• Title/Summary/Keyword: Anti-inflammatory responses

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Inhibitory Effect of Kamisopunghwalhyeol-tang (Jiaweishufenghuoxie-tang) on Inflammatory Cytokine Production and $NF-{\kappa}B$ and AP-1 Activation in Cultured Humau Fibroblast-like Synoviocytes (가미속풍활형탕이 human fibroblast-like synoviocytes 내 염증 유발 cytokine과 전사인자에 미치는 영향)

  • 양동원;오민석;김동희
    • The Journal of Korean Medicine
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    • v.24 no.3
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    • pp.84-95
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    • 2003
  • Objective : This study was carried out to investigate the effects of Kamisopunghwalhyeol-tang (Jiaweishujenghuoxie-tang; Kami-SPHHT) on the immunity responses of the Synoviocytes isolated from the patients on rheumatoid arthritis. Methods : Cells were stimulated by $Interleukin-1{\beta}$ and Tumor Necrosis $Factor-{\alpha}$ in the presence or absence of Kami-SPHHT, and then induced cytokine mRNA levels were determined by RT-PCR and real-time quantitative RT-PCR. Results : Levels of $IL-1{\beta},{\;}IL-6,{\;}TNF-{\alpha}$, COX-2, and NOS II mRNA expressions significantly decreased in Kami-SPHHT treated cells compared to non-treated control cells. Also, DNA-binding activity of $NF-{\kappa}B$ and AP-l decreased in Kami- SPHHT treated hFLSs. Conclusion : These results suggest that Kami-SPHHT may be involved in anti-inflammatory reactions by inducing cytokine gene expression in synoviocytes, and further in vivo examination on its efficacy can provide potential application for the treatment of rheumatoid arthritis.

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Effects of Dioscorea daemona Roxb. Stem Extract on the Inflammatory Responses, Antioxidant System and Lipid Levels in Vivo and the Production of Inflammatory Mediators in RAW264.7 Cells (Dioscorea daemona Roxb. (Stem) 추출물이 Rat의 염증반응 및 항산화 체계에 미치는 영향과 RAW264.7 세포주의 염증성 매개물 생성에 미치는 영향)

  • Choi Eun-Mi;Koo Sung-Ja
    • Journal of the East Asian Society of Dietary Life
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    • v.15 no.6
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    • pp.707-716
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    • 2005
  • 본 연구에서는 다양한 동물 모델을 사용하여 Dioscorea daemona Roxb. 줄기 메탄을 추출물(DD)의 항염증 활성을 측정하였으며 DD가 생체내에서 항산화 체계의 변화를 유도할 수 있는지도 살펴보았다. DD를 200mg/kg용량으로 3주간 경구투여하였을 때 동물실험모델에서 항염증 및 type IV 알레르기 억제 효과를 나타내었으며 혈청의 Catalase 활성, 지질 과산화, TG 및 HDL cholesterol 수치가 영향을 받았다. DD와 이를 클로로포름과 부탄올로 순차적으로 분획하여 얻은 fraction이 lipopolysaccharide(LPS)로 유도한 RAW264.7 대식세포주의 nitric oxide(NO), prostaglandin $E_2(PGE_2)$, tumor necrosis $factor-\alpha(TNF-\alpha)$, interleukin 6(IL6)의 생성을 억제하는지도 연구하였다. DD와 그 분획물들은 $4\~100{\mu}g/mL$ 농도에서 세포 독성을 나타내지 않고 LPS가 유도한 RAW264.7 세포주의 NO, $TNF-\alpha$, IL-6 생성을 억제하였다. LPS가 유도한 $PGE_2$ 생성은 DD의 클로로포름 분획에서 유의적으로 감소하였다(p<0.05). 따라서 Dioscorea daemona 추출물은 대식세포의 염증성 매개물의 억제를 통하여 항염증 활성을 나타내는 것으로 사료된다.

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Dendrobium moniliforme Stem Extract Inhibits Lipoteichoic Acid-Induced Inflammatory Responses by Upregulation of Heme Oxygenase-1

  • Lee, Young Ji;Kim, Ji-Hee;Kim, YoungHee
    • Journal of Microbiology and Biotechnology
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    • v.28 no.8
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    • pp.1310-1317
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    • 2018
  • The stems of Dendrobium moniliforme have been used in traditional herbal medicine for the treatment of fever and lack of body fluid in Korea. In this study, we investigated anti-inflammatory effects of the aqueous extract of D. moniliforme stems (DM) in response to lipoteichoic acid (LTA), a major constituent of the cell wall of Gram-positive bacteria. DM inhibited LTA-induced expression of a pro-inflammatory mediator inducible nitric oxide synthase (iNOS) in the murine macrophages. And DM induced expression of heme oxygenase-1 (HO-1) at the transcriptional level. Conversely, the knockdown of HO-1 expression by siRNA markedly reversed the inhibitory effects of DM on LTA-induced iNOS expression. We also demonstrated that nuclear translocation of Nrf2 was increased following treatment with DM. In addition, DM-mediated Nrf2 activation and HO-1 expression were suppressed by PI3K/Akt and p38 inhibitors; treatment with DM also resulted in phosphorylation of Akt and p38. These results suggest that DM inhibits the expression of iNOS in LTA-stimulated macrophages, and that these effects are mediated by the upregulation of HO-1 expression via PI3K/Akt/p38-Nrf2 signaling.

Effect of Methyl Gallate on 1-Nitropyrene-Induced Keratinocyte Toxicity in a Human and Canine Skin Model

  • Lee, Woo Jin;Kim, Min Jeong;Choi, Hyun-Wook;Lee, Jeong Jae;Jung, Sung Keun
    • Journal of Microbiology and Biotechnology
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    • v.32 no.7
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    • pp.869-876
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    • 2022
  • The skin, which is the largest organ of the human body, is in direct contact with pollutants in the surrounding atmosphere. Meanwhile, 1-nitropyrene (1-NP), the most abundant nitro-polycyclic aromatic hydrocarbon found in particulate matter, is known to have carcinogenic effects; however, studies on its toxicity in human and canine skin are still needed. In this study, we investigated 1-NP-induced apoptosis and inflammatory pathways in HaCaT cells. In addition, we also measured the cytoprotective effect of methyl gallate (MG), which is widely distributed in medicinal and edible plants and is well known for its anti-inflammatory and antioxidant properties. MG inhibited 1-NP-induced cell death and apoptosis pathways, including the cleavage of PARP and activation of caspase-3, -7, and -9. MG also suppressed 1-NP-induced COX-2 expression and phosphorylation of mitogen-activated protein kinases (MAPKs) and MAPK kinases (MAPKKs). Our findings suggest that 1-NP induces skin toxicity in human and canine through apoptosis and inflammatory responses, and moreover, that this can be prevented by treatment with MG.

NRF2 activation by 2-methoxycinnamaldehyde attenuates inflammatory responses in macrophages via enhancing autophagy flux

  • Kim, Bo-Sung;Shin, Minwook;Kim, Kyu-Won;Ha, Ki-Tae;Bae, Sung-Jin
    • BMB Reports
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    • v.55 no.8
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    • pp.407-412
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    • 2022
  • A well-controlled inflammatory response is crucial for the recovery from injury and maintenance of tissue homeostasis. The anti-inflammatory response of 2-methoxycinnamaldehyde (2-MCA), a natural compound derived from cinnamon, has been studied; however, the underlying mechanism on macrophage has not been fully elucidated. In this study, LPS-stimulated production of TNF-α and NO was reduced by 2-MCA in macrophages. 2-MCA significantly activated the NRF2 pathway, and expression levels of autophagy-associated proteins in macrophages, including LC3 and P62, were enhanced via NRF2 activation regardless of LPS treatment, suggesting the occurrence of 2-MCA-mediated autophagy. Moreover, evaluation of autophagy flux using luciferase-conjugated LC3 revealed that incremental LC3 and P62 levels are coupled to enhanced autophagy flux. Finally, reduced expression levels of TNF-α and NOS2 by 2-MCA were reversed by autophagy inhibitors, such as bafilomycin A1 and NH4Cl, in LPS-stimulated macrophages. In conclusion, 2-MCA enhances autophagy flux in macrophages via NRF2 activation and consequently reduces LPS-induced inflammation.

Identification of the Plant Part of Gleditsia sinensis that Activates Nrf2, an Anti-oxidative Transcription Factor (조협의 부위에 따른 항산화 전사인자 Nrf2 활성 효과)

  • Choi, Jiyeon;Kim, Kyun Ha;Choi, Jun Yong;Han, Chang Woo;Ha, Ki Tae;Jeong, Han-Sol;Joo, Myungsoo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.28 no.3
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    • pp.303-309
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    • 2014
  • The fruit of Gleditsia sinensis has been extensively used as a key ingredient of an herbal remedy for the treatment of various inflammatory diseases in traditional Korean Medicine. However, the reason of using the fruit of G. sinensis for the remedy is unclear. Since Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key anti-inflammatory transcription factor, which is activated by the fruit of G. sinesis, we examined whether other plant parts of G. sinensis are also capable of suppressing inflammatory responses by activating Nrf2. Water extracts of various parts of G. sinensis were prepared and tested for Nrf2 activation by reporter assay and western blot analysis. Our results show that the hull of G. sinensis is the most potent in activating Nrf2. Sequential organic solvent extraction of the hull show that all the fractions had a higher potency in activating Nrf2 than the water extract, albeit differential degrees. The hull originated from Korea in general activated Nrf2 strongly compared to that of China. Chloroform fraction of the hull was further examined, showing that the fraction induced nuclear localization of Nrf2, indicative of activated Nrf2, and Nrf2-dependent gene expression including NAD(P)H dehydrogenase quinone 1 (NQO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and heme oxygenase - 1 (HO-1). Therefore, our results show that, among other plant parts examined in this study, the hull of G. sinensis is the most potent, providing the experimental basis for the use of the hull of G. sinensis as an active ingredient for an anti-inflammatory remedy.

Effects of a Tetramethoxyhydroxyflavone on the Expression of Inflammatory Mediators in LPS-Treated Human Synovial Fibroblast and Macrophage Cells

  • Yoon, Do-Young;Cho, Min-Chul;Kim, Jung-Hee;Kim, Eun-Jin;Kang, Jeong-Woo;Seo, Eun-Hee;Shim, Jung-Hyun;Kim, Soo-Hyun;Lee, Hee-Gu;Oh, Goo-Taeg;Hong, Jin-Tae;Park, Joo-Won;Kim, Jong-Wan
    • Journal of Microbiology and Biotechnology
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    • v.18 no.4
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    • pp.686-694
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    • 2008
  • The inhibitory effects of 5,6,3',5'-tetramethoxy 7,4'-hydroxyflavone (labeled as p7F) were elucidated on the productions of proinflammatory cytokines as well as inflammatory mediators in human synovial fibroblasts and macrophage cells. p7F inhibited IL-1${\beta}$ or TNF-${\alpha}$ induced expressions of inflammatory mediators (ICAM-1, COX-2, and iNOS). p7F also inhibited LPS-induced productions of nitric oxide and prostaglandin $E_2$ in RAW 264.7 cells. In order to investigate whether p7F would inhibit IL-1 signaling, p7F was added to the D10S Th2 cell line (which is responsive to only IL-1${\beta}$ and thus proliferates), revealing that p7F inhibited IL-1${\beta}$-induced proliferation of D10S Th2 cells in a dose-response manner. A flow cytometric analysis revealed that p7F reduced the intracellular level of free radical oxygen species in RAW 264.7 cells treated with hydrogen peroxide. p7F inhibited IkB degradation and NF-${\kappa}$B activation in macrophage cells treated with LPS, supporting that p7F could inhibit signaling mediated via toll-like receptor. Taken together, p7F has inhibitory effects on LPS-induced productions of inflammatory mediators on human synovial fibroblasts and macrophage cells and thus has the potential to be an anti-inflammatory agent for inhibiting inflammatory responses.

Respiratory Protective Effect of Salvia plebeia R. Br. Extracts against Ambient Particulate Matter-induced Airway Inflammation (미세먼지 유도 기도염증에 대한 배암차즈기 추출물의 호흡기 보호 효과)

  • Song, Hyeongwoo;Ji, Kon Young;Kim, Bok Kyu;Yang, Won Kyung;Han, Chang Kyun;Shin, Han Jae;Park, Yang Chun;Hwang, Ji Sook;Kang, Hyung Sik;Kim, Seung Hyung
    • Korean Journal of Medicinal Crop Science
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    • v.25 no.5
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    • pp.269-281
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    • 2017
  • Background: Small particles increase airway inflammation upon reaching the alveoli. Here, we investigated the protective or therapeutic effects of Salvia plebeia R. Br. (SP_R) extracts on airway inflammation. Methods and Results: To investigate the anti-inflammatory activity of SP_R extracts, we measured their inhibitory effect on the production of reactive oxygen species (ROS) expression of inflammatory mediators, and immune cell infiltration in MH-S alveolar macrophage cells and in the ambient particulate matter (APM)-exposed airway inflammation mice model. The SP_R extracts inhibited the production of ROS and expression of IL-4, IL-10, IL-15, and IL-17A mRNA in APM-stimulated MH-S cells. Oral administration of SP_R extracts suppressed APM-induced inflammatory symptoms, such as high alveolar wall thickness, excess collagen fibers, decreased mRNA expression of chemokines (Ccr9, Ccl5, Ccr3), inflammatory cytokines (IL-15, TNF-${\alpha}$), and IL-4 Th2 cytokine in the lung. The SP_R extracts also inhibited ROS production, granulocyte ($CD11b^+Gr-1^+$) infiltration, IL-17A, TNF-${\alpha}$, macrophage inflammatory protein (Mip-2), and chemokine (C-X-C motif) ligand 1 (Cxcl-1) production in the airway. The specific compounds in the SR-R extracts that mediate the anti-inflammatory effects were identified. Conclusions: In this study, SP_R extracts effectively inhibited airway inflammatory responses, such as ROS production and granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines.

Lonicerae Flos Inhibits Cigarette-induced Lung Inflammatory Responses in Animal Model of Chronic Obstructive Pulmonary Disease

  • Jung, Kyung-Hwa;Lee, Kye Seok;Kim, Youngeun;Park, Soojin;Hong, Moochang;Shin, Minkyu;Bae, Hyunsu
    • The Journal of Korean Medicine
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    • v.34 no.2
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    • pp.10-19
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    • 2013
  • Objectives: In the present study, we evaluate the anti-inflammatory effect of Lonicerae Flos on cigarette-induced lung inflammatory responses in animal model of chronic obstructive pulmonary diseases (COPD). Methods: To inspect the effects of Lonicerae Flos, we evaluated Lonicerae Flos functions in vivo including immune cell profiles in bronchoalveolar lavage (BAL) fluid, cytokine production and tissue morphological changes. Results: Lonicerae Flos significantly inhibited immune cell infiltrations into the BAL fluid (neutrophils, macrophages, lymphocytes). TNF-${\alpha}$, and interleukin-6 (IL-6) were substantially decreased in the BAL fluid of Lonicerae Flos-treated mice compared with cigarette-exposed control mice. In addition, the hypertrophy of goblet cells in the epithelial cells was reduced in both Lonicerae Flos- and roflumilast-treated mice. Conclusions: The results of this study provide evidence that treatment with Lonicerae Flos exerts strong therapeutic effects against cigarette-induced lung inflammation in vivo. Therefore, this herbal medicine may represent a novel therapeutic agent for lung inflammation in general, as well as a specific agent for the treatment of COPD.

Analgesic Effects of Intrathecal Curcumin in the Rat Formalin Test

  • Han, Yong-Ku;Lee, Seong-Heon;Jeong, Hye-Jin;Kim, Min-Sun;Yoon, Myung-Ha;Kim, Woong-Mo
    • The Korean Journal of Pain
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    • v.25 no.1
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    • pp.1-6
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    • 2012
  • Background: Curcumin has been reported to have anti-inflammatory, antioxidant, antiviral, antifungal, antitumor, and antinociceptive activity when administered systemically. We investigated the analgesic efficacy of intrathecal curcumin in a rat model of inflammatory pain. Methods: Male Sprague Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, $50{\mu}l$) into the hind paw. Curcumin doses of 62.5, 125, 250, and $500{\mu}g$were delivered through an intrathecal catheter to examine the flinching responses. The $ED_{50}$ values (half-maximal effective dose) with 95% confidence intervals of curcumin for both phases of the formalin test were calculated from the dose-response lines fitted by least-squares linear regression on a log scale. Results: In rats with intrathecal administration of curcumin, the flinching responses were significantly decreased in both phases. The slope of the regression line was significantly different from zero only in phase 2, and the $ED_{50}$ value (95% confidence interval) of curcumin was $511.4{\mu}g$ (23.5-1126.5). There was no apparent abnormal behavior following the administration of curcumin. Conclusions: Intrathecal administration of curcumin decreased inflammatory pain in rats, and further investigation to elucidate the precise mechanism of spinal action of curcumin is warranted.