• 한국식품과학회지
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• 제52권3호
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• pp.249-254
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• 2020

우리는 한국생명공학연구원에서 제공한 소재를 탐색 후 ACE를 선별하였고 이 소재의 항염증 효능을 평가하였다. ACE는 세포독성이 없는 농도에서 LPS에 의한 iNOS의 발현과 NO의 생성을 유의적으로 억제하였다. ACE는 LPS에 의해 증가한 IKK, IκB, p65의 인산화와 IL-1β의 생성을 유의적으로 억제하였다. 이 논문은 ACE가 NO/iNOS 발현 및 NF-κB 신호 전달 경로의 억제를 통해 항염증 효능을 나타냄을 밝힌 최초의 논문으로서 의의를 가진다. 또한 이 결과를 바탕으로 ACE는 항염증 기능성식품 또는 의약품소재로써 활용가치가 높을 것으로 기대된다.

• Molecules and Cells
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• 제44권11호
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• pp.784-794
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• 2021

Leiomyosarcoma (LMS) is a mesenchymal malignancy with a complex karyotype. Despite accumulated evidence, the factors contributing to the development of LMS are unclear. Here, we investigated the role of tight-junction protein 1 (TJP1), a membrane-associated intercellular barrier protein during the development of LMS and the tumor microenvironment. We orthotopically transplanted SK-LMS-1 cells and their derivatives in terms of TJP1 expression by intramuscular injection, such as SK-LMS-1 Sh-Control cells and SK-LMS-1 Sh-TJP1. We observed robust tumor growth in mice transplanted with LMS cell lines expressing TJP1 while no tumor mass was found in mice transplanted with SK-LMS-1 Sh-TJP1 cells with silenced TJP1 expression. Tissues from mice were stained and further analyzed to clarify the effects of TJP1 expression on tumor development and the tumor microenvironment. To identify the TJP1-dependent factors important in the development of LMS, genes with altered expression were selected in SK-LMS-1 cells such as cyclinD1, CSF1 and so on. The top 10% of highly expressed genes in LMS tissues were obtained from public databases. Further analysis revealed two clusters related to cell proliferation and the tumor microenvironment. Furthermore, integrated analyses of the gene expression networks revealed correlations among TJP1, CSF1 and CTLA4 at the mRNA level, suggesting a possible role for TJP1 in the immune environment. Taken together, these results imply that TJP1 contributes to the development of sarcoma by proliferation through modulating cell-cell aggregation and communication through cytokines in the tumor microenvironment and might be a beneficial therapeutic target.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3909-3919
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• 2013

The aim of the present investigation was to evaluate the effect of A ferruginea extract on Dalton's lymphoma ascites (DLA) induced tumours in BALB/c mice. Experimental animals received A ferruginea extract (10 mg/kg.b.wt) intraperitoneally for 14 consecutive days after DLA tumor challenge. Treatment with extract significantly increased the life span, total white blood cell (WBC) count and haemoglobin (Hb) content and decreased the level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (${\gamma}$-GT) and nitric oxide (NO) in DLA bearing ascites tumor models. In addition, administration of extract significantly decreased the tumour volume and body weight in a DLA bearing solid tumor model. The levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF), as well as pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were elevated in solid tumour controls, but significantly reduced by A ferruginea administration. On the other hand, the extract stimulated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-${\gamma}$) in animals with DLA induced solid tumours. Increase in $CD4^+$ T-cell population suggested strong immunostimulant activity for this extract. GC/MS and LC/MS analysis showed quinone, quinoline, imidazolidine, pyrrolidine, cyclopentenone, thiazole, pyrazole, catechin and coumarin derivatives as major compounds present in the A ferruginea methanolic extract. Thus, the outcome of the present study suggests that A ferruginea extract has immunomodulatory and tumor inhibitory activities and has the potential to be developed as a natural anticancer agent.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1087-1095
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• 2003

Betulinic acid (BA), a pentacyclic triterpene isolated from Lycopus lucidus, has been reported to be a selective inducer of apoptosis in various human cancer and shown anti-inflammatory and immunomodulatory properties. We postulated that BA modulates the immunomodulatory properties at least two groups of protein mediators of inflammation, interlukin-1$\beta$ (IL-1$\beta$) and the tumor necrosis factor- $\alpha$ (TNF-$\alpha$) on the basis of the critical role of the monocytes and tissue macrophages in inflammatory and immune responses. TNF-$\alpha$ and IL-1$\beta$ were produced by BA in a dose dependent manner at concentration of 0.625 and 10 $\mu$g/mL. The production of NO associated with iNOS was inhibited when treated with LPS at the concentration of 2.5 to 20 $\mu$g/mL of BA whereas COX-2 expression was decreased at 2.5 to 20 $\mu$g/mL. These modulations of inflammatory mediators were examined in LPS-stimulated RAW 264.7 cells and peritoneal macrophages. The morphology of macrophage was also examined and enhanced surface CD 40 molecule was expressed when treated BA at 0.625∼5 $\mu$g/mL with or without LPS. Furthermore, BA (20 $\mu$g/mL) enhanced apoptosis by producing DNA ladder in the RAW 264.7 cells. Our results indicated that BA induced activation of macrophage and pro-inflammatory cytokines. This may provide a molecular basis for the ability of BA to mediate macrophage, suppress inflammation, and modulate the immune response.

• 한국식품저장유통학회지
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• 제21권5호
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• pp.740-746
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• 2014

적하수오 추출물의 추출용매별 항염증 작용을 알아보기 위해 LPS로 자극된 RAW 264.7 세포를 이용하여 실험을 진행 한 결과 열수 추출물 및 70% 에탄올 추출물 모두 $100{\mu}g/mL$에서 60%이상의 NO 생성 억제 율을 보이는 것을 확인 하였다. 또한 사이토 카인들에 대하여 적하수오 추출물은 TNF-${\alpha}$, IL-$1{\beta}$, IL-6, $PGE_2$ 생성량은 농도 의존적으로 감소하였고, 이는 적하수오 추출물이 염증성 사이토 카인의 발현을 억제 하여 염증 발생을 억제 할 수 있다고 할 수 있다. PMW는 $100{\mu}g/mL$의 농도에서 iNOS 단백질 발현량이 89%, COX-2는 54%의 효과를 나타내었으며, PME는 $100{\mu}g/mL$의 농도에서 iNOS 91%, COX-2는 57%의 단백질 발현 저해효과가 있음을 확인 할 결과로 보아 적하수오는 대식세포에서 NO, TNF-${\alpha}$, IL-$1{\beta}$, IL-6, PGE2 iNOS, COX-2 발현을 억제 하며, 특히 적하수오 70% 에탄올 추출물의 경우 저 농도에서부터 효과를 나타내어 우수한 항염증 소재임을 확인 할 수 있었다.

• 한국식품영양학회지
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• 제35권2호
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• pp.116-126
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• 2022

The purpose of this study was to analyze the anti-inflammatory effect of Chung-Dae Indigo Pulverata Levis, indigo naturalis) produced during indigo dyeing. As a result of in vitro cytotoxicity experiments using RAW 264.7 cell, Chung-Dae extract did not inhibit cell proliferation in Raw 264.7 cells in the range of 1~32 ㎍/mL. NO production was significantly reduced when Chung-Dae extracts were treated at concentrations of 2, 8, and 32 ㎍/mL (p<0.05). The pro-inflammatory cytokines TNF-α, IL-6, IL-1β and IFN-γ significantly decreased when the Chung-Dae extract was treated at concentrations of 2, 8, and 32 ㎍/mL compared to the LPS group, and similarly, the TNFα and IL-6 mRNA levels also decreased. Additionally, the mRNA level of COX-2 was also suppressed. At the protein expression level, the expression of TNF-α, IL-6, iNOS and COX-2 were observed with LPS and Chung-Dae extract significantly decreased compared to the group treated with only LPS (p<0.05). From the above results, it shows that Chung-Dae extract, a plant-derived compound, inhibits the inflammatory response induced by LPS in RAW 264.7 cells. and in particular, regulates the inflammatory response by inhibiting the expression of pro-inflammatory cytokines and inflammation-related enzymes.

• 한국식품영양학회지
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• 제37권2호
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• pp.110-122
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• 2024

This study investigated major constituents and anti-inflammatory effects of an ethanol extract of Platycodon grandiflorum leaves. Through HPLC analysis, chlorogenic acid and luteolin-7-O-glucoside were identified as predominant constituents in the ethanol extract. Their anti-inflammatory effects were evaluated using murine macrophage (RAW 264.7 cells) and human lung carcinoma cells (NCI-H292 & A549). The ethanol extract significantly (p<0.01) inhibited the production of nitrite, interleukin-6 (IL-6), and prostaglandin E2 (PGE2) induced by lipopolysaccharide (LPS) in RAW 264.7 cells. Furthermore, the ethanol extract suppressed the expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) proteins in RAW 264.7 cells stimulated with LPS. In NCI-H292 and A549 cells, treatment with the ethanol extract significantly (p<0.05) decreased levels of pro-inflammatory cytokines IL-6 and IL-8 induced by IL-1β. The phosphorylation of ERK rather than JNK in the mitogen-activated protein kinase signaling pathway was observed to be a more important mediator in the down-regulation of pro-inflammatory cytokines in NCI-H292 cells. These findings suggest that the ethanol extract of Platycodon grandiflorum leaves containing luteolin-7-O-glucoside exhibits promising anti-inflammatory properties.

• 한국식품영양과학회지
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• 제44권2호
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• pp.182-190
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• 2015

본 연구는 홍삼추출물(홍삼단)과 생약복합추출물(헤모힘)이 주요 기능성분은 다르지만 면역활성이라는 생리활성 측면에서 동일한 효과를 인정하고 있어서 이들의 병용 처리가 면역세포에 어떠한 영향을 미치는지에 대해 알아보기 위하여 수행되었다. 면역활성능에 관한 평가를 진행하기 위하여 마우스의 골수에서 분리한 미분화 골수세포를 선천면역에서 중요한 역할을 수행하는 대식세포 및 수지상세포로 분화시킨 후 홍삼추출물과 생약복합추출물을 병용 처리하였을 때 대식세포 및 수지상세포의 세포 증식능 및 사이토카인의 분비능이 증가되는 것으로 관찰되었다. 또한 활성화된 탐식(면역)세포의 세포 표면에서 발현되는 CD80과 CD86의 발현과 탐식(면역)세포의 항원제시에 밀접한 관련이 있는 주 조직적합성 복합체(MHC class II)의 발현이 홍삼추출물과 생약복합추출물의 병용 처리구에서 유의적으로 증가되는 것으로 관찰되었다. 또한 후천면역에서 중요한 역할을 수행하는 면역 T 세포가 다량으로 분포하는 비장 조직으로부터 비장세포를 분리하여 홍삼추출물과 생약복합추출물을 병용처리하였을 때 세포 증식능 및 면역활성을 유도하는 Th1 세포가 분비하는 사이토카인의 함량이 증가되는 것으로 나타났다. 이러한 결과로 미루어 볼 때 홍삼추출물과 생약복합 추출물의 병용 처리는 선천면역뿐만 아니라 후천면역에 관여하는 다양한 면역세포의 활성화에 직 간접적으로 다양한 상승작용을 미치는 것으로 사료된다.

• Parasites, Hosts and Diseases
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• 제55권6호
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• pp.587-599
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• 2017

The immune response against Trichinella spiralis at the intestinal level depends on the $CD4^+$ T cells, which can both suppress or promote the inflammatory response through the synthesis of diverse cytokines. During the intestinal phase, the immune response is mixed (Th1/Th2) with the initial predominance of the Th1 response and the subsequent domination of Th2 response, which favor the development of intestinal pathology. In this context, the glucocorticoids (GC) are the pharmacotherapy for the intestinal inflammatory response in trichinellosis. However, its therapeutic use is limited, since studies have shown that treatment with GC suppresses the host immune system, favoring T. spiralis infection. In the search for novel pharmacological strategies that inhibit the Th1 immune response (proinflammatory) and assist the host against T. spiralis infection, recent studies showed that resiniferatoxin (RTX) had anti-inflammatory activity, which decreased the serum levels of IL-12, $INF-{\gamma}$, $IL-1{\beta}$, $TNF-{\alpha}$, NO, and $PGE_2$, as well the number of eosinophils in the blood, associated with decreased intestinal pathology and muscle parasite burden. These researches demonstrate that RTX is capable to inhibit the production of Th1 cytokines, contributing to the defense against T. spiralis infection, which places it as a new potential drug modulator of the immune response.

• 생약학회지
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• 제39권2호
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• pp.110-117
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• 2008

In this study, we investigated the anti-inflammatory effects of salidroside (SAL) isolated from the MeOH extract of Acer tegmentosum Maxim heartwood in RAW 264.7 macrophage cells. SAL pretreatment significantly inhibited nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) productions in the lipopolysaccharide (LPS)-induced RAW 264.7 cells. Western blot and RT-PCR analyses revealed that SAL inhibited the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in a concentration-dependent manner. In addition, SAL reduced the release and the mRNA expressions of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and interleukin-6 (IL-6). Furthermore, nuclear factorkappa B ($NF{-\kappa}B$) luciferase reporter assay was performed to know the involvement of SAL in the production of pro-inflammatory cytokines, we confirmed that LPS-induced transcription activity of $NF{-\kappa}B$ was inhibited by SAL. Taken together, our data indicate that anti-inflammatory property of salidroside might be the result from the inhibition of iNOS, COX-2, $TNF-{\alpha}$ and IL-6 expressions via the down-regulation of $NF{-\kappa}B$ activity.