• Journal of Acupuncture Research
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• 제35권3호
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• pp.115-119
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• 2018

Background: The objective of this study was to determine the effects of Daegangwhal-Tang (DGHT) hot aqueous extract on production of inflammatory mediators and antioxidants in RAW 264.7 macrophage. Methods: DGHT was extracted with water, filtered, concentrated and freeze-dried to perform. Cytotoxicity of DGHT extract was performed by MTT assay. Activated macrophages were treated with varying concentrations of DGHT extract (10, 50, 100 and $200{\mu}g/mL$), and nitric oxide (NO) and prostaglandin E2 ($PGE_2$) concentrations were measured to detect anti-oxidative effects. Interleukin-6 (IL-6), interleukin-1 beta ($IL-1{\beta}$) and tumor necrosis factor-alpha($TNF-{\alpha}$) concentrations were also measured to detect inflammatory responses to DGHT Results: Cytotoxicity of DGHT extract at concentrations of 10, 50, 100 and $200{\mu}g/mL$ were not observed. NO production was significantly decreased in the DGHT hot aqueous extract $200{\mu}g/mL$ concentration group. $PGE_2$, IL-6, $IL-1{\beta}$ and $TNF-{\alpha}$ production was significantly decreased in the DGHT hot aqueous extract 100 and $200{\mu}g/mL$ concentration groups. DGHT hot aqueous extract appeared to have DPPH free radical scavenging capability at all of concentrations, but did not exceed 50%. Conclusion: These results suggest that DGHT hot aqueous extract has concentration-dependent anti-inflammatory and anti-oxidative effect.

• Biomolecules & Therapeutics
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• 제24권2호
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• pp.184-190
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• 2016

Rosa rugosa Thunb, a deciduous shrub of the genus Rosa, has been widely used to treat stomach aches, diarrhoea, pain, and chronic inflammatory disease in eastern Asia. In recent years, our research team has extensively studied the Rosa rugosa flower extract, and specifically undertook pharmacological experiments which have optimized the extraction process. Our methods have yielded a standard extract enriched in phenolic compounds, named PRE. Herein, we expand our efforts and evaluated the anti-inflammatory activity of PRE on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. PRE significantly inhibited production of nitric oxide (NO), prostaglandin $E_2(PGE_2)$, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and interleukin $1{\beta}$ (IL-$1{\beta}$), as well as expression of their synthesizing enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX-2). Furthermore, PRE inhibited activity of mitogen-activated protein kinases (MAPK) as well as nuclear factor-kappa B (NF-${\kappa}B$) signaling pathway. Our findings are the first to explain the anti-inflammatory mechanism by PRE in LPS-stimulated macrophages. Given these results, we propose that PRE has therapeutic potential in the prevention of inflammatory disorders.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4403-4408
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• 2013

Background: Chronic inflammation is considered as an important factor in the pathogenesis of lung cancer. The presence of inflammatory cells and higher levels of pro-inflammatory cytokines in the tumor microenvironment and their surrounding tissues is gaining much importance in research. Materials and Methods: One hundred ninety NSCLC cases and 200 age, smoking and sex matched controls were evaluated for association of IL-8 -251 (rs4073) and IL-8 -845 (rs2227532) in our population. Restriction fragment length polymorphism (RFLP) was used followed by direct sequencing for the detection of SNPs. Results: The IL-8 -845 polymorphism was not found in our population. No significant association was observed between the IL-8 -251 AT genotypes and IL-8 -25 AA genotypes and NSCLC (p=0.05) in our population. The IL-8 -251 A allele was also non-significant (p=0.05) in NSCLC patients. Conclusions: In conclusion, this report reveals lack of association between IL-8 - 251 A/T polymorphism and NSCLC in our Kashmir Valley population.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3605-3610
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• 2016

Background: Histone acetylation in chromatin structures plays a key role in regulation of gene transcription and is strictly controlled by histone acetyltransferase (HAT) and deacetylase (HDAC) activities. HDAC deregulation has been reported in several cancers. Materials and Methods: The expression of 10 HDACs (including HDAC class I and II) was studied by quantitative reverse transcription-PCR (qRT-PCR) in a cohort of mesenchymal stem cells (MM-MSCs) from 10 multiple myeloma patients with a median age 60y. The results were compared with those obtained for normal donors. Then, a coculture system was performed between MM-MSCs and u266 cell line, in the presence or absence of sodium butyrate (NaBT), to understand the effects of HDAC inhibitors (HDACi) in MM-MSCs on multiple myeloma cases. Also, the interleukin-6 (IL-6) and vascular endothelial growth factor (VEGFA) gene expression level and apoptotic effects were investigated in MM-MSCs patients and control group following NaBT treatment. Results: The results indicated that upregulated (HDACs) and downregulated (IL6 and VEGFA) genes were differentially expressed in the MM-MSCs derived from patients with multiple myeloma and ND-MSCs from normal donors. Comparison of the MM-MSCs and ND-MSCs also showed distinct HDACs expression patterns. For the first time to our knowledge, a significant increase of apoptosis was observed in coculture with MM-MSCs treated with NaBT. Conclusions: The obtained findings elucidate a complex set of actions in MSCs in response to HDAC inhibitors, which may be responsible for anticancer effects. Also, the data support the idea that MSCs are new therapeutic targets as a potential effective strategy for MM.

• BMB Reports
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• 제45권7호
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• pp.414-418
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• 2012

Triglycerides (TG) are implicated in the development of atherosclerosis through formation of foam cells and induction of macrophage cell death. In this study, we report that addition of exogenous TG induced cell death in phorbol 12-myristate 13-acetate-differentiated THP-1 human macrophages. TG treatment induced a dramatic decrease in interleukin-$1{\beta}$ (IL-$1{\beta}$) mRNA expression in a dose- and time-dependent manner. The expression of granulocyte macrophage colony-stimulating factor and platelet endothelial cell adhesion molecule remained unchanged. To identify signaling pathways involved in TG-induced downregulation of IL-$1{\beta}$, we added p38 MAPK, protein kinase C (PKC) or c-Raf1 specific inhibitors. We found that inhibition of p38 MAPK alleviated the TG-induced downregulation of IL-$1{\beta}$, whereas inhibition of PKC and c-Raf1 had no effect. This is the first report showing decreased IL-$1{\beta}$ expression during TG-induced cell death in a human macrophage line. Our results suggest that downregulation of IL-$1{\beta}$ expression by TG-treated macrophages may play a role during atherogenesis.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.363-372
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• 2020

Gardenia jasminoides (GJ) is a widely used herbal medicine with anti-inflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJ_EtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJ_EtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJ_HEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJ_HEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited I_ORAI1 and interleukin-2 production in CD3/CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4⁺ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

• 동의생리병리학회지
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• 제25권3호
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• pp.503-509
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• 2011

Jakyaktang(芍藥湯; JYT) exhibits potent anti-inflammatory activity in widely intestinal disease, but its mechanism was undisclosed. To elucidate the molecular mechanisms of JYT on pharmacological and biochemical actions in inflammation, we examined the effect of JYT on pro-inflammatory mediators in phorbol 12-myristate 13-acetate (PMA) plus A23187-induced mast cell and lipopolysaccharide (LPS)-stimulated macrophages. The investigation focused on whether JYT inhibited pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in PMA plus A23187- induced HMC-1 cells and inflammatory madiators such as nitric oxide (NO), TNF-${\alpha}$, IL-6, iNOS, COX-2 in LPS-stimulated RAW 264.7 cells. We found that JYT inhibited LPS-induced NO, TNF-${\alpha}$ and IL-6 productions as well as the expressions of iNOS and COX-2. These results suggest that JYT has inhibitory effects on mast cell-mediated and macropage-mediated inflammation.

• 셀메드
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• 제4권4호
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• pp.28.1-28.27
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• 2014

Linderae Radix, the dry roots of Lindera aggregata (Sims) Kosterm, has long been used as traditional Chinese medicine for treatment of inflammatory diseases. The total alkaloids are believed to be the active components responsible for anti-inflammation of Linderae Radix. Here, the total alkaloids of Linderae Radix were extracted and isolated, including 12 isoquinoline alkaloids and 1 furan sesquiterpene. Within the alkaloids, norisoboldine, boldine, linderaline, isoboldine, reticuline, N-methyllaurotetanine, norjuziphine were found to be the major ingredients. In lipopolysaccharide-treated macrophage RAW 264.7 cells, application of Linderae Radix extract, or total alkaloids, suppressed the transcription of proinflammatory cytokines, interleukin-$1{\beta}$ and interleukin-6. Out of the 12 alkaloids, norisoboldine, boldine, and isoboldine were tested in lipopolysaccharide-treated macrophages, and norisoboldine was the strongest alkaloid in suppressing the cytokine expressions. The current studies suggested that the identification of alkaloids from Linderae Radix could provide a plausible explanation for herbal therapeutic functions.

• 한국식품영양과학회지
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• 제40권3호
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• pp.372-378
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• 2011

본 실험에서는 군소로부터 다당류를 추출 정제한 다당 분획물을 혈액 림프구와 대식 세포주를 사용하여 면역 조절효과를 실험해 보았다. 군소부터 추출 분획한 다당류는 48시간 동안 처리 시 Jurkat cell의 증식률을 40% 이상 증가시켰으며, 혈액암 세포종인 Jiyoye cell에 대하여는 그 성장률이 농도에 따라 감소하였다. 그렇지만 Jurkat cell에 24시간과 48시간 동안 군소 다당 분획물을 처리하였을 때 IL-2와 IFN-$\gamma$ 생성량의 유의적인 증가는 확인할 수 없었다. 그러나 RAW264.7 cell line에 대하여는 IL-12의 경우는 47% 이상 증가하여, 군소 다당 분획물의 면역 조절 효과의 가능성을 보여주었다.

• KSBB Journal
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• 제5권2호
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• pp.113-118
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• 1990

생체내 중요한 면역조절물질의 하나인 IL-l은 주로 Macrophage로부터 분비되어 각종 면역반응에 관여하는 것으로 알려져 있는데 이러한 Macrophage에 의한 IL-I 생성에 미치는 Histamine의 효과를 검토하고자 Mac-rophage-like cell line인 $P388D^1$세포에 의한 IL-1생성에 미치는 Histamine의 첨가효과는 $10^-^8M~10^-^3M$에 이르기까지 전 범위에서 농도의존적으로 IL,-1생성을 촉진시켰으며 첨가후 배양시간에 있어서는 24~36시간이 가장 크게 상승되었다. Histamine에 의한 Macropahge로 부터의 IL-1생성은 EGTA 및 $Co^2^+$의 첨가로 인하여 농도의존적으로 저하되었으며 이 결과는 Histamine의 IL-1 생성촉진작용이 세포내로의 $Ca^2^+uptake가 signal 역할을 하고 있음을 시사한다. $P388D_1$세포로의 $Ca^2^+$uptake양을 동정한 결과는 Histamine의 $10^-^7M$에서 $10^-^3M$까지 농도의존적으로 $Ca^2^+3M$유입이 촉진되는 결과를 나타내었다.