• Title/Summary/Keyword: NF-IL6

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Interruption of Helicobacter pylori-Induced NLRP3 Inflammasome Activation by Chalcone Derivatives

  • Choi, Hye Ri;Lim, Hyun;Lee, Ju Hee;Park, Haeil;Kim, Hyun Pyo
    • Biomolecules & Therapeutics
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    • v.29 no.4
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    • pp.410-418
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    • 2021
  • Helicobacter pylori causes chronic gastritis through cag pathogenicity island (cagPAI), vacuolating cytotoxin A (VacA), lipopolysaccharides (LPS), and flagellin as pathogen-related molecular patterns (PAMPs), which, in combination with the pattern recognition receptors (PRRs) of host cells promotes the expression and secretion of inflammation-causing cytokines and activates innate immune responses such as inflammasomes. To identify useful compounds against H. pylori-associated gastric disorders, the effect of chalcone derivatives to activate the nucleotide-binding oligomerization domain (NOD)-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome was examined in an H. pylori-infected human monocytic THP-1 cell line in this study. Among the five synthetic structurally-related chalcone derivatives examined, 2'-hydroxy-4',6'-dimethoxychalcone (8) and 2'-hydroxy-3,4,5-trimethoxychalcone (12) strongly blocked the NLRP3 inflammasome in H. pylori-infected THP-1 cells. At 10 μM, these compounds inhibited the production of active IL-1β, IL-18, and caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization, but did not affect the expression levels of NLRP3, ASC, and pro-caspase-1. The interruption of NLRP3 inflammasome activation by these compounds was found to be mediated via the inhibition of the interleukin-1 receptor-associated kinase 4 (IRAK4)/IκBα/NF-κB signaling pathway. These compounds also inhibited caspase-4 production associated with non-canonical NLRP3 inflammasome activation. These results show for the first time that certain chalcones could interrupt the activation of the NLRP3 inflammasome in H. pylori-infected THP-1 cells. Therefore, these chalcones may be helpful in alleviating H. pylori-related inflammatory disorders including chronic gastritis.

Protective Effect of Spatholobi Caulis in Thioacetamide induced Acute Liver Injury of Rat (Thioacetamide로 유발한 간손상 모델에서 계혈등(鷄血藤)의 간보호 효과)

  • Oh, Min Hyuck;Shin, Mi-Rae;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.36 no.2
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    • pp.31-42
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    • 2021
  • Objectives : This study was undertaken to investigate the hepatoprotective effect of Spatholobi Caulis water extract (SC) to thioacetamide (TAA)-induced acute liver injury (ALI) in rats. Methods : The rats were injected intraperitoneally with TAA (200 mg/kg body weight) and orally administered SC (100 or 200 mg/kg b.w.) daily for 3 days. Liver biomarkers were assessed by serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and ammonia levels. Malondialdehyde (MDA) was measured both serum and liver tissue. In addition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, anti-oxidant, and inflammation-related proteins were investigated by western blot analysis. Histological examination further confirmed though hematoxylin and eosin stain. Results : The SC treatment reduced liver function markers like GOT and GPT and also remarkably decreased ammonia level. Moreover, the elevated MDA level in TAA-induced group was significantly reduced by SC treatment. NADPH oxidase expression associated with oxidative stress including NOX2, NOX4, and p47phox markedly inhibited by SC administration. SC treatment exerted anti-oxidant effect through the increase of anti-oxidant enzyme including superoxide dismutase (SOD), Catalase, and heme oxygenase-1 (HO-1). The protein expressions of inflammatory cytokines such as tumor necrosis factor-�� (TNF-��), IL-6, and IL-1�� induced by nuclear factor-kappa B (NF-��B) activation were modulated through blocking the phosphorylation of inhibitor of nuclear factor ��B�� (I��B)��. SC treatment also improved histological alterations. Conclusion : These findings suggested that SC administration may be a potential candidate for the prevention or treatment of ALI.

Anti-inflammatory and antioxidant activities of Sargassum horneri extract in RAW264.7 macrophages

  • Kim, Min Ju;Jo, Hee Geun;Ramakrishna, Chilakala;Lee, Seung-Jae;Lee, Dong-Sung;Cheong, Sun Hee
    • Korean Journal of Exercise Nutrition
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    • v.25 no.4
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    • pp.45-53
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    • 2021
  • [Purpose] In this study, we investigated whether a 70% ethanolic (EtOH) extract of Sargassum horneri had antioxidant and anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated macrophage-like RAW 264.7 cells. [Methods] The proximate composition, fatty acids, amino acids, and dietary fiber of S. horneri, various biologically active compounds, and antioxidant activity were analyzed. [Results] The DPPH and ABTS free radical scavenging activities, as well as the reduction power, of the S. horneri extract used here were significantly increased in a concentration-dependent manner. This indicates that S. horneri contains bioactive compounds, such as phenols and flavonoids, that have excellent antioxidant activity. The cellular viability and metabolic activity results confirmed that the extract had no discernible toxicity at concentrations up to 100 ㎍/mL. The levels of nitrites and cytokines (PGE2, TNF-α and IL-6), which mediate pro-inflammatory effect, were significantly inhibited by treatment with either 50 or 100 ㎍/mL S. horneri extract, whereas that of IL-1β was significantly inhibited by treatment with 100 ㎍/mL of the extract. Similarly, the expression of iNOS and COX-2 proteins also decreased according to 50 or 100 ㎍/mL extract concentrations. NF-κB binding to DNA was also significantly inhibited by treatment with 100 ㎍/mL of extract. [Conclusion] These results suggest that 70% EtOH extracts of S. horneri can relieve inflammation caused by disease or high intensity exercise.

Effects of Pogonatherum paniceum (Lamk) Hack extract on anti-mitochondrial DNA mediated inflammation by attenuating Tlr9 expression in LPS-induced macrophages

  • Rungthip Thongboontho;Kanoktip Petcharat;Narongsuk Munkong;Chakkraphong Khonthun;Atirada Boondech;Kanokkarn Phromnoi;Arthid Thim-uam
    • Nutrition Research and Practice
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    • v.17 no.5
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    • pp.827-843
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    • 2023
  • BACKGROUND/OBJECTIVES: Mitochondrial DNA leakage leads to inflammatory responses via endosome activation. This study aims to evaluate whether the perennial grass water extract (Pogonatherum panicum) ameliorate mitochondrial DNA (mtDNA) leakage. MATERIALS/METHODS: The major bioactive constituents of P. paniceum (PPW) were investigated by high-performance liquid chromatography, after which their antioxidant activities were assessed. In addition, RAW 264.7 macrophages were stimulated with lipopolysaccharide, resulting in mitochondrial damage. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to examine the gene expression and cytokines. RESULTS: Our results showed that PPW extract-treated activated cells significantly decrease reactive oxygen species and nitric oxide levels by reducing the p2phox and iNOS expression and lowering cytokine-encoding genes, including IL-6, TNF-α, IL-1β, PG-E2 and IFN-γ relative to the lipopolysaccharide (LPS)-activated macrophages. Furthermore, we observed that LPS enhanced the mtDNA leaked into the cytoplasm, increasing the transcription of Tlr9 and signaling both MyD88/Irf7-dependent interferon and MyD88/NF-κb p65-dependent inflammatory cytokine mRNA expression but which was alleviated in the presence of PPW extract. CONCLUSIONS: Our data show that PPW extract has antioxidant and anti-inflammatory activities by facilitating mtDNA leakage and lowering the Tlr9 expression and signaling activation.

Effects of PGA-LM on CD4+CD25+foxp3+ Treg Cell Activation in Isolated CD4+ T Cells in NC/Nga Mice (NC/Nga 생쥐에서 분리한 T 세포에서 foxp3+ 세포 활성화에 대한 PGA-LM의 효과)

  • Jang, Soon-Nam;Kim, Kum-Lan;Kang, Sang-Mo
    • Microbiology and Biotechnology Letters
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    • v.37 no.2
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    • pp.160-169
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    • 2009
  • Poly-$\gamma$-glutamic acid ($\gamma$-PGA) was mixed natural flora of Bacillus subtilis, contaminated from cooked soybeans. Also, it was performed to find out the antiallergic activity by using NC/Nga mice, in vitro. The $\gamma$-PGA (PGA-HM : PGA-high molecular weight), Molecular weight 300 kDa, was decomposed and made PGA-LM (PGA-low molecular weight) which has molecular weight below 30 kDa by sonication. Therefore, it was same result between PGA-HM and PGA-LM, and reported PGA-LM as basic result. We found that PGA-LM contains antiallergic efficacy that inhibit B cells and Th2 cells activation from isolated CD4+T cells in NC/Nga atopic dermatitis model mice, and not show a cytotoxicity in the hFCs. To investigate the effects of these PGA-LM in vitro, isolation of splenic B cell and CD4+ T cells in atopic dermatitis mice were used. To elucidate the role of PGA-LM in anti-CD40+ interleukin-4 (IL-4)-mediated B-cell activation, showed that the capacity of B cells to expression IL-$1\beta$, IL-6, and TNF-$\alpha$ mRNA down-regulated, and IL-10 mRNA up-regulation by PGA-LM treatment, but it had no effect on TGF-$\beta$ expression. In addition to CD4+IFN-$\gamma$+ and CD4+CD25+foxp3+, the functions of PGA-LM in the development of the CD4+CD25+foxp3+ and CD4+IFN-$\gamma$+cells, the phenotype and functions of PGA-LM induced CD4+CD25+foxp3+, and CD4+IFN-$\gamma$+cells in CD4+T cells. These results suggested that PGA-LM could change cytokine production and generate CD4+CD25+foxp3+ Tregs in NC/Nga mice, and may be effective for immunotherapy in patients with AD.

Anti-inflammatory Effect of Flavonoids Kaempferol and Biochanin A-enriched Extract of Barnyard Millet (Echinochloa crus-galli var. frumentacea) Grains in LPS-stimulated RAW264.7 Cells (마우스 대식 세포주 RAW264.7에 있어서 LPS처리에 의해 유도되는 염증반응에 대한 식용피(Echinochloa crus-galli var. frumentacea)의 저해효과)

  • Lee, Ji Young;Jun, Do Youn;Yoon, Young Ho;Ko, Jee Youn;Woo, Koan Sik;Woo, Mi Hee;Kim, Young Ho
    • Journal of Life Science
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    • v.24 no.11
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    • pp.1157-1167
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    • 2014
  • In order to compare the anti-inflammatory effects of five selected cereal grains-proso millet, hwanggeumchal sorghum, foxtail millet, barnyard millet, and adlay-the inhibitory activities of 80% ethanol (EtOH) extracts obtained from the individual grains on lipopolysaccharide (LPS)-induced nitric oxide (NO) generation were investigated in RAW264.7 cells. The EtOH extract of barnyard millet (Echinochloa crus-galli var. frumentacea) grains exhibited more potent anti-inflammatory activity than that of the other grains. When the EtOH extract of barnyard millet grains was sequentially fractionated with n-hexane, methylene chloride (MC), ethyl acetate (EtOAc), and n-butanol, the majority of the anti-inflammatory activity was detected in the MC fraction, followed by the EtOAc fraction. Pretreatment with the MC fraction caused downregulation of the expression levels of iNOS- and COX-2-specific transcripts and proteins, as well as proinflammatory cytokine gene transcripts (IL-$1{\beta}$, IL-6, and TNF-${\alpha}$) in LPS-stimulated RAW264.7 cells. Additionally, the MC fraction could suppress not only the LPS-induced nuclear translocation of cytosolic NF-kB, but also the LPS-induced activation of MAPKs, such as ERK, JNK, and p38MAPK. Further analysis of the MC fraction by HPLC identified kaempferol, biochanin A, and formononetin as the major phenolic components. Both kaempferol and biochanin A, but not formononetin, could exert anti-inflammatory effect at the same concentrations as those of the MC fraction. Consequently, these results indicate that kaempferol and biochanin A are among the most effective anti-inflammatory phenolic components in barnyard millet grains. This finding suggests that barnyard millet grains and the MC extract enriched in kaempferol and biochanin A could be beneficial functional food sources that have an anti-inflammatory effect.

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.

The Effect of Transplantation of Schwann Cell and SIS Sponge on the Injured Peripheral Nerve Regeneration (슈반세포와 SIS 스폰지의 이식이 손상된 말초 신경 재생에 미치는 영향)

  • Kim, Cho-Min;Kim, Soon-Hee;Kim, Su-Mi;Park, Sang-Wook;Lee, Il-Woo;Kim, Moon-Suk;Rhee, John-M.;Khang, Gil-Son;Lee, Hai-Bang
    • Polymer(Korea)
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    • v.32 no.1
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    • pp.49-55
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    • 2008
  • It is recognized that Schwann cells (SC) are essential for peripheral nerve development and regeneration. SIS (small intestinal submucosa) consists of some growth factors which can stimulate cell activity without immune rejection responges. SCs were harvested from the femurs and tibias of female Fischer rat and then suspended with $2{\times}10^6$ cell/sponge in SIS sponge. Fischer rat received an implant consisting of the SCs and the SIS sponge at the place of a 5 mm gap created by the sciatic nerve resection. Thin sections were stained with H &E staining and immunostaining of S-100, GFAP and NF after 1, 2, and 4 weeks. It was observed that the effects of the SIS sponge with SCs on neuroinduction(Group II, with scaffold & cell) are strong as much as uninjured model(Control I), and significantly stronger than SIS sponge model (Group 1, with scaffold only) and blank model (Control II). In conclusion, these results suggest that SIS sponge filled with SCs may have an important role for peripheral nerve regeneration of tissue engineering.

The Protective Effect of Water Extract of Phellodendri Cortex in Chronic Reflux Esophagitis-induced Rats (만성 역류성 식도염 동물 모델에 대한 황백(黃柏) 물 추출물의 식도 점막 보호 효과)

  • Lee, Se Hui;Lee, Jin A;Shin, Mi-rae;Lee, Ji Hye;Roh, Seong-soo
    • The Korea Journal of Herbology
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    • v.35 no.4
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    • pp.25-36
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    • 2020
  • Objective : Reflux esophagitis is a disease caused by the reflux of gastric acid and inflammation due to unstable gastroesophageal sphincter. The aim of the present study was to clarify the effect of Phellodendri Cortex (PC) on chronic reflux esophagitis (CRE) in rats. Methods : The anti-oxidant activity of PC was measured by total polyphenol, total flavonoid contents, 1, 1-diphenyl-2-picrylhydrazyl (DPPH), and 2, 2'-azinobis-3-ethyl-enzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity. A CRE was established surgically in SD rats. And then CRE rats were treated with water or PC 200 mg/kg body weight for 14 days. Besides, the anti-oxidant and inflammatory protein levels were evaluated using western blotting. Results : PC reduced esophagus tissues injury. The total polyphenol (36.05 ± 0.25 mg/g) and total flavonoid (72.90 ± 0.61 mg/g) of PC showed a high content. PC strongly reduced radical scavenging activities (DPPH IC50 43.58 ± 1.54 ㎍/㎖; ABTS IC50 36.75 ± 0.35 ㎍/㎖). Moreover, reactive oxygen species (ROS) and peroxynitrite (ONOO-) levels in serum, the protein expression of inducible nitric oxide synthases (iNOS) were significantly reduced. In addition, the protein expression of NADPH oxidases related to oxidative stress were significantly reduced in PC compared to CRE control. PC effectively reduced inflammatory factors including, TNF-α, and IL-6 via NF-κBp65 inactivation through the inhibition of p-IκBα and increased anti-oxidant enzyme such as HO-1, SOD, catalase, and GPx-1/2 via Nrf2 activation. Conclusions : Taken together, these results show that PC can alleviate the esophageal mucosal ulcer though the inhibition of NF-κB inflammatory and the enhancement of Nrf2 anti-oxidant pathway.

Anti-inflammatory effect of zaluzanin C on lipopolysaccharide-stimulated murine macrophages (지방질다당류로 자극한 마우스 대식세포에 있어서 zaluzanin C의 항염증 효과)

  • Kang, Ye Rim;Lee, Hee Won;Kim, Yoon Hee
    • Korean Journal of Food Science and Technology
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    • v.48 no.4
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    • pp.392-397
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    • 2016
  • Zaluzanin C is a sesquiterpene lactone isolated from Ainsliaea acerifolia, a Korean medicinal plant. In the present study, the anti-inflammatory effects of zaluzanin C were demonstrated in lipopolysaccharide (LPS)-stimulated murine macrophages (RAW264.7 cells). Zaluzanin C inhibited the release of nitric oxide (NO) by alleviating the protein expression of inducible NO synthase in LPS-treated RAW264.7 cells. Furthermore, it suppressed the release of interleukin-6 induced by LPS. Zaluzanin C was also found to block the translocation of the p65 subunit of nuclear factor-kB from the cytosol to the nucleus, which is one of the underlying mechanisms of the anti-inflammatory action of zaluzanin C. These data suggest the potential of zaluzanin C in the treatment of inflammatory diseases.