• Title/Summary/Keyword: iNOS$TNF-{\alpha}$

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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.

Ethanol-Heated Processed Scutellariae Radix Improve Inflammatory Response through an Inhibitory Effect against Oxidative Stress in Mice with the Lipopolysaccharide-induced Intestine Injury of Mice (LPS로 유발한 장염증 모델에 대한 주초황금의 항산화 조절 및 장염증 개선 효과)

  • Shin, SungHo;Shin, YuOck;Lee, JooYoung;Lee, AhReum;Kim, MinYeong;Park, ChanHum;Seo, BuIl;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.30 no.4
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    • pp.81-88
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    • 2015
  • Objectives : The aim of present study was to evaluate the beneficial effect of Scutellariae Radix (SR) and Scutellariae Radix EtOH-heated at 200℃ (SR200) using lipopolysaccharide (LPS) treated intestine of mice.Methods : Extract of SR and SR200 were orally administrated. Their effects were compared with vehicletreated LPS and normal groups. Subsequently, we measured reactive oxygen species (ROS) and nitric oxide in the serum and western blotting in the intestine.Results : The average weight in LPS treated (Vehicle) group was lowered significantly compare to that in non-treated normal group and this weight loss in the vehicle group was effectively prevented by the administration of SR and SR200 respectively. The increased oxidative stress biomarker levels such as reactive oxygen species (ROS) and nitric oxide (NO) in the serum was markedly decreased by treated with SR200. The decreased levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) induced by LPS injection were significantly restored by both SR and SR200 treatment. Moreover, increased inflammatory mediators and cytokines such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in the LPS treated vehicle mice were significantly decreased through down-regulation c-JUN through reduction of oxidative stress.Conclusions : SR and SR200 could have benefit effect through down-regulation of abnormal oxidative stress in LPS induced intestine injury mice. Moreover, The anti-inflammatory activity of SR200 extract was better than SR extract in the LPS induced intestine injury mice.

Protective Effects of a Lycium chinense Ethanol Extract through Anti-oxidative Stress on Acute gastric lesion mice (급성 위염 유발 마우스 동물 모델에서 구기자(枸杞子) 에탄올 추출물의 위점막 손상 보호 효과)

  • Lee, AhReum;Lee, JooYoung;Kim, MinYeong;Shin, Mi-Rae;Shin, SungHo;Seo, BuIl;Kwon, OJun;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.30 no.6
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    • pp.63-68
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    • 2015
  • Objectives : Gastric lesions affect many people around the world and their development are results of the imbalance between destructive and protective factors in the gastric mucosa. Lycium chinense has been widely used as a traditional Korean medicine, it was recently reported that they have potent anti-inflammatory effects in chronic hepatitis models. Therefore, this study aimed to investigate the anti-inflammatory activity of Lycium chinense extract (LCE) on HCl-Ethanol induced gastric lesion mice.Methods : The ICR mice were divided randomly into five groups of six animals each. Group A was normal mice, and group B was treated orally with 0.5 ml 150 mM HCl-60% Ethanol. Mice in group C and D were pre-treatment of LCE (100 mg/kg and 200 mg/kg bodyweight, p.o before HCl/ethanol treatment) and group E was orally administered sucralfate (10 mg/kg).Results : 150mM HCl/60% ethanol-induced gastric mucosal injury mice were ameliorated mucosal damage upon histological evaluation by treatment of LCE. Pre-treatment of LCE attenuated reactive oxidative species (ROS) and produces peroxynitrite (ONOO-) in stomach tissues. As results of stomach protein analyses, LCE effectively reduce inflammatory-related factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) in gastric lesion mice. In addition, nuclear factor kappa B (NF-κB) and inhibitor of phosphorylation of nuclear factor kappa B (p-IκB) were down-regulated in LCE-administrated gastric lesion mice.Conclusions : Our discovery supports that the therapeutic activity of LCE ameliorate the development of gastric lesion via suppressing the oxidative stress and gastric partial inflammation induced by 150 mM HCl/60% ethanol.

Betulinic Acid Inhibits LPS-Induced MMP-9 Expression by Suppressing NF-kB Activation in BV2 Microglial Cells

  • Lee, Jae-Won;Choi, Yong-Joon;Kim, Song-In;Lee, Sue-Young;Kang, Sang-Soo;Kim, Nam-Ho;Kwon, Yong-Soo;Lee, Hee-Jae;Chun, Wan-Joo;Kim, Sung-Soo
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.431-437
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    • 2011
  • Aberrant activation of microglia has been reported to cause neuronal damages by releasing a variety of pro-inflammatory cytokines. Besides where microglia become active, damages have been also observed in remote places, which is considered due to the migration of activated microglia. Therefore, an agent that could suppress abnormal activation of microglia and their subsequent migration might be valuable in activated microglia-related brain pathologies. The objective of the present study was to evaluate anti-inflammatory effects of betulinic acid on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of betulinic acid significantly attenuated LPS-induced NO production and protein expression of iNOS. Betulinic acid also significantly suppressed LPS-induced release and expression of cytokines such as TNF-${\alpha}$ and IL-$1{\beta}$. Furthermore, betulinic acid significantly uppressed LPS-induced MMP-9 expression, which has been suggested to play an important role in the migration of activated microglia. In order to understand the possible mechanism by which betulinic acid suppresses LPS-induced cytokine production and migration of microglia, the role of NF-kB, a major pro-inflammatory transcription factor, was examined. Betulinic acid significantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB upon LPS stimulation was significantly suppressed with betulinic acid. Taken together, the present study for the first time demonstrates that betulinic acid possesses anti-inflammatory activity through the suppression of nuclear translocation of NF-kB in BV2 microglial cells.

Evaluation on Anti-oxidant Activity and Anti-inflammatory Effects for the New Formulation of Gamisoyosan (가미소요산의 새로운 제형에 대한 항산화 활성 및 항염증 효능평가)

  • Choi, Hye-Min;Kim, Se-Jin;Kim, In-Su;Lee, Ji-Beom;Kim, Jong-Beom;Moon, Sung-Ok;Lee, Hwa-Dong
    • The Korea Journal of Herbology
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    • v.31 no.6
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    • pp.1-9
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    • 2016
  • Objectives : Gamisoyosan (GMS) is a useful prescription for treating insomnia, dysmenorrhea and infertility induced by a stress. Also, GMS has been used traditionally to improve systemic circulation and biological energy production. The purpose of this study was to assess the anti-oxidant activity and anti-inflammatory effects of Gamisoyosan Formulation (Soft extract, GMS-SE). Methods : The biological activities such as anti-oxidant and anti-inflammatory effects were measured through cell line-based in vitro assay. We investigated the anti-oxidant properties of GMS-SE on the 1,1-diphenyl-2-picryhydrazyl (DPPH) radical, contents of total flavonoid and polyphenol. GMS-SE compared to butyl hydroxy anizole (BHA). Furthermore, based on this result the anti-inflammatory effects of GMS-SE have verified by mechanism from LPS- treated Raw264.7 macrophages. Results : The anti-oxidant activities of GMS-SE increased markedly, in a dose-dependent manner. The GMS-SE showed significant scavenging activity (GMS-SE $500{\mu}g/m{\ell}$ : $32.77{\pm}1.65%$, GMS-SE $1000{\mu}g/m{\ell}$ : $45.06{\pm}1.04%$ and BHA $100{\mu}g/m{\ell}$ : $39.25{\pm}2.41%$ for DPPH assay). and, The total phenolic compound and flavonoids contents of GMS-SE were $73.93{\pm}6.87{\mu}g/mg$ and $698.75{\pm}6.78{\mu}g/mg$. GMS-SE which is LPS has diminished in the LPS-induced release of inflammatory mediators (NO, iNOS, COX2 and PGE2) and pro-inflammatory cytokines (TNF-${\alpha}$, IL-6 and IL-$1{\beta}$) from the RAW264.7 macrophages. Moreover, GMS-SE inhibited the activation of phosphorylation of p38 and ERK MAPKs by induced LPS. Conclusion : The present results indicate that GMS-SE has an anti-oxidant and anti-inflammatory properties, therefore may be beneficial in diseases which related to oxidative stress-mediated inflammatory disorders.

Gastroprotective Activity of Curcumae Longae Rhizoma against Gastric Ulcer in Mice (위궤양 유발 마우스모델에서 강황(薑黃) 추출물의 위 보호 효과)

  • Oh, Min Hyuck;Kim, Min Ju;Shin, Mi-Rae;Park, Hae-Jin;Seo, Bu-Il;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.35 no.3
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    • pp.17-24
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    • 2020
  • Objectives : The objective of this study was to evaluate the gastric protective effect of Curcuma Longae Rhizoma (CLR) in 150 mM HCl/60% ethanol induced gastric ulcer (GU) in mice. Methods : Forty ICR mice were divided into five groups (n=8/Group): Nor group; Normal, Veh group; GU control, SC group; GU + sucralfate 10 mg/kg, CL; GU + CLR 30% ethanol extract 100 mg/kg, CH group; GU + CLR 30% ethanol extract 200 mg/kg. Then, mice were orally administered with 150 mM HCl/60% ethanol and caused GU. After 1 hr, mice were sacrificed, and blood and stomach tissue were collected. Results : CLR showed significance scavenging effects in 1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging activities (DPPH IC50; 78.18 ± 0.60 ㎍/㎖, ABTS IC50; 55.91 ± 1.86 ㎍/㎖). CLR significance reduce inflammatory-related factors such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin-6 (IL-6) via nuclear factor kappa B (NF-κB) inactivation. In addition, the activation of nuclear factor erythroid2-related factor 2 (Nrf2) significantly led to up-regulation of anti-oxidant enzymes including factors heme oxygenase-1 (HO-1), super oxide dismutase (SOD), and glutathione peroxidase-1/2 (GPx-1/2). Conclusions : Our discovery provides that CLR possesses anti-oxidant and anti-inflammatory effects. Hence, CLR may ameliorate the development of gastric ulcer though the inhibition of NF-κB inflammatory pathway and the elevation of Nrf2 anti-oxidant pathway.

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.

Anti-inflammatory effects of Ishige sinicola ethanol extract in LPS-induced RAW 264.7 cell and mouse model (LPS로 유도된 RAW 264.7 Cell과 마우스 모델에 대한 넓패(Ishige sinicola) 에탄올 추출물의 항염증 효과)

  • Kim, Ji-Hye;Kim, Min-Ji;Kim, Koth-Bong-Woo-Ri;Park, Sun-Hee;Cho, Kwang-Su;Kim, Go-Eun;XU, Xiaotong;Lee, Da-Hye;Park, Ga-Ryeong;Ahn, Dong-Hyun
    • Food Science and Preservation
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    • v.24 no.8
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    • pp.1149-1157
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    • 2017
  • Inflammation is the first response of the immune system to infection or irritation in our body. The use of medicinal plants has been widely applied as an alternative source for drug development. One of marine natural resources, the anti-inflammatory effect of Ishige sinicola ethanol extract (ISEE), was evaluated by using LPS-induced RAW 264.7 cell and mice model. As a result, the production of nitric oxide (NO) and pro-inflammatory cytokines (IL-6, IL-$1{\beta}$, TNF-${\alpha}$) were inhibited with increasing concentration of ISEE without any cytotoxicity. Furthermore, ISEE suppressed the expression of not only inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-${\kappa}B$) p65, and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. In mice ear edema test, the formation of edema was reduced at the highest dosage of ISEE and the reduction of the number of infiltrated mast cells was observed in histological analysis. These results indicate that ISEE has a potent anti-inflammatory activity and can be used as a pharmaceutical material for many kinds of inflammatory disease.

Anti-inflammatory effect of barley leaf ethanol extract in LPS-stimulated RAW264.7 macrophage (LPS로 자극한 RAW264.7 대식세포에서 보리순 에탄올 추출물의 항염증 효과)

  • Kim, Mee-Kyung;Kim, Dae-Yong
    • Food Science and Preservation
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    • v.22 no.5
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    • pp.735-743
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    • 2015
  • This study investigated the anti-inflammatory activity of barley leaf extract in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and hairless mice. Pre-treatment with barley leaf extract significantly inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-II (COX-II) in a dose-dependent manner in LPS-stimulated RAW264.7 cells. Barley leaf extract also significantly inhibited the secretion of inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) were strongly suppressed by barley leaf extract in LPS-stimulated cells. In hairless mice, barley extract significantly decreased the pathological phenotypes of contact dermatitis, such as erythema, edema, and scabs. These results indicate that barley leaf extract has an anti-inflammatory effect and therefore a possible role in the treatment of inflammatory diseases or in functional cosmetics.

Anti-neuroinflammatory Effect of Teleogryllus emma Derived Teleogryllusine in LPS-stimulated BV-2 Microglia (BV-2 미세아교세포에서 왕귀뚜라미 유래 Teleogryllusine의 신경염증 억제 효과)

  • Seo, Minchul;Shin, Yong Pyo;Lee, Hwa Jeong;Baek, Minhee;Lee, Joon Ha;Kim, In-Woo;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • v.30 no.11
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    • pp.999-1006
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    • 2020
  • The suppression of neuroinflammatory responses in microglial cells, well known as the main immune cells in the central nervous system (CNS), are considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Teleogryllus emma is widely consumed around the world for its broad-spectrum therapeutic effect. In a previous work, we performed transcriptome analysis on T. emma in order to obtain the diversity and activity of its antimicrobial peptides (AMPs). AMPs are found in a variety of species, from microorganisms to mammals. They have received much attention as candidates oftherapeutic drugs for the treatment of inflammation-associated diseases. In this study, we investigated the anti-neuroinflammatory effect of Teleogryllusine (VKWKRLNNNKVLQKIYFVKI-NH2) derived from T. emma on lipopolysaccharide (LPS) induced BV-2 microglia cells. Teleogryllusine significantly inhibited nitric oxide (NO) production without cytotoxicity, and reducing pro-inflammatory enzymes expression such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, Telegryllusine also inhibited the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) through down-regulation of the mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathway. These results suggest that T. emma-derived Teleogryllusine could be a good source of functional substances that prevent neuroinflammation and neurodegenerative diseases.