• Archives of Pharmacal Research
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• 제26권5호
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• pp.383-388
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• 2003

Bee venom is used as a traditional medicine for treatment of arthritis. The anti-inflammatory activity of the n-hexane, ethyl acetate, and aqueous partitions from bee venom (Apis mellifera) was studied using cyclooxygenase (COX) activity and pro-inflammatory cytokines (TNF-$\alpha and IL-1\beta$) production, in vitro. COX-2 is involved in the production of prostaglandins that mediate pain and support the inflammatory process. The aqueous partition of bee venom showed strong dose-dependent inhibitory effects on COX-2 activity ($IC_{50} = 13.1 \mu$ g/mL), but did not inhibit COX-1 activity. The aqueous partition was subfractionated into three parts by molecular weight differences, namely, B-F1 (above 20 KDa), B-F2 (between 10 KDa and 20 KDa) and BF-3 (below 10 KDa). B-F2 and B-F3 strongly inhibited COX-2 activity and COX-2 mRNA expression in a dose-dependent manner, without revealing cytotoxic effects. TNF-$\alpha and IL-1\beta$ are potent pro-inflammatory cytokines and are early indicators of the inflammatory process. We also investigated the effects of three subfractions on TNF-$\alpha and IL-1\beta$ production using ELISA method. All three subfractions, B-F1, B-F2 and B-F3, inhibited TNF-$\alpha and IL-1\beta$production. These results suggest the pharmacological activities of bee venom on anti-inflammatory process include the inhibition of COX-2 expression and the blocking of pro-inflammatory cytokines (TNF-$\alpha and IL-1\beta$) production.

• 한방안이비인후피부과학회지
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• 제18권3호
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• pp.1-17
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• 2005

In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis of lung disease. This Experiment was conducted to investigate the effects of Sochungyong-tang on gene expressions in Mouse Alveolar Macrophage. Fer this purpose, we observed the cytokines ($IL-1{\beta}$, IL-6, IL-10, iNOS, $MIP-1{\alpha},\;MIP-1{\beta},\;MIP-1{\gamma},\;TGF-{\beta},\;TNF-{\alpha}$). We picked the alveolar macrophage out of mice and cultured it. We analyzed the cytokine gene expression by reverse transcription-PCR. The results obtained were as follows : 1 . Sochungyong-tang showed inhibitory effects on $IL-1{\beta}$ in time and concentration. 2. Sochungyong-tang showed inhibitory effects on IL-6 in time and concentration. 3. Sochungyong-tang showed inhibitory effects on IL-10 in concentration. 4. Sochungyong-tang showed inhibitory effects on iNOS. 5. Sochungyong-tang showed inhibitory effects on $TGF-{\beta}$ in time and concentration. 6. Sochungyong-tang showed on inhibitory effects on $MIP-1{\alpha},\;MIP-1{\beta},\;MIP-1{\gamma}$, $TCF-{\beta}$, $TNF-{\alpha}$. According to above results, it is supposed that Sochungyong-tang has the inhibitory effects on cytokine gene expression in mouse alveolar macrophage and can be usefully applied for curing inflammatory process of lung disease. Advanced studies are required to investigate the cure mechanism of Sochungyong-tang in the future.

• 대한한방부인과학회지
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• 제15권4호
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• pp.45-60
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• 2002

생쥐의 calvarial osteoblast세포를 분리배양하여 gelatinase생성여부를 골흡수과정에서의 역할을 규명하기 위하여 SDS-PAGE-zymography분석을 한 결과 progelatinase-A를 항속적으로 합성하고 있음을 확인하였다. 생쥐의 osteoblasts를 골재흡수 약물인 PTH, $1,25(OH)_2D_3$, 단핵구배양액 (MCM) 그리고 IL-1으로 자극시키면 gelatinase생산을 촉진하여 콜라겐분해가 증가되었으나, indomethacin과 dexamethasone은 생쥐의 osteoblastic세포의 collagenolysis를 저해하였다. 한편, 골재흡수에 IL-1을 생쥐태아 유래의 장골조직배양 (fetal mouse long bone organ culture)에 처리하자 IL-1 은 골재흡수를 촉진하였다. 더우기, $IL-1{\alpha}$의 농도의존성에 대한 indomethacin과 dexametasone의 영향을 검토한 결과 직선형의 비례커브로 영향을 미쳤다. 이러한 골대사의 지견을 바탕으로 대영전-자하거의 열수추출물의 시험관내 독성검사에서 $1-200\;{\mu}g/ml$의 농도에서는 독성이 없었으며, 또한, $300\;{\mu}g/ml$ 농도에서도 생쥐의 calvarial골에는 독성이 없었다. 대영전-자하거 extract는 PTH (2 units/ml), MCM (5%, v/v), $rhIL-1{\alpha}$ (1 ng/ml) $1,25(OH)_2D_3$ (10 ng/ml)처리에 대해서 그리고 $IL-1{\alpha}$와 $IL-1{\beta}$-유발 collagenolysis에 대해서도 보호효과가 있었다. 대영전-자하거extract을 1시간동안 전처리와 후처리에서 콜라겐분해에 약간의 보호활성이 있었으며 $IL-1{\alpha}$와 $IL-1{\beta}$에 의해 유발되는 콜라겐분해에 보호활성이 보였다. 1시간동안 전처리는 콜라겐분해를 감소시키며, 대영전-자하거 extract는 gelatinase효소를 저해하였으며 PTH, $1,25(OH)_2D_3$, $IL-1{\beta}$ 및 $IL-1{\alpha}$로 유발된 효소활성화가 저해되었다. 즉, 대영전-자하거 extracts는 $IL-1{\alpha}-$와 $IL-1{\beta}$에 의해 촉진되는 골재흡수에 효과적이었으며, 비스테로이드성 항염증제제 (indomethacin 과 dexamethasone)에 의한 골재흡수방지 효과와 유사하였다. 이러한 결과는 대영전-자하거extract가 골다공증치료에 효과적임을 나타내는 것이다.

• 치위생과학회지
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• 제12권1호
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• pp.71-77
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• 2012

본 연구는 월경주기에 따른 치주조직의 변화에 관한 예비연구로, 건강한 치주조직을 가지고 있고 월경주기가 일정한 20대 여성 7명과 남성 3명을 대상으로 4주간 8회 추구조사를 하였다. 시진상 치주조직의 상태는 건강하므로 치은열구액 내 바이오마커의 변화를 기준 변수로 하여, 상악전치부 치은열구액 내 MMP-9과 MMP-8, IL-$1{\beta}$의 농도를 측정하여 비모수 검정방법으로 분석하였다. 그 결과, 1. 여성대상자에서 월경시기, 배란추정시기에 각 염증지표들이 상승하는 추세를 보였으나 변화정도는 유의하지 않았다. 2. 성별에 따른 각 염증지표들의 차이는 유의하지 않았으며, MMP-9, MMP-8의 농도는 차이가 없었으나 IL-$1{\beta}$의 농도가 남성에서 유의하게 높았다(p=0.03). 3. 검사시점별 각 염증지표들의 상관관계는 강하거나 상당한 강한 양적 선형관계를 나타내었고 배란추정 시기와 월경시기에 상관계수가 더 높게 나타났다. 4. MMP-8과 IL-$1{\beta}$의 관계는 모든 검사시점에서 유의하였으나 MMP-9의 경우, MMP-8과 IL-$1{\beta}$의 상관관계가 유의하지 않은 시점도 있었다. 따라서, 여성대상자도 월경주기에 따른 변화정도가 남성대상자와 유의한 차이가 없으므로 치주병 위험요인에 따른 치주조직 변화의 추구조사에 참여할 수 있는 근거가 마련되었다. 또한 검사지표 중에 MMP-8이 모든 시점에서 다른 지표와 유의하고 강한 상관관계를 나타내어 대표 바이오마커로 적합할 것으로 사료되었다.

• Journal of Acupuncture Research
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• 제27권4호
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• pp.39-53
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• 2010

목적 : 퇴행성 관절염은 염증성 사이토카인인 IL-$1\beta$에 의해 연골관절이 파괴되고 이로 인해 염증성 사이토카인이 더욱 증가하는 질환이다. 퇴행성 관절염을 치료하기 위해서는 연골 파괴를 가속화시키는 catabolic cytokines의 활성을 줄이고, 성장인자인 anabolic factor의 활성을 증가시는 연골 보호 작용이 있어야 한다. 본 연구에서는 독활 승마 처방(OAH19T)이 catabolic/anabolic 대사 조절에 어떤 영향을 미치는지와 그 신호 전달 기전에 대해 연구하였다. 또한 OAH19T를 구성하는 단미재 및 임상에서 사용되는 COX-2 inhibitor인 Celebrex(CEL)와 효능을 비교 실험하였다. 방법 : 배양된 세포에 IL-$1\beta$로 자극한 후 (1) glycosaminoglycan(GAG)의 분해 억제 정도, (2) OAH19T와 CEL에 대하여 MMP-1과 MMP-3의 유전자 발현 및 활성 억제, (3) Aggrecan 및 Aggrecanases의 유전자 발현 및 활성 억제, (4) OAH19T의 growth factor의 조절 능력, (5) MAPK pathway 등을 RT-PCR(reverse transcriptase-polymerase chain reaction), ELISA(Enzyme-linked immunosorbent assay), western blot, viability 측정을 통해 검증했다. 결과 : 사람 관절 세포에서 (1) 독활 승마 각각의 단미재, 임상에서 사용중인 셀레콕시브(CEL), 조인스보다 실험 약물(OAH19T)이 저농도에서 GAG 분해 억제 효과가 우수하였고, 부탄올로 분획한 OAH19B와는 동등한 효과를 보였다. (2) OAH19T는 IL-$1\beta$에 의하여 활성화된 MMP-1과 MMP-3의 발현을 모두 억제하였으나, CEL은 MMP-1의 발현은 억제하였으나 MMP-3의 발현은 억제하지 못하였다. (3) OAH19T는 IL-$1\beta$에 의하여 손상된 Aggrecan을 회복시켰으며 이는 활성화된 Aggrecanase-1과 Aggrecanase-2를 억제시킴으로써 나타난 결과이다. 그러나 CEL의 경우, 손상된 Aggrecan을 회복시키지 못하였다. (4) 배양된 세포는 IL-$1\beta$에 의하여 TGF-$\beta$II및 TGF-$\beta$ receptor II의 발현이 억제되었으나, OAH19T는 TGF-$\beta$II및 TGF-$\beta$ receptor II의 발현을 회복시켜 OAH19T가 anabolic한 조절능력이 있음을 시사한다. 그러나 CEL의 경우 growth factor에 대한 조절 능력이 없었다. (5) 대사 조절 작용에 대한 기전으로서 MAPK pathway에 대해서 연구한 결과 IL-$1\beta$에 의하여 유도된 pERK, pp38 kinase의 활성은 억제하였고, pJNK의 활성은 변하지 않았다. 또한 OAH19T는 연골 세포에 독성이 없었으며 IL-$1\beta$에 의해 유도된 세포 증식만을 억제시켰다. 이 결과로, OAH19T가 OA chondrocyte의 탈분화 및 세포 고사를 억제하여 연골보호 및 회복 효과가 있음을 알 수 있었다. 결론 : OAH19T는 이를 구성하는 단미재 및 CEL보다 연골보호 효과가 월등하였고, 이러한 연골보호 효과는 catabolic cytokines/growth factors의 균형으로 대사조절을 통해 연골세포의 탈분화 및 세포 고사를 억제하여 연골보호 및 회복 효과가 있음을 알 수 있었다.

• 한국식품영양학회지
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• 제21권1호
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• pp.1-6
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• 2008

Job's Tears(Yul-Moo) is a grass crop long-used as a traditional medicine; it is also a nourishing food. There are reports of its anti-inflammatory, stomachic, antiallergic activity, and antispastic effects and Job's Tears has been used in China to treat rheumatism, and neuralgia although its warts, rheumanism remains unclear. Thus, the present study was performed to investigate the in vitro effect of Job's Tears extracts on immune function. Here mouse splenocyte proliferation and cytokine production$(IL-1{\beta},\;IL-6,\;TNF-{\alpha})$ by peritoneal macrophages cultured with ethanol and water extracts of Job's Tears were examined. splenocytes proliferation increased with Job's Tears water extracts supplement at concentrations investigated The cytokine production$(IL-1{\beta},\;IL-6,\;TNF-{\alpha})$ by ELISA using a cytokine kit And $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production increased water extracts supplementation. This in vitro study suggests that supplementation with Job's Tears water extracts may enhance immune function by regulating the splenocyte proliferation and enhancing cytokine production of activated macrophages.

• 한방재활의학과학회지
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• 제23권2호
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• pp.73-83
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• 2013

Objectives : This study was performed to investigate the effects of Foeniculum Vulgare(FV) extract on the anti-inflammatory of lipopolysaccharide(LPS) exposed rats. Methods : We divided LPS exposed Sprague-Dawley rats into 4 groups. They were control group, feed with 100 mg/kg, 200 mg/kg, 300 mg/kg FV groups. They were administered for 6 weeks. We measured the concentration of plasma interleukin-1${\beta}$(IL-1${\beta}$), plasma interleukin-6(IL-6), plasma tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), plasma interleukin-10(IL-10), the concentration of liver IL-1${\beta}$, IL-6, TNF-${\alpha}$ and IL-10. Results : 1. Plasma IL-1${\beta}$, plasma IL-6 and plasma TNF-${\alpha}$ concentration increased rapidly at 2hours after LPS injection and maintained high levels at 5hours after LPS injection. The concentration of these cytokines in the FV extract groups showed lower values than control group(P<0.05). 2. The concentration of Plasma IL-10 in FV extract groups showed higher values than control group at all times(P<0.05). 3. The concentration of liver IL-1${\beta}$ and IL-6 in FV extract groups showed lower values than control group(P<0.05). The concentration of liver TNF-${\alpha}$ in FV extract groups showed a tendency to decrease and that of liver IL-10 in FV extract groups showed a tendency to increase; however, these values showed no significantly different. Conclusions : In inflammatory response by LPS derivation, the FV gives positive effect.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2006년도 Proceedings of The Convention of The Korean Society of Applied Pharmacology
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• pp.103-115
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• 2006

[ ${\beta}-Glucan$ ] is a glucose polymer that has linkage of ${\beta}-(1,3)$, -(1,4) and -(1,6). As exclusively found in fungal and bacterial cell wall, not in animal, ${\beta}-glucans$ are recognized by innate immune system. Dendritic cells (DC) or macrophages possesses pattern recognition molecule (PRM) for binding ${\beta}-glucans$ as pathogen-associated molecular pattern (PAMP). Recently ${\beta}-glucans$ receptor was cloned from DC and named as dectin-l which belongs to type II C-type lectin family. Human dectin-l is consisted of 7 exons and 6 introns. The polypeptide of dectin-l has 247 amino acids and has cytoplasmic, transmembrane, stalk and carbohydrate recognition domains. Dectin-l could recognize variety of beta-l,3 and/or beta-l,6 glucan linkages, but not alpha-glucans. In our macrophage cell line culture system, dectin-l mRNA was detected in RA W264.7 cells by reverse transcription-polymerase chain reaction (RT-PCR). Dectin-l was also detected in the murine organs of spleen, thymus, lung and intestines. Treatment of RA W264.7 cells with ${\beta}-glucans$ of Ganoderma lucidum (GLG) resulted in increased expression of IL-6 and $TNF-{\alpha}$ in the presence of LPS. However, GLG alone did not increase IL-6 nor $TNF-{\alpha}$ These results suggest that receptor dectin-l cooperate with CD14 to activate signal transduction that is very critical in immunoresponse.

• 한국수의병리학회지
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• 제3권1호
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• pp.15-25
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• 1999

To elucidate the mechanism of age-related development in FGS/NgaKIST mice with spontaneous glomerulosclerotic lesion, we examined expression and localization of various cytokine mRNA in the kidney in the progression of diseases. This mouse model is the first to develop spontanously occuring glomerosclerotic lesion in the kidney. In this study, we detected the up-regulation of local cytokine genes such as IL-1$\beta$, IL-2, IL-6, IL-10, TNF-$\alpha$, TGF-$\beta$, and IFN- $\gamma$ in the kidneys. In RT-PCR and Southern blot analysis, we detected gradual expressions of cytokine mRNA of IL-1$\beta$, IL-2, IL-6, IFN- $\gamma$, and TNF $\alpha$ mRNA during the course of disease. Other cytokines including IL -10 and TGF -$\beta$ were found to be appeared the slightly expressed level at 3 to 12 weeks before onset of inflammatory lesion but they are highly expressed at the end-stage of the disease accompaning high proteinurea and wasting. In situ RT-PCR, each cytokine mRNA were specifically localized in a variety of cells including mesangial, endothelial, parietal epithelial, tubular epithelial, arterial muscle cell, and infiltrated inflammatory cells. In addition, TNF - $\alpha$was detected moderately in the visceral and parietal epithelial cell, but weakly in endothelial and mesangial cells, whereas IL-1 $\beta$ and IL -6 were strong in mesangial regions. IL-6 and TNF- $\alpha$ was highly localized in the damaged proximal and collecting tubules. Especially, TGF -$\beta$ mRNA was highly found in mesangial cells within glomerulus and interstitium during the end-stage of this disease.. These results indicate that pro inflammatory cytokines such as IL-1 $\beta$, IL-2, IL-6, and TNF- $\alpha$ were gradually expressed from the early stage of this disease to the end-stage, and that IL-10 and TGF-$\beta$ may be important in the accumulation of extracellular matrix(ECM) within glomerulus and periglomerular fibrosis in the progression of this disease as well as tissue destruction in end-stage of this disease.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2701-2705
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• 2015

Chondrosarcoma, the second most common type of bone malignancy, is characterized by distant metastasis and local invasion. Previous studies have shown that treatment by pulsed electromagnetic field (PEMF) has beneficial effects on various cancer cells. In this study, we investigated the effects of PEMF applied for 3 and 7 days on the matrix metalloproteinase (MMP) levels in chondrosarcoma SW1353 cells stimulated with two different doses of $IL-1{\beta}$. SW1353 cells were treated with (0.5 and 5 ng/ml) $IL-1{\beta}$ and PEMF exposure was applied either 3 or 7 days. MMP-9 and TIMP-1 levels were measured in conditioned media by enzyme-linked immunosorbent assay. The results were relative to protein levels. Statistical analyses were performed using one-way analysis of variance (ANOVA). P<0.05 was considered significant. PEMF treatment significantly decreased MMP-9 protein levels in human chondrosarcoma cells stimulated with 0.5 ng/ml $IL-1{\beta}$ at day 7, whereas it did not show any effect on cells stimulated with 5 ng/ml $IL-1{\beta}$. There was no significant change in TIMP-1 protein levels either by $IL-1{\beta}$ stimulation or by PEMF treatment. The results of this study showed that PEMF treatment suppressed $IL-1{\beta}$-mediated upregulation of MMP-9 protein levels in a dual effect manner. This finding may offer new perspectives in the therapy of bone cancer.