• IMMUNE NETWORK
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• 제13권6호
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• pp.283-288
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• 2013

The pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ (TNF${\alpha}$) and interleukin (IL)-$1{\beta}$ are crucial mediators involved in chronic inflammatory diseases. Inflammatory signal pathways regulate inflammatory cytokine expression-mediated by p38 mitogen activated protein kinase (p38MAPK). Therefore, considerable attention has been given to p38MAPK as a target molecule for the development of a novel anti-inflammatory therapeutics. BIRB 796, one of p38MAPK inhibitor, is a candidate of therapeutic drug for chronic inflammatory diseases. In this study, we investigated the effect of BIRB 796 on inflammatory cytokine productions by lipopolysaccharide (LPS) in different immune cell types. BIRB 796 reduced LPS-mediated IL-8 production in THP-1 cells but not in Raw 264.7 cells. Further analysis of signal molecules by western blot revealed that BIRB 796 sufficiently suppressed LPS-mediated phosphorylation of p38MAPK in both cell types whereas it failed to block inhibitor of kappa B (I-${\kappa}B$) degradation in Raw 264.7 cells. Taken together, these results suggest that the anti-inflammatory function of BIRB 796 depends on cell types.

• Journal of Periodontal and Implant Science
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• 제38권3호
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• pp.543-550
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• 2008

Purpose: The purpose of this study was to investigate induction of cytokine expression in human gingival fibroblasts (HGFs) by whole cell and the components of T. forsythia. Material and Methods: After HGFs were treated with lipopolysaccharide (LPS), membrane protein isolated from T. forsythia or culture media of T. forsythia, the induction of interleukin (IL)-1, IL-6 and IL-8 was examined with real-time PCR and ELISA. Their induction ability of cytokines was compared with whole bacteria. Result: The expression of IL-6 and IL-8 was significantly induced in HGFs by whole bacteria and membrane protein. The expression of IL-$1{\beta}$ was induced by membrane protein of T. forsythia, not by whole bacteria. LPS and condition media of T. forsythia slightly activated HGFs. Conclusion: The membrane protein of T. forsythia could be one of virulence factors.

• The Korean Journal of Physiology and Pharmacology
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• 제10권2호
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• pp.85-94
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• 2006

A splanchic artery occlusion for 90 min followed by reperfusion of the mesenteric circulation resulted in a severe form of circulatory shock, characterized by endothelial dysfunction, severe hypotension, marked intestinal tissue injury, and a high mortality rate. The effect of defibrotide, a complex of single-stranded polydeoxyribonucleotides having antithrombotic effect, was investigated in a model of splanchnic artery occlusion (SAO) shock in urethane anesthetized rats. Occlusion of the superior mesenteric artery for 90 min produced a severe shock state, resulting in a fatal outcome within 120 min of reperfusion in many rats. Defibrotide (10 mg/kg body weight) 10 min prior to reperfusion significantly improved mean arterial blood pressure in comparison to vehicle treated rats (p＜0.05). Defibrotide treatment also significantly attenuated in the increase of plasma amino nitrogen concentration, intestinal myeloperoxidase activity, intestinal lipid peroxidation, infiltration of neutrophils in intestine and thrombin induced adherence of neutrophils to superior mesentric artery segments. Superoxide anion and hydrogen peroxide production in $1{\mu}M$ formylmethionylleucylphenylalanine (fMLP)-activated PMNs was inhibited by defibrotide in a dose-dependent fashion. Defibrotide effectively scavenged hydrogen peroxide, but not hydroxyl radical. Treatment of SAO rats with defibrotide inhibited tumor necrosis factor-${\alpha}$, and interleukin-1${\beta}$ productions in blood in comparison with untreated rats. These results suggest that defibrotide partly provides beneficial effects by preserving endothelial function, attenuating neutrophil accumulation, and antioxidant in the ischemic reperfused splanchnic circulation

• 동의생리병리학회지
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• 제20권4호
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• pp.853-860
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• 2006

This study was performed to investigate genes which are differently expressed in human blood by administrating of OLT-2. OLT-2 was medical precipitation composed of three medicinal herbs, Ginseng Radix, Astragali Radix, Glycyrrhizae Radix, and anti-leukemia effect of it was evaluated from Byung Hun Jeon of Wonkwang University this study was approved by Institutional Review Board of Korea Institute of Oriental Medicine (Taejeon, Korea) and four male subjects participated in this study. Gene expressions were evaluated by cDNA chip, in which 24,000 genes were spotted. Hierarchical cluster and biological process against the genes, which expression changes were more than 1.6 fold, were constructed by cluster 3.0 providing Stanford University and EASE(http://apps1 .maid.nih.gov/DAVID). Five groups were clustered according to their expression patterns. Group A contained gene decreased by OLT-2 and increased genes by OLT-2 were involved in Group B, C, D. In biological process, expression of genes involved in cytokine or cell calcium signaling, such as interleukin 18 and G-protein beta 4 were increased, but protein tyrosine phosphatase receptor type c, which function is cell adhesion between antigen-presenting cell and T or B-cell, was decreased by OLT-2. This study provides the most comprehensive available survey of gene expression changes in response to anti-leukemia effect of OLT-2 in human blood.

• Animal Bioscience
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• 제34권7호
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• pp.1221-1234
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• 2021

Objective: Weaning is an important stage in the life of young mammals, which is associated with intestinal inflammation, gut microbiota disorders, and even death. β-Carotene displays anti-inflammatory and antioxidant activities, which can prevent the development of inflammatory diseases. However, whether β-carotene can affect intestinal microbiota remains unclear. Methods: Twenty-four piglets were distributed into four groups: the normal suckling group (Con), the weaning group (WG), the weaning+β-carotene (40 mg/kg) group (LCBC), and the weaning+β-carotene (80 mg/kg) group (HCBC). The serum, jejunum, colon, and faeces were collected separately from each group. The effects of β-carotene on the phenotype, overall structure, and composition of gut microbiota were assessed in weaning piglets. Results: The results showed that β-carotene improved the growth performance, intestinal morphology and relieved inflammation. Furthermore, β-carotene significantly decreased the species from phyla Bacteroidetes and the genus Prevotella, and Blautia, and increased the species from the phyla Firmicutes and the genera p-75-a5, and Parabacteroides compared to the WG group. Spearman's correlation analysis showed that Prevotella and Blautia were positively correlated, and Parabacteroides and Synergistes were negatively correlated with the levels of interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α), while p-75-a5 showed negative correlation with IL-6 in serum samples from piglets. Conclusion: These findings indicate that β-carotene could alleviate weaning-induced intestinal inflammation by modulating gut microbiota in piglets. Prevotella may be a potential target of β-carotene in alleviating the weaning-induced intestinal inflammation in piglets.

• 대한약침학회지
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• 제20권2호
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• pp.93-99
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• 2017

Objectives: Selaginella bryopteris L. (family: Selaginaceae), is often used in traditional Indian systems of medicine for the prevention and cure of several disorders and for the treatment of patient with spermatorrhoea, venereal disease, constipation, colitis, urinary tract infections, fever, epilepsy, leucorrhoea, beri-beri and cancer. It is also used as a strength tonic. This study aimed to evaluate the mechanisms underlying the anti-inflammatory effects of topically administered aqueous, polar and non-polar methanolic fractions ($10mg/20{\mu}L$) of Selaginella bryopteris. Methods: An acute oral toxicity study of Selaginella bryopteris at doses from 250 to 2,000 mg/kg body weight (bw) was performed. Aqueous, polar and non-polar methanolic extracts ($10mg/20{\mu}L$) applied topically for 5 days were evaluated for their anti-inflammatory effects against 12-tetra-O-decanoyl phorbol acetate (TPA)- induced inflammation by using the redness in the ear, the ear's weight (edema), oxidative stress parameters, such as lipid-peroxide (LPO) and nitric oxide (NO), and the pro-inflammatory cytokines involved in inflammation, such as tumour necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$ and IL-6. Indomethacine ($0.5mg/20{\mu}L$) was used for the positive control. Results: Selaginella bryopteris produced no mortalities when administered orally at doses from 250 to 2,000 mg/kg bw. Topical treatment with the non-polar methanolic fraction ($10mg/20{\mu}L$) significantly suppressed redness ($2.4{\pm}0.5$) and edema ($30.4{\pm}1$) and effectively reduced the LPO level ($32.3{\pm}3.3$). The NO level was ($8.07{\pm}0.55$), and the $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 levels were decreased to $69.6{\pm}15.5$, $7.7{\pm}4.8$ and $82.6{\pm}5.9$, respectively. Conclusion: This study demonstrated for the first time the mechanisms underlying the anti-inflammatory effect of medicinal plants like Selaginella bryopteris and quantified the pharmacological interactions between them. The present study showed this herbal product to be a promising anti-inflammatory phytomedicine for the treatment of patients with inflammatory skin diseases.

• Nutrition Research and Practice
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• 제10권2호
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• pp.131-138
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• 2016

BACKGROUND/OBJECTIVES: Citrus and its peels have been used in Asian folk medicine due to abundant flavonoids and usage of citrus peels, which are byproducts from juice and/or jam processing, may be a good strategy. Therefore, the aim of this study was to examine antioxidant and anti-inflammatory effects of bioconversion of Jeju Hallabong tangor (Citrus kiyomi ${\times}$ ponkan; CKP) peels with cytolase (CKP-C) in RAW 264.7 cells. MATERIALS/METHODS: Glycosides of CKP were converted into aglycosides with cytolase treatment. RAW 264.7 cells were pre-treated with 0, 100, or $200{\mu}g/ml$ of citrus peel extracts for 4 h, followed by stimulation with $1{\mu}g/ml$ lipopolysaccharide (LPS) for 8 h. Cell viability, DPPH radical scavenging activity, nitric oxide (NO), and prostagladin $E_2$ ($PGE_2$) production were examined. Real time-PCR and western immunoblotting assay were performed for detection of mRNA and/or protein expression of pro-inflammatory mediators and cytokines, respectively. RESULTS: HPLC analysis showed that treatment of CKP with cytolase resulted in decreased flavanone rutinoside forms (narirutin and hesperidin) and increased flavanone aglycoside forms (naringenin and hesperetin). DPPH scavenging activities were observed in a dose-dependent manner for all of the citrus peel extracts and CKP-C was more potent than intact CKP. All of the citrus peel extracts decreased NO production by inducible nitric oxide synthase (iNOS) activity and $PGE_2$ production by COX-2. Higher dose of CKP and all CKP-C groups significantly decreased mRNA and protein expression of LPS-stimulated iNOS. Only $200{\mu}g/ml$ of CKP-C markedly decreased mRNA and protein expression of cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells. Both 100 and $200{\mu}g/ml$ of CKP-C notably inhibited mRNA levels of $interleukin-1{\beta}$ ($IL-1{\beta}$) and IL-6, whereas $200{\mu}g/ml$ CKP-C significantly inhibited mRNA levels of $TNF-{\alpha}$. CONCLUSIONS: This result suggests that bioconversion of citrus peels with cytolase may enrich aglycoside flavanones of citrus peels and provide more potent functional food materials for prevention of chronic diseases attributable to oxidation and inflammation by increasing radical scavenging activity and suppressing pro-inflammatory mediators and cytokines.

• 한국미생물·생명공학회지
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• 제44권4호
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• pp.442-451
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• 2016

본 연구에서는 미야베 에탄올 추출물의 항염증 활성을 확인하기 위해 LPS로 활성화된 RAW 264.7 세포와 croton-oil로 유도된 귀부종 동물 모델을 이용하였다. 그 결과, SMYEE 50 및 $100{\mu}g/ml$ 농도처리 시, LPS로 유도된 염증반응에서 $NF-{\kappa}B$ 활성 억제와 더불어 MAPKs의 인산화를 효과적으로 억제함을 보였다. LPS에 의해 증가된 NO와 전염증성 사이토카인의 분비량도 농도 의존적으로 감소하였다. 또한 SMYEE는 croton oil로 부종을 유발한 마우스모델에서 귀부종 억제효과를 나타내었고, 조직의 진피 두께 및 mast cell의 수가 현저히 감소하였음을 확인하였다. 이를 통해 SMYEE는 염증 반응의 전사인자인 $NF-{\kappa}B$ 및 MAPKs의 활성을 조절함으로써 iNOS와 COX-2의 발현 및 전염증성 매개인자인 NO, IL-6, $TNF-{\alpha}$ 및 $IL-1{\beta}$의 분비를 억제하여 항염증 활성을 가지는 것을 확인하였다. 현재까지 미야베 모자반내의 항염증 효능 물질에 관한 연구는 보고되지 않고 있으며 향후 실험을 통해 미야베 모자반 에탄올 추출물로부터 항염증 효과를 가지는 유효성분을 밝히기 위한 분리 연구를 진행할 예정이다.

• 혜화의학회지
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• 제18권1호
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• pp.29-41
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• 2009

Wished to examine closely effect that SoPungDoJeokTang-KaMi (SPDJTK) medicines used to atopy dermatitis disease patient get in atopy eruption control experimentally. SPDJTK medicines controlled $CD4^+/IFN-\gamma$, and $CD4^+/CD25^+/foxp3^+$ revelation that an experiment that motive allergy immune reponse because an in vitro experiment stimulates T cells of a NC/Nga mouse same time by anti-CD40/rmIL-4, and interleukin-$1{\beta}$, IL-6, TNF-$\alpha$, and TGF-$\beta$ mRNA outturn that bear in T and B cells decreased remarkably by SPDJTK medicines. Intracellular staining of splenocytes anti-CD40/rmIL-4 plus rmIL-4 stimulated as described in a, assessed after 24 h, SPDJTK exerts a mainly immunosuppressive effect that acts at least partially through suppression of the transcription factor GATA3 expression in $CD4^+$ T cells. Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen specially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were clinically and histologically very similar to human AD, mite antigen-induced dermatitis on the face, neck, ears and dorsal skin of inbred NC/Nga mice. Result that Th1 cell and Th2 cell observe to be shifted by cytokine expression with $CD4^+/CD25^+/foxp3^+$ Treg cells induction by SPDJTK medicines could know that SPDJTK medicines can use usefully in allergy autoimmnune diease.

• 한국식품영양과학회지
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• 제46권11호
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• pp.1271-1277
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• 2017

가미십전대보탕(이하 KSD로 표기) 추출물은 생약 성분으로 인체 및 동물에 투여 시 세포 독성 및 장기에 중금속 등에 의한 독성 물질이 발생할 수 있어 안전성이 매우 중요하다. 따라서 본 연구에서는 KSD의 안전성 확보를 위해 중금속 검사, 간과 신장 기능 지표 검사 및 RAW 264.7 세포 생존 시험을 거친 후 RAW 264.7 세포를 이용하여 KSD 추출물의 항산화 및 항염증 효과를 알아보았다. KSD 추출물에서 중금속은 발견되지 않거나 기준치 미만으로 검출되었다. 간기능지표인 AST, ALT는 정상군에 비해 낮게 나타났으며 신기능 지표인 Cr, BUN도 정상군과 같거나 낮아 인체에 안전함을 확인하였다. RAW 264.7 세포 독성은 대조군 대비 농도별 생존율에 차이가 없었다. KSD 추출물의 항산화 효능 측정 결과 DPPH 라디칼 소거능과 ABTS 라디칼 소거능은 $10{\mu}g/mL$ 이상의 농도에서 의존적으로 활성이 증가하였다. 항염증 효과 측정 결과 NO 생성량은 대조군에 비해 10, $100{\mu}g/mL$에서 유의성 있는 감소를 보였으며, $IL-1{\beta}$와 IL-6는 농도 의존적으로 발현량이 감소하였고, $TNF-{\alpha}$는 유의적 차이점을 발견할 수 없었다. 이상의 결과를 보아 KSD는 골절 치료를 위한 생약으로 안전성 및 항산화 및 염증 감소에 효과가 있을 것으로 생각된다.