS. Furthermore, SC administration reduced LPS-induced endotoxin shock. Conclusion : SC down-regulated LPS-induced production of inflammatory mediators through inhibition of activation of p38, JNK and degradation of $I{\kappa}$-$B{\alpha}$. Taken together, our results suggest that SC may be a beneficial drug against inflammatory diseases such as sepsis.

Anti-inflammatory effects of proanthocyanidin-rich red rice extract via suppression of MAPK, AP-1 and NF-κB pathways in Raw 264.7 macrophages

  • Limtrakul, Pornngarm;Yodkeeree, Supachai;Pitchakarn, Pornsiri;Punfa, Wanisa
    • Nutrition Research and Practice
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    • v.10 no.3
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    • pp.251-258
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    • 2016
  • BACKGROUND/OBJECTIVES: Several pharmacological properties of red rice extract have been reported including anti-oxidant, anti-tumor, and reduced cancer cell invasion. This study was conducted to evaluate the anti-inflammatory effects of red rice extract on the production of inflammatory mediators in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages. MATERIALS/METHODS: Pro-inflammatory cytokines including tumor necrosis factor-${\alpha}$ and interleukin-6 were determined by ELISA and cyclooxygenase-2 and inducible nitric oxide synthase expression was evaluated using western blot analysis. In addition, the signaling pathway controlling the inflammatory cascade such as nuclear factor kappa B ($NF-{\kappa}B$), activator proteins-1 (AP-1), and mitogen-activated protein kinase (MAPK) was determined. RESULTS: Our results showed that red rice polar extract fraction (RR-P), but not non-polar extract fraction, inhibited interleukin-6, tumor necrosis factor-${\alpha}$, and nitric oxide production in LPS-induced Raw 264.7 cells. RR-P also reduced the expression of inflammatory enzymes, inducible nitric oxide synthase, and cyclooxygenase-2. In addition, activation of AP-1 and $NF-{\kappa}B$ transcription factor in the nucleus was abrogated by RR-P. RR-P inhibited the phosphorylation of extracellular signaling-regulated kinase 1/2, c-Jun NH2-terminal kinase, and p38 MAPK signaling responsible for the expression of inflammatory mediators in LPS-stimulated Raw 264.7 cells. Based on chemical analysis, high amounts of proanthocyanidin and catechins were detected in the RR-P fraction. However, only proanthocyanidin reduced $NF-{\kappa}B$ and AP-1 activation in LPS-activated Raw 264.7 cells. CONCLUSION: These observations suggest that the anti-inflammatory properties of RR-P may stem from the inhibition of pro-inflammatory mediators via suppression of the AP-1, $NF-{\kappa}B$, and MAPKs pathways.