• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9185-9190
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• 2014

Cyclo-oxygenase-2(Cox-2), a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth. Therefore, a better understanding of the regulatory mechanisms of Cox-2 could lead to novel targeted cancer therapies. MicroRNAs are strongly implicated in colorectal cancer but their specific roles and functions have yet to be fully elucidated. MiR-1297 plays an important role in lung adenocarcinoma and laryngeal squamous cell carcinoma, but its significance in colorectal cancer (CRC) has yet to be reported. In our present study, we found miR-1297 to be down regulated in both CRC-derived cell lines and clinical CRC samples, when compared with normal tissues. Furthermore, miR-1297 could inhibit human colorectal cancer LOVO and HCT116 cell proliferation, migration, and invasion in vitro and tumorigenesis in vivo by targeting Cox-2. Moreover, miR-1297 directly binds to the 3'-UTR of Cox-2, and the expression level was drastically decreased in LOVO and HCT116 cells following overexpression of miR-1297. Additionally, Cox-2 expression levels are inversely correlated with miR-1297 expression in human colorectal cancer xenograft tissues. These results imply that miR-1297 has the potential to provide a new approach to colorectal cancer therapy by directly inhibiting Cox-2 expression.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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• pp.1-8
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• 2001

Increased expression of inducible cyclo-oxygenase (COX-2) is associated with a wide variety of tumours. In addition inhibitors of COX have shown a great deal of promise in vitro and in animal models as potential anti-tumour therapies. COX enzymes utilise the substrate arachidonic acid to produce prostaglandin (PO)H$_2$, the precursor to all the prostanoids.(omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.217.1-217.1
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• 2003

In previous study, we investigated the mechanism of suppression of inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) by ergolide, sesquiterpene lactone from Inula Britannica. In this study, the suppression of iNOS and COX-2 by ergolide might be attributed to selective inhibition of NF-$\_$K/B signaling pathways. Here, we investigated the suppressionmechanism of NF-$\_$K/B signaling pathways by ergolide in TPA-stimulated HeLa cells. (omitted)

• 동의생리병리학회지
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• 제16권5호
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• pp.1048-1054
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• 2002

Silsosangami(SSG) is a formula of oriental medicines as an effective biological response modifier for augmenting host homeostasis of body circulation. Also SSG has been known to have an anti-diabetic activity and anti-platelet aggregation activity. The present study was undertaken to examine the effects of a new SSG on murine macrophage and human neutrophil functions as well as on several enzymes relevant to the inflammatory process. The results of the present study indicate that SSG exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of PGE2 production, which could be due to a decreased expression of and COX-2.

• Journal of Korean Neurosurgical Society
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• 제48권1호
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• pp.1-7
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• 2010

Objective : Notochordal cells in the intervertebral disc interact with nucleus pulposus (NP) cells and support the maintenance of disc homeostasis by regulation of matrix production. However, the influence of notochordal cells has not been evaluated in the annulus fibrosus (AF), which is the primary pain generator in the disc. We hypothesized that the notochordal cell has the capacity to modulate inflammatory mediators secreted by AF cells secondary to stimulation. Methods : Notochordal and AF cells were isolated from adult New Zealand white rabbits. AF pellets were cultured with notochordal cell clusters or in notochordal cell-conditioned media (NCCM) for 24 or 48 hours with proinflammatory cytokines at varying concentrations. Gene expression in AF pellets were assayed for nitric oxide synthase (iNOS), cyclo-oxygenase (COX)-2, and interleukin (IL)-6 by real time reverse transcriptase polymerase chain reaction (RT-PCR). Results : AF pellet in NCCM significantly decreased the iNOS and COX-2 messenger ribonucleic acid (mRNA) levels compared to AF pellets alone and AF pellets with notochordal cells (p < 0.05). AF pellet resulted in dose-dependent iNOS and COX-2 expression in response to IL-$1{\beta}$, stimulation, demonstrating that 1 ng/ml for 24 hours yielded a maximal response. AF pellet in NCCM significantly decreased the expression of iNOS and COX-2 in response to 1ng/ml IL-$1{\beta}$, stimulation at 24 hours (p < 0.05). There was no difference in IL-6 expression compared to AF pellets alone or AF pellets with notochordal cell clusters. Conclusion : We conclude that soluble factors from notochordal cells mitigate the gene expression of inflammatory mediators in stimulated AF, as expected after annular injury, suggesting that notochordal cells could serve as a novel therapeutic approach in symptomatic disc development.

• 생명과학회지
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• 제24권4호
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• pp.370-376
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• 2014

본 연구에서는 벼메뚜기 에탄올 추출물의 항염증 효능을 분석하기 위해 LPS로 염증 유도된 RAW 264.7 세포를 이용하였다. OCE의 항염증 효능을 확인 하기 위해서, 염증 유도된 RAW 264.7 세포에 대해 OCE 농도 의존적으로 염증성 사이토카인인 TNF-${\alpha}$와 IL-6의 유전자발현 및 단백질 생성을 감소시킴을 real-time PCR과 ELISA로 확인하였다. 또한, NF-${\kappa}B$ p65의 핵으로 이동이 차단됨을 면역형광염색으로 확인하였으며, iNOS와 COX-2 단백질 발현을 감소시키는 것을 Western blot 분석으로 확인하였다. 이상의 연구결과를 통해 벼메뚜기는 염증에 의한 NF-${\kappa}B$ p65의 활성과 TNF-${\alpha}$와 IL-6의 생성과 iNOS 및 COX-2의 발현을 억제하는 항염증 효능을 갖고 있는 것을 확인하였다.

• Journal of Acupuncture Research
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• 제29권1호
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• pp.103-113
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• 2012

Objectives : The purpose of this study is to evaluate effect of suppressing the expression of cyclo-oxygenase-type-2 (COX-2) as a consequence of inhibition macrophage migration inhibitory factor (MIF) activation by $Sambucus$ $williamsii$ $Hance$ (SWH) pharmacopunctureon rheumatoid arthritis (RA). Methods : In vitro test, synoviocytes extracted from type II collagen-induced arthritis (CIA) mouse's knee joint were cultivated After that, each well of synoviocytes was mixed with the extract of SWH at the dosage of $0.4mg/m{\ell}$, $0.6mg/m{\ell}$, $0.8mg/m{\ell}$, and $1.0mg/m{\ell}$ respectively, and cultivated for 24 hours after the addition. Reverse transcriptase - polymerase chain reaction (RT-PCR) is used to investigate the expression of MIF, Tumor necrosis factor (TNF)-${\alpha}$, COX-2 mRNA. $In$ $vivo$ test, thirty DBA female mice were used, and each ten mice were allocated into three group; normal group, CIA-elicitated group, and group treated with SWH pharmacopuncture on it's the point of $ST_{35}$ after CIA elicitation. It is investigated that change of mice foot thickness, histologic change of sliced synovial joint of mouse, and extent change of MIF, TNF-${\alpha}$, COX-2 in synovial membrane. Results : $In$ $vitro$ test, the expressions of cytokine(MIF, TNF-${\alpha}$, COX-2) mRNAs related to RA were dose-dependent decreased. In the SWH pharmacopuncture group, foot thickness and histologic change of sliced synovial joint were decreased comparing with CIA-elicitated group's change. In the SWH pharmacopuncture group, the suppression of MIF, TNF-${\alpha}$, COX-2 in synovial membrane was clearly shown comparing with CIA-elicitated group's change. Conclusions : It might be suggested that SWH pharmacopuncture mitigate tissue damage originated from rheumatoid arthritis by suppressing the expression of COX-2 as a consequence of inhibition MIF activation.

• 한국자원식물학회지
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• 제26권5호
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• pp.533-538
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• 2013

본 연구센터에서는 백색과 황색의 기존 품종의 감자보다 anthocyanin함량이 높고 생리활성이 우수한 것으로 확인된 신품종인 컬러감자 '홍영'과 '자영'을 개발하였으며, 차후 컬러감자를 산업화 용도로 가공 시 전량 폐기되는 외피의 활용도를 높이기 위하여 다음과 같은 생리활성 연구를 실시하였다. 컬러감자외피의 추출물과 분획물을 이용하여 항염증 효과를 검토한 결과, 대식세포인 RAW264.7 cell에서 염증매개물질인 lipopoly sacchride(LPS)로 염증을 유발시켜 nitric oxide(NO), prostagland-in $E_2(PGE_2)$ inducible nitric oxide synthase(iNOS), 그리고 cyclo oxygenase-2(COX-2)같은 염증유발인자들의 억제효과를 확인하였다. 자색감자인 자영외피 Chloroform분획물의 염증유발인자 억제 시 $IC_{50}$ value를 측정하여 $25{\sim}50{\mu}g/ml$의 농도에서 유의성 있는 항염증 효과를 보였다. Nitric oxide 생성을 농도의존적으로 현저하게 저해하는 농도는 $36.15{\mu}g/ml$이며, 세포독성이 없는 최고 농도인 $100{\mu}g/ml$의 농도에서 LPS에 의해 유도된 $PGE_2$를 76.68%만큼 유의성 있는 저해 효과를 보였다. 그리고 iNOS와 COX-2단백질을 유의성 있게 저해하는 농도는 $50{\mu}g/ml$ 처리였으며, 특이적으로 iNOS는 $25{\mu}g/ml$을 처리하였을 때부터 유의성 있는 저해효과를 보였다. 따라서 본 연구 결과는 자영외피의 chloroform 분획물이 유의성 있는 항염증 효과를 나타내며, 이러한 효능은 예방의학적 기능성을 충분이 가지고 있기에 염증성질환의 예방을 위한 건강기능성식품의 개발가능성을 제시할 수 있을 것으로 사료된다.

• 한방재활의학과학회지
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• 제21권1호
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• pp.57-77
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• 2011

Objectives : This study was to investigate the suppression effects of Sopunghwalhyeol-tang(Shufenghuoxie-tang) on the monosodium iodoacetate-induced osteoarthritis in rats. Methods : Arthritis was induced by injection of monosodium iodoacetate(0.5 mg) into the both knee joints of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was taken distilled water for 20 days. Treated group was taken extracts of Sopunghwalhyeol-tang(Shufenghuoxie-tang) by oraly for same duration. Normal group(n=8) was injected with normal saline and was taken distilled water for 20 days. Macroscopic examination and histopathological study on articular cartilage of knee joint were operated at 20 days after injection. Proteoglycan(PG) content of articular cartilages of knee joint was represented by safranine O staining, was measured at 20 days after injection. Tumor necrosis $factor-{\alpha}(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta})$, in synovial fluid were measured with enzyme-linked immuno sorbent assay(ELISA) kit at 20 days after injection. Immunohistochemical staining of cyclo-oxygenase-2(COX-2), inducible nitric oxide synthase(iNOS) in knee joints were observed at 20 days after injection. Results : 1. Lymphocytes in peripheral blood the treated group was significantly decreased compared with the control group. 2. PG content in articular cartilage of the treated group was significantly increased compared with the control group. 3. Histopathologically, osteoarthritic scores of the treated group was significantly decreased compared with the control group. 4. $TNF-{\alpha}$ content in synovial fluid of the treated group was significantly decreased compared with the control group. 5. COX-2 revelation index in chondrocytes and synovial membrane of the treated group was significantly decreased compared with the control group. 6. Matrix metalloproteinase-3(MMP-3) revelation index in chondrocytes and synovial membrane of the treated group was significantly decreased compared with the control group. Conclusions : On the basis of these results, we concluded that Sopunghwalhyeol-tang(Shufenghuoxie-tang) has inhibiting effects on the $TNF-{\alpha}$, COX-2 and MMP-3 secretion of chondrocytes and synovial membrane in Monosodium Iodoacetate-induced osteoarthritis model of rats.

• 한국식품영양과학회지
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• 제42권3호
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• pp.369-377
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• 2013

고구마뿌리에 비하여 많은 양이 폐기되는 고구마 줄기와 잎의 이용을 활성화시키고 기능성식품 소재로의 가능성을 알아보기 위하여 잎이 달려 있는 보라색 고구마줄기를 재래시장에서 구입하여 고구마잎(SL), 고구마줄기(ST), 껍질 제거한 고구마줄기(PST)의 총 폴리페놀과 총 플라보노이드 함량을 측정하고, in vitro 시스템에서의 항산화효과, 항알레르기 및 항염증효과를 검색하고자 하였다. 고구마잎은 데치고, 고구마줄기는 생으로 동결건조한 후 에탄올 추출물을 얻어 실험하였다. 총 폴리페놀 함량은 SL(11.03 mg tannic acid/g)> ST(0.87 mg tannic acid/g)> PST(0.37 mg tannic acid/g)이었고, 총 플라보노이드 함량은 SL(9.01 mg rutin/g)> ST(0.50 mg rutin/g)> PST(0.25 mg rutin/g)이었다(p<0.001). DPPH 라디칼을 50% 제거시키는 에탄올 추출물의 농도($IC_{50}$)는 SL($43.6{\mu}g/mL$)< ST($308.4{\mu}g/mL$)$1,631.3{\mu}g/mL$)로 고구마잎이 가장 우수한 효과를 나타내었다. 양성대조시약으로 사용한 BHA의 $IC_{50}$값은 $8.30{\mu}g/mL$이었으며, 처리 농도 $1,000{\mu}g/mL$에서의 환원력은 SL($59.72{\mu}g$ ascorbic acid eq./mL)> ST($12.56{\mu}g$ ascorbic acid eq./mL)> PST($2.18{\mu}g$ ascorbic acid eq./mL)로 고구마잎이 가장 좋았다(p<0.001). 한편 염증반응에 관여하는 xanthine oxidase(XO) 활성저해율을 측정한 결과 처리 농도 $250{\mu}g/mL$에서 SL(13.06%)> ST(5.05%)> PST(0.0%)로 고구마잎이 줄기에 비하여 우수하였으며(p<0.01), 처리 농도 $50{\mu}g/mL$에서의 5-lipoxygenase(LOX) 활성저해율은 SL(91.16%)> ST(33.38%)> PST(14.93%)로(p<0.001) 고구마잎의 효과는 양성대조시약인 EGCG의 저해율(94.42%)과 비슷한 정도로 매우 우수하였다. 또한 $250{\mu}g/mL$ 농도로 처리 시 cyclooxygenase(COX)-2 활성저해율은 SL(55.34%)> ST(2.18%)> PST(0.0%)로 XO 활성저해율과 비슷한 패턴을 보였다(p<0.001). 측정변수들 간의 상관관계를 분석해 본 결과 총 폴리페놀 함량은 플라보노이드 함량($r^2$=0.9988, p<0.001), 환원력($r^2$=0.9982, p<0.001), XO 활성저해율($r^2$=0.8322, p<0.05), COX-2 활성저해율($r^2$=0.9950, p<0.001), 5-LOX 활성저해율과 양의 상관관계($r^2$=0.9823, p<0.001)를 나타내었으며, 플라보노이드 함량은 환원력($r^2$=0.9946, p<0.001), XO 활성저해율($r^2$=0.8392, p<0.05), 5-LOX 활성저해율($r^2$=0.9749, p<0.01), COX-2 활성저해율과 유의한 양의 상관관계($r^2$=0.9937, p<0.001)를 보였다. 또한, 환원력은 XO 활성 저해율($r^2$=0.8384, p<0.05), 5-LOX 활성저해율($r^2$=0.9883, p<0.001) 및 COX-2 활성저해율과 유의한 양의 상관관계($r^2$=0.9954, p<0.001)를 나타내었으며, XO 활성저해율은 5-LOX 활성저해율과 유의한 양의 상관관계를 보였으나($r^2$=0.8786, p<0.05) COX-2 활성저해율과는 상관성을 보이지 않았다. 5-LOX 활성저해율은 COX-2 활성저해율과 유의한 양의 상관관계($r^2$=0.9815, p<0.01)를 나타내었다. 이상의 결과들로부터 고구마잎은 폴리페놀 및 플라보노이드 함량이 매우 높았고 우수한 항산화효과를 보였으며, 알레르기 및 염증반응과 관련이 있는 효소인 XO, 5-LOX 및 COX-2의 활성도 모두 억제하는 효과도 우수하였지만 특히 5-LOX 활성 억제효과는 EGCG와 비슷한 정도로 매우 우수하였다. 따라서 건강을 위하여 고구마잎의 섭취를 증대시킬 수 있는 다양한 방안을 강구할 필요가 있으며, 고구마 줄기를 섭취할 경우에는 가능한 껍질을 모두 섭취하는 것이 좋겠다.