• 한국식품영양과학회지
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• 제45권7호
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• pp.929-937
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• 2016

본 연구에서는 랫트를 이용한 제2형 당뇨 동물모델로 같은 혈당조절 효과가 나타나는지 검토하고 이러한 효과가 당화 혈색소를 포함한 최종당화산물(advanced glycation end products, AGEs)과 어떤 상관관계가 있는지 또한 단백질과 당화를 촉진해 당화혈색소 생성의 원인 중 하나인 산화적 스트레스와 관련된 기전을 규명하고자 하였다. 기존의 db/db 마우스에서 실험한 결과와 마찬가지로 랫트를 이용한 제2형 당뇨모델에서도 가시오가피 추출물의 섭취는 혈당을 강하시키고 homeostasis model assessment(Homa-IR)를 감소시켜 인슐린 저항성 개선에 도움을 주는 것으로 확인되었다. 특히 혈중 당화혈색소량의 감소가 두드러졌는데 이는 산화적 스트레스 감소로 인한 지질과산화물 생성의 억제가 중요한 원인으로 생각되며 이와 관련된 혈중 사이토카인 IL-$1{\beta}$와 TNF-${\alpha}$의 농도도 감소한 것으로 나타났다. 당화혈색소는 산화적 스트레스에 의해 최종당화산물로 전환이 되어 인슐린 저항성 세포의 protein kinase C(PKC)를 활성화하여 transforming growth factor(TGF)-${\beta}$를 생성하는데 가시오가피 추출물의 섭취는 최종당화산물의 농도, PKC 그리고 TGF-${\beta}$ 모두를 억제하는 것으로 확인되었으며, 이것은 가시오가피 추출물 성분이 PKC와 TGF-${\beta}$에 직접 작용하기보다는 신호전달체계의 상위에 존재하는 최종당화산물을 억제하여 나타난 결과로 생각한다. 향후 연구에서는 가시오가피 추출물을 분획화하여 어떤 성분에 의하여 당화혈색소와 최종당화산물 생성을 억제하는지에 대한 구체적인 실험이 이루어져야 할 것으로 여겨진다.

• 대한본초학회지
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• 제27권6호
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• pp.115-122
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• 2012

Objectives : This study evaluated activities and ingredient contents concerning extracts according to extraction solvents of Insampaedok-san (IS, Renshen bai du-san). Methods : The herbal constituents of IS were extracted with water and 70% ethanol at $100^{\circ}C$ for 2 hr. Using the HPLC system, the six ingredient contents of different solvent extracts of IS were analyzed. The nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) production and proinflammatory cytokines were measured in RAW264.7 cells stimulated with lipopolysaccharide (LPS). The macrophage-derived chemokine (MDC/CCL22) and regulated on activation normal T-cell expression and secreted (RANTES/CCL5) production were measured in HaCaT and BEAS-2B cells stimulated tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). The activities of glycerol-3-phosphate dehydrogenase (GPDH) and leptin level were measured in 3T3-L1 cells. Results : The calibration curves showed good linearity ($r^2$=1.0000) for different concentration ranges. The contents of liquiritin, naringin, hesperidin, neohesperirin and glycyrrizin in 70% ethanol extracts of IS were relatively higher than that of water extract, however the content of ferulic acid in 70% ethanol and water extract of IS were similar. The extraction solvents of water and 70% ethanol were evaluated inhibitory effect on the production of NO, $PGE_2$, TNF-${\alpha}$ and IL-6 in RAW 264.7 cells. Their extractions were inhibitory effect on production of MDC/CCL22 and RANTES/CCL5 in HaCaT cell and BEAS-2B cell, respectively. In addition, evaluated reduced on GPDH activity and leptin level in 3T3-L1 preadipocyte cell. Conclusions : Our results suggest that IS extracts were inhibitory effects of disease such as inflammation, allergies and obesity.

• 대한한방부인과학회지
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• 제15권4호
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• pp.61-75
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• 2002

유전자 재조합으로 제조한 사람 $interleukin-1{\beta}$ $(rhIL-1{\beta})$는 생쥐의 calvarial 골세포계에서 분리한 골아세포에 여러 가지 조절기능을 갖는 것으로 알려져 있다. 본 연구에서 $rhIL-1{\beta}$가 농도의존적으로 골세포에 영향을 주는지 해명하기 위하여 배양된 골아세포의 세포증식과 prostaglandin $E_2$합성 그리고 plasminogen activator활성에 대한 영향을 검토한 결과 이들을 촉진하였다. 그러나 비타민D에 따라 반응하는 골아세포의 특징으로 알려진 osteocalcin생합성과 alkaine phosphatase활성의 유도생성은 $rhIL-1{\beta}$에 의해 오히려 길항적이었다. 이러한 결과는 골세포대사의 병리학적인 조절과정에서 $IL-1{\beta}$가 골다공증의 병리학적 역할을 규명하는 새로운 결과이다. $IL-1{\beta}$에 의한 골흡수현상이 생쥐의 calvarial골세포에서 calcitonin처리로 크게 억제되어, 결과적으로 이러한 결과는 $IL-1{\beta}$에 의해 유발되는 골재흡수란 osteoclast에 의한다는 사실을 시사하였다. 한편, 한방에서 골다공증치료와 예방에 사용되는 대영전-자하거추출물의 기능을 해명하기 위하여, $IL-1{\beta}$-유발 $PGE_2$합성만을 특이적으로 저해하였다. 또한, 대영전-자하거 extract을 1시간 동안 여러 가지 농도로 전처리하고 다음으로 $PGE_2$-유도시약을 처리한 결과, $PGE_2$합성을 억제하였으며 동시에 $IL-1{\beta}$에 의해 유도된 plasminogen 의존적인 fibrinolysis을 억제하는 보호효과가 인정되었다. 한편, calcitonin처리가 $IL-1{\beta}$-촉진 골재흡수에 대한 저해활성을 보였으며 이러한 결과들은 calcitonin과 대영전-자하거 extract이 osteoclast매개성 골재흡수의 억제에 핵심적인 역할을 함을 시사하며 한방치료제로서의 근거를 제시하였다고 사료된다.

• 대한화장품학회지
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• 제30권2호
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• pp.227-233
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• 2004

자외선이 피부에 지속적으로 조사되면 썬번, 염증, 광노화와 같은 다양한 부작용이 생기게 된다. 따라서 광손상에 대한 보호작용은 점점 중요성이 인식되고 있으며, 천연 식물추출물에서 자외선에 대한 광보호효과가 있는 안전하고 효과적인 물질개발에 대한 연구가 진행되고 있다. 본 연구는 자외선에 의해 유도된 피부손상에 대한 보호효과가 우수한 천연식물추출물에 대한 것이다. 향나무, 능소화, 비자추출물에서 자외선에 의해 생성되는 라디칼에 대한 항산화효과, MMP 발현 및 활성 저해, 염증관련 사이토카인인 인터루킨 1알파, 6, 프로스타글란딘 E$_2$ 생성저해효과 등으로 피부세포보호 효과를 연구하였다. 실험결과 천연추출물 중 향나무추출물과 능소화추출물이 프리라디칼 및 슈퍼옥사이드 라디칼 소거효과가 우수하게 나타났으며 피부 콜라겐과 같은 메트릭스를 분해하는 효소인 MMP-1의 활성 및 발현 저해효과는 섬유아세포에서 UVA 조사에 의한 실험에서 우수하게 나타났으며, 피부세포 배양액에 대해 zymography를 실시하여 활성이 감소됨을 확인하였다. 피부 각질형성세포에서 자외선에 의해 유도된 염증관련 사이토카인인 인터루킨 6의 발현량 실험에서도 무처리군에 비해 향나무추출물이 인터루킨 6을 30% 정도 저해효과가 나타났으며, 염증반응 중 cyclooxygenase(COX)에 의한 경로에서 생성되는 프로스타글란딘 E$_2$의 생성량도 감소시켰다. 사람피부에서 SLS (0.5%) 첩포로 유발된 자극성 피부염의 항염증 효과 평가 시 SLS에 의해 유발되는 자극정도가 피검자의 피부상태에 따라 다양하게 나타났으며, 향나무 추출물 함유 에멀젼 제품 도포 실험에서는 피부 홍반 완화 효과와 피부장벽 회복효과가 우수하게 나타났다. 이상의 결과로 향나무추출물은 자외선 조사 및 SLS에 의한 피부손상에 대한 피부세포보호작용이 우수하여 광노화에 대응하는 자극완화 소재로서의 화장품 응용 가능성을 확인하였다.

• 생명과학회지
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• 제27권12호
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• pp.1437-1444
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• 2017

본 연구에서는 갈조류인 큰열매모자반 에탄올 추출물(Ethanol extract of Sargassum Macrocarpum, EESM)의 항염증 활성을 조사하였다. Lipopolysaccharide (LPS)로 염증이 유도된 RAW 264.7 대식세포에서 EESM에 의한 항염증 효과를 조사한 결과 EESM은 nitric oxide (NO)와 prostaglandin $E_2$ ($PGE_2$)의 분비를 억제하는 결과를 보였고, 이는 inducible NO synthase (iNOS)와 cyclooxygenase-2 (COX-2)의 발현 역시 억제하였다. 또한 전염증성 사이토카인인 tumor necrosis factor-alpha ($TNF-{\alpha}$)와 interleukin 1 beta ($IL-1{\beta}$)의 발현도 억제하였다. 이러한 염증반응이 어떤 신호경로를 통해 일어나는지 알아보기 위해 nuclear factor kappa B ($NF-{\kappa}B$), phosphoinositide-3-kinase (PI3K)/Akt 그리고 mitogen-activated protein kinases (MAPKs) 신호전달 경로를 조사한 결과 EESM에 의해 $NF-{\kappa}B$가 세포질에서 핵으로 이동과 Akt 단백질의 인산화가 억제되었고 MAPK에 속하는 kinase 중 ERK의 단백질 인산화가 억제되었다. 따라서 EESM이 $NF-{\kappa}B$ 신호계를 포함한 PI3K/Akt 및 MAPK/ERK 신호경로를 동시에 관여하고 있음을 알 수 있었다. 또한 heme oxygenase-1 (HO-1)과 그 전사 인자인 nuclear factor-E2-related factor 2 (Nrf2)의 단백질 발현에 미치는 영향을 분석한 결과 EESM에 의해 HO-1 및 Nrf2의 발현이 증가됨을 보였다. 본 연구 결과 EESM은 높은 항염증 활성을 갖는 것으로 확인되였으며 향후 잠재적인 기능성 소재로서 유용하게 활용될 수 있을 것으로 사료된다.

• 대한한의학회지
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• 제34권3호
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• pp.69-85
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• 2013

Objectives: This study investigated the anti-osteoarthritic effects of Kyejiinsam-tang (hereinafter referred to KIT) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods: Anti-oxidative effects of KIT were measured by scavenging activities of DPPH, reactive oxygen species (ROS) and nitric oxide (NO). Scavenging activities of anti-oxidation in lipopolysaccharide (LPS)-treated RAW 264.7 cells were also measured for inhibitory effects against the production of inflammatory mediators (tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, interleukin-6). Osteoarthritis was induced in rats by injecting MIA in the knee joint. Rats were divided into a total of 4 groups (n=6). The normal group were not treated at all without inducing osteoarthritis whereas the control group were induced for osteoarthritis by MIA and oral medicated physiological saline per day. The positive comparison group was injected with MIA and after 7 days, 2 mg/kg of Indomethacin. The experimental group was injected with MIA and after 7 days was medicated with 34 mg/kg of KIT. Indomethacin and KIT were orally-medicated for each substance a total of 4 weeks, once per day. Weight-bearing on hind legs was measured every week after MIA injection. At the end of the experiment (5 weeks after MIA injection), micro CT (computed tomography)-arthrography and histopathological examinations on the articular structures of knee joint were performed. The effect on inflammatory cytokines and immunological cells in synovial fluid was measured. Volume of cartilage was measured by micro CT-arthrography. Injury to synovial tissue was measured by H & E (hematoxylin and eosin), Safranin-O immunofluorescence. Results: 1. Cytotoxicity against hFCs was insignificant. 2. KIT showed the potent full term for DPPH. 1. NO was significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and ROS was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 2. IL-6 and IL-$1{\beta}$ were significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and TNF-${\alpha}$ was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 1. In hind legs weight-bearing measurement, level of weight increased. 2. Functions of liver and kidney were not affected. 3. IL-$1{\beta}$ was significantly reduced and TNF-${\alpha}$, IL-6 were also reduced but not significantly. 4. PGE2 (prostaglandin E2), LTB4 (leukotriene B4) were significantly reduced in the KIT group. 5. MMP-9 (matrix metalloproteinase-9), TIMP-1 (tissue inhibitor of metalloproteinases-1) and Osteocalcin were significantly reduced in the KIT group. 6. Destruction of cartilage on micro CT arthrography was reduced but had no significant differences. 7. Histopathologically, injury to synovial membrane of the KIT group was decreased and proteoglycan content of KIT group was increased. Conclusions: According to this study, Kyejiinsam-tang has inhibiting effect on the progression of arthritis in MIA-induced osteoarthritis rat. Kyejiinsam-tang has anti-oxidants and anti-inflammation effects, and is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

• Asian-Australasian Journal of Animal Sciences
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• 제31권6호
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• pp.784-790
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• 2018

Objective: The genetic effects of an individual on the phenotypes of its social partners, such as its pen mates, are known as social genetic effects. This study aims to identify the candidate genes for social (pen-mates') average daily gain (ADG) in pigs by using the genome-wide association approach. Methods: Social ADG (sADG) was the average ADG of unrelated pen-mates (strangers). We used the phenotype data (16,802 records) after correcting for batch (week), sex, pen, number of strangers (1 to 7 pigs) in the pen, full-sib rate (0% to 80%) within pen, and age at the end of the test. A total of 1,041 pigs from Landrace breeds were genotyped using the Illumina PorcineSNP60 v2 BeadChip panel, which comprised 61,565 single nucleotide polymorphism (SNP) markers. After quality control, 909 individuals and 39,837 markers remained for sADG in genome-wide association study. Results: We detected five new SNPs, all on chromosome 6, which have not been associated with social ADG or other growth traits to date. One SNP was inside the prostaglandin $F2{\alpha}$ receptor (PTGFR) gene, another SNP was located 22 kb upstream of gene interferon-induced protein 44 (IFI44), and the last three SNPs were between 161 kb and 191 kb upstream of the EGF latrophilin and seven transmembrane domain-containing protein 1 (ELTD1) gene. PTGFR, IFI44, and ELTD1 were never associated with social interaction and social genetic effects in any of the previous studies. Conclusion: The identification of several genomic regions, and candidate genes associated with social genetic effects reported here, could contribute to a better understanding of the genetic basis of interaction traits for ADG. In conclusion, we suggest that the PTGFR, IFI44, and ELTD1 may be used as a molecular marker for sADG, although their functional effect was not defined yet. Thus, it will be of interest to execute association studies in those genes.

• IMMUNE NETWORK
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• 제11권3호
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• pp.175-181
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• 2011

Background: CM1 (centrocyte/-blast marker 1) was defined by a mAb against concavabalin-A (ConA) activated PBMC. It is expressed in germinal center of human tonsil and on the surface of activated PBMC as well as cancer cells. Recently, increased productions of pro-inflammatory mediators were detected from activated PBMC by CM1 ligation. Methods: However, there is a limitation to explain the exact role of CM1 on inflammation and its related mechanisms, since the identity of CM1 is still not clarified. In our previous study, we have already confirmed that soluble form of CM1 was produced by Raji. Therefore, we performed Q-TOF analysis after immunoprecipitation of concentrated Raji culture supernatant using anti-CM1 mAbs. Results: As a result, we found that CM1 is identical to enolase-1(ENO1), a glycolytic enzyme, and we confirmed that results by silencing ENO1 using siRNA. It was also confirmed through competition assay between anti-CM1 and anti-ENO1 mAbs. Finally, we investigated the possible role of CM1 in inflammatory response and cancer. The ligation of CM1 on Raji cells with anti-CM1 mAbs induces the extensive production of prostaglandin $E_2(PGE_2)$. In addition, the increased activity of matrix metalloproteinase (MMP)-2/9 was shown in NCI-N87, stomach cancer cell line by CM1 stimulation. Conclusion: CM1 is identical to ENO1 and it might be an important role in the regulation of inflammatory responses.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.388-394
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• 2009

The cytokines which is produced by allergen-specific T helper (Th) cells play a pivotal role in the pathogenesis of asthma. Asthma is caused by exaggerated T-helper 2 (Th2)-based immune responses. It is suggested that controlling such Th2-based response is necessary for asthma therapy. The current therapies for asthma focus primarily on control of symptoms and suppression of inflammation, without affecting the underlying cause. So, we examined that anti-asthmatic drugs might have play a certain role in Th2/Th1 balance. Splenocytes isolated from ovalbumin (OVA)-sensitized mice cultured with anti-asthmatic drugs. It is well known that Th2 and Th1 immune responses can balance one another, as Th2 mediators suppress Th1 responses and Th1 mediators similarly inhibit Th2 responses. But salmeterol inhibits both of Th1 and Th2 mediators, which salmeterol is a suppressor of immune responses not only a suppressor of Th2-based immune responses. Aminophylline is a weak suppressor of immune responses. But ipratropium and cromoglycate don't have any suppressor effect to Th2-driven responses. They only have suppressor effect to Th1 immune responses. Salmeterol, ipratropium, aminophylline, and cromoglycate augmented mRNA levels of CRTH2, EP2, and IP2 receptors in OVA-sensitized splenocytes. It is well known that the up-regulation of CRTH2 - $PGD_2$ receptor - results in restraint of eosinophil recruitment and that the increment of IP and EP2 - $PGI_2$ and $PGE_2$ receptor, respectively - may induce the accumulation of cAMP that decrease the effector function of T cells. Moreover salmeterol and cromoglycate increase the mRNA expression of $PGD_2$ synthase. These findings indicate that anti-asthma agents may alleviate the immunological responses that cause the asthmatic diseases.

• International Journal of Oral Biology
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• 제30권2호
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• pp.47-57
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• 2005

Leptin, the product of the obese gene, is a circulating hormone secreted primarily from adipocytes. Several results suggest that leptin is important mediators of bone metabolism. The present study was undertaken to determine the effects of leptin on anti-osteoclastogenesis using murine precursors cultured on Ca-P coated plates and on the production of osteoprotegerin (OPG) in osteoblastic cells. Additionally, this study examined the possible involvement of prostaglandin $E_2\;(PGE_2)$/protein kinase C (PKC)-mediated signals on the effect of leptin on anti-osteoclastogenesis to various culture systems of osteoclast precursors. Osteoclast generation was determined by counting tartrate-resistant acid phosphatase positive [TRAP (+)] multinucleated cells (MNCs). Osteoclastic activity was determined by measuring area of resorption pits formed by osteoclasts on Ca-P coated plate. The number of 1,25-dihydroxycholecalciferol $(1,25[OH]_2D_3)$- or $PGE_2$-induced TRAP (+) MNCs in the mouse bone marrow cell culture decreased significantly after treatment with leptin. The number of receptor activator of NF-kB ligand (RANKL)-induced TRAP (+) MNCs in M-CSF dependent bone marrow macrophage (MDBM) cell or RAW264.7 cell culture decreased significantly with leptin treatment. Indomethacin inhibited osteoclast generation induced by $1,25[OH]_2D_3$ and dexamethasone, however, no significant differences were found in the leptin treated group when compared to the corresponding indomethacin group. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, inhibited osteoclast generation induced by $1,25[OH]_2D_3$. The number of TRAP (+) MNCs decreased significantly with treatment by PMA at concentrations of 0.01 and $0.1{\mu}M$ in culture. Leptin inhibited PMA-mediated osteoclast generation. Isoquinoline-5-sulfonic 2-methyl-1-piperazide dihydrochloride (H7) had no effect on osteoclast generation induced by $1,25[OH]_2D_3$. Cell culture treatment with leptin resulted in no significant differences in osteoclast generation compared to the corresponding H7 group. Indomethacin showed no significant effect on TRAP (+) MNCs formation from the RAW264.7 cell line. PMA inhibited TRAP (+) MNCs formation induced by RANKL in the RAW264.7 cell culture. H7 had no effect on osteoclast generation from the RAW264.7 cell line. There was no difference compared with the corresponding control group after treatment with leptin. $1,25[OH]_2D_3$- or $PGE_2$-induced osteoclastic activity decreased significantly with leptin treatment at a concentration of 100 ng/ml in mouse bone marrow cell culture. Indomethacin, PMA, and H7 significantly inhibited osteoclastic activity induced by $1,25[OH]_2D_3$ in mouse bone marrow cell culture. No significant differences were found between the leptin treated group and the corresponding control group. The secretion of OPG, a substance known to inhibit osteoclast formation, was detected from the osteoblasts. Treatment by leptin resulted in significant increases in OPG secretion by osteoblastic cells. Taken these results, leptin may be an important regulatory cytokines within the bone marrow microenvironment.