• 한국수산과학회지
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• 제48권4호
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• pp.439-446
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• 2015

Inflammation is a protective response to infection or injury. However, prolonged inflammation can contribute to the pathogenesis of many diseases, such as cancer, diabetes, arthritis, atherosclerosis, and Alzheimer's disease. Recent studies have shown that activated macrophages, inflammatory effector cells, can react to tissue insults in a polarized manner, in which their phenotypes are polarized into two major subtypes, categorized as M1 or M2. Classical M1 activation involves the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-${\alpha}$, and free radicals, while M2 or alternative activation is an anti-inflammatory phenotype involved in homeostatic processes, such as wound healing, debris scavenging, and the dampening of inflammation via the production of very low levels of pro-inflammatory cytokines and high levels of anti-inflammatory mediators, including IL-10. As part of our ongoing effort to isolate anti-inflammatory compounds from seaweeds, we investigated the effects of phlorotannins isolated from the brown alga Ecklonia stolonifera on macrophage polarization. Mouse peritoneal macrophages were treated with various concentrations of the extracts, and real-time RT-PCR analyses were performed to examine the expression of polarization markers: IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ for M1 and arginase-1, peroxisome proliferator-activated receptor (PPAR)-${\gamma}$, found inflammatory zone-1 (Fizz-1), chitinase 3-like 3 (Ym1), and$Kr{\ddot{u}}ppel$-like factor 4 (Klf-4) for M2. The pretreatment of cells with eckol, dieckol, and phlorofucofuroeckol-A (PFF-A), isolated from the ethyl acetate fraction of E. stolonifera ethanolic extract, potentiated the anti-inflammatory M2 phenotype of the macrophages. These results indicate that phlorotannins derived from E. stolonifera can be used to enrich macrophages with markers of the M2 anti-inflammatory state.

• Journal of Acupuncture Research
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• 제29권1호
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• pp.89-101
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• 2012

Objectives : The purpose of this study was find out the therapeutic effects of its exclusive use on the rat with allergic rhinitis. Materials and Methods : Thirty Sprague-Dawley rats were divided into three group : normal group, control group and sample group. To induce the allergic rhinitis in control group and sample group, rats were sensitized intraperitoneally with 0.1% ovalumin solution 3 times at intervals of 1 week. Then intranasal sensitization was performed by diffusing 0.1% ovalumin solution 3 times at intervals of 2 days. After that time, rats in the sample group were administered by $Yonghyang$($LI_{20}$) subcutaneously to treat the inflammation. Results : 1. The anti-oxidant effects of $Hwangryunhaedok-tang$ extract was dose-dependantly increased. 2. The RAW 264.7 cells were treated with LPS for 1 hours prior to the addition of indicated concentrations ($0.4,-1.0mg/m{\ell}$) of HHT, and the cells were further incubated for 24 hours. The LPS-induced iNOS mRNA expression and NO production were dose-dependantly decreased in HHT treated RAW 264.7 cells. 3. The number of eosinophil in HP noticeably decreased than CON and this decrease had probability. The infiltration of eosinophil in HP noticeably decreased than CON. 4. The damaged mucosa as disruption of cilia in respiratory cell and vacant mucose secreting cell were increased CON, but HP same as normal configuration. Decrease of PAS positive cell were shown in CON, but goblet cell occupied with neutral mucous were shown in HP. Decrease of mucosal stress(HSP70). Decrease of perennial sign(PPAR-${\gamma}$). Decrease of icthing and sneezing intricate neurotransmitter-(substance P). 5. The anti-inflammation of HHT pharmacopuncture for AR caused mucosa comes to result as belows. Decrease of pre-inflammation cytokine(TNF-${\alpha}$). Decrease of transcription factor (NF-${\kappa}B$ p65). Decrease of transcription factor inhibitor(p-$I{\kappa}B$). Decrease of inflammation cytokine(iNOS). Conclusions : The results may suggest that administration treatment using $Hwangryunhaedok-tang$ pharmacopucnture decreases the inflammatory response on an animal model with allergic rhinitis.

• Journal of Acupuncture Research
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• 제29권1호
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• pp.115-125
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• 2012

Objectives : The purpose of this study is to observe the inhibitory effects of $Chrthami$ semen oil pharmacopuncture(CSOP) on CIA (collagen-induced arthritis) mice. Materials and Methods : Two types of experiments were conducted: $in$ $vitro$ assay, inhibition of MIF mRNA and TNF-${\alpha}$ mRNA expressions in synovial membranes was observed, and $in$ $vivo$ assay, $1{\mu}{\ell}/kg$ CSOP was injected every day to the left $Weizhong$ ($BL_{40}$) from day 3 to 21 after induction of CIA, and changes in paw edema, apical surface morphology, neovascularization in synovial membranes, fibrosis, pro-inflammatory cytokines production, Th-1 differentiation, and anti-inflammatory effect were investigated. Results : 1. In synoviocytes of the CIA mice treated with CSOP, MIF mRNA and TNF-${\alpha}$ mRNA expressions were down-regulated in a dose-dependent manner. 2. Paw edema of the CIA mice treated with CSOP was diminished. 3. Tissue injury in the synovial membranes, capillary distribution and fibrosis were reduced in CSOP-treated mice. 4. MIF, TNF-${\alpha}$, IL-6, MMP-9 expressions were repressed in CSOP-treated mice during the experiment to observe the inhibitory effect on cytokines production in early stage RA. 5. IL-12 and CD28 were reduced in CSOP-treated mice during the observation of inhibitory effect on Th 1 differentiation. 6. PPAR-${\gamma}$ was increased during the experiment to observe the anti-inflammatory effect of CSOP. Conclusions : The results may suggest that administration treatment using $Chrthami$ semen oil pharmacopuncture decreases the inflammatory response on an Animal Model with CIA.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권1호
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• pp.1-8
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• 2005

This study was aimed to characterize osteogenic potential of rat bone marrow stromal cells (BMSC) isolated with standard flushing method and investigate the plasticity of transdifferentiation between osteoblastic and adipocytic lineage of cultured BMSC. Unlike aspiration method in human, rat bone marrow was extracted by means of irrigation with culture media that elevates the possibility of co-extraction of committed osteoprogenitor, or preosteoblast or other progenitor cells of several types present inside bone marrow. The cultured stromal cells showed high ALP activity which is representative marker of osteoblast without any treatment. Osteogenic inducers such as Dex and BMP-2 were examined for the evaluation of their effect on osteogenic and adipocytic differentiation of stromal cells, because they function as osteoinductive agent in stromal cells, but simultaneously induce adipogenic differentiation. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity or mRNA expression of osteoblast markers such as osteopontin, bone sialoprotein, collagen type I and CbfaI, and in vitro matrix mineralization by von Kossa staining. Oil red staining method was used to detect adipocyte and adipocytic marker, aP2 and $PPAR{\gamma}2$ expression was examined using RT-PCR. It can be supposed that irrigation procedure resulted in high portion of already differentiation-committed osteoprogenitor cell showing elevated ALP activity and strong mineralization only under the supplement of $100{\mu}M$ ascorbic 2-phosphate and 10mM ${\beta}$-glycerophosphate without any treatment of osteogenic inducers such as Dex and BMP-2. Dex and BMP-2 seemed to transdifferentiate osteoprogenitor cells having high ALP activity into adipocytes temporarily, but continuous treatment redifferentiated into osteoblast and developed in vitro matrix mineralization. This property must be considered either in tissue engineering for bone regeneration, or in research of characterization of osteogenic differentiation, with rat BMSC isolated by the standard irrigation method.

• 생명과학회지
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• 제30권10호
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• pp.835-843
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• 2020

비만은 이제 선진국 뿐만 아니라 개발도상국에서도 가장 문제가 되는 대사성 질환이다. 최근 치료보다는 예방에 중점을 두는 예방의학 시대가 도래함에 따라, 인슐린 저항성 비만과 당뇨병 등의 대사 증후군을 예방하기 위한 천연물들이 큰 관심을 받고 있다. 특히, 베타글루칸은 면역계와 혈중 콜레스테롤 조절에 이로운 효과가 있는 것으로 알려져 있지만 비만에 미치는 영향에 대해서는 완전히 밝혀지지 않았다. 이에 본 연구에서는 β-1,3/1,6-glucan의 함량이 전체 글루칸 함량의 90% 이상 되는 자체 개발 흑효모 균주 SM-2001 추출물(폴리칸)이 3T3-L1 지방전구세포의 지방세포 분화에 미치는 영향을 조사하였다. 폴리칸은 지방전구세포에서 지방축적과 GPDH 효소 활성을 억제하는 것으로 나타났다. 이는 폴리칸이 세포 내에서 지방의 축적을 조절하는 전사인자인 PPARγ와 C/EBPα의 하향조절과 세포 내 에너지 센서 역할을 하는 AMPK 효소의 인산화를 유도함으로써 항비만 효과를 발현하는 것으로 확인되었다. 본 연구를 통해 폴리칸의 항비만 효과를 확인하였으며, 향후 비만과 대사성 질환을 예방할 수 있는 식의약 소재로써 그 활용가치를 더욱 높일 수 있을 것으로 기대한다.

• 대한한방소아과학회지
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• 제20권2호
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• pp.177-196
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• 2006

Objective : This experimental study was designed to determine the effects of BPT on obesity in vivo and in vitro. Methods : in vitro, BPTn extracts of various concentration(50, 100, 200 ${\mu}g/m{\ell}$) were added in 3T3-L1 cell. Adipocyte differentiation was measured by Oil Red O staining and Morphological examination. The expression of $C/EBP{\alpha}$ and $PPAR{\gamma}$ receptor was measured by western blot assay and RT-PCR in vivo, Rats were orally administered BPT daily for consecutive four weeks before poloxamer-407 induced hyperlipidemic state. The rats were sacrificed 24 hrs later for poloxamer-407 treated and then serum triglyceride, total cholesterol were measured ; Rats were orally administered BPT daily for consecutive four weeks before triton WR-1339 induced hyperlipidemic state. The rats were sacrificed 40 hrs later for triton WR-1339 treated and then serum triglyceride, total cholesterol were measured ; Rats with obesity were induced by the high fat-diet for six weeks and then serum triglyceride, total cholesterol, LDL-cholesterol, triglyceride, HDL-cholesterol, hydroxy radical, superoxide dismuatse activity were measured. Results : In vitro, The 3T3-L1 cells' differentiation was significantly decreased by BPT. The expression of $C/EBP{\alpha}$ and $C/EBP{\beta}$ was decreased by BPT. In vivo, BPT significantly reduced serum triglyceride, total cholesterol contents in poloxamer-407 treated rat. BPT significantly reduced serum triglyceride contents in Triton WR-1339 treated rat. Total cholesterol also reduced but did not show a significant change. BPT significantly reduced body weight gain of rat and adipose tissue mass of rats and serum triglyceride, LDL-cholesterol contents and significantly increased HDL-cholesterol, HTR(HDL-cholesterol/Total-cholesterol) in rats with obesity induced by the high fat-diet. BPT reduced blood lipid peroxide, hydroxy radical and increased superoxide dismuatse(SOD) activity.

• 한국식품과학회지
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• 제39권6호
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• pp.701-707
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• 2007

민간요법에서 항당뇨 및 항비만 효과가 있는 것으로 알려진 길경의 항당뇨 효과가 있는 지 여부를 in vitro에서 조사하기 위해서 길경을 70% 에탄올로 추출한 후 메탄올과 물을 섞은 용액으로 단계별로 XAD-4 column으로 분획하였다. 본 연구에서는 1) 3T3-L1 섬유아세포와 지방세포에서 길경의 추출 분획물이 인슐린처럼 작용하는 인슐린성 물질이거나, 2) 인슐린 작용을 향상시키는 인슐린 민감성 물질이거나, 또는 3) 포도당 자극에 의한 인슐린 분비를 향상시키거나, 4) 베타세포의 기능과 양을 증가시키는데 관여하는 유전자인 IRS-2, glucokinase, PDX-1의 mRNA 발현을 향상시키거나, 5) $\alpha-glucoamylase$ 활성을 억제하는 물질로 작용하는 지 여부를 조사하였다. 길경 추출 분획물은 인슐린성 물질로 작용하지 않았다. 반면에 0, 20와 100%메탄올층은 3T3-L1 지방세포에서 인슐린 자극에 의한 포도당 흡수를 증가시켰다. 이 분획층 중에서 특히 0%과 100% 메탄올 분획층은 분화 유도물질의 작용을 향상시켜 3T3-L1 섬유아세포에서 지방세포로의 분화 및 중성 지방의 축적을 증가시켰다. 그러므로 이들은 $PPAR-{\gamma}$ agonist로 작용하는 물질을 함유할 가능성이 매우 높다. 인슐린을 분비하는 세포인 Min6 세포에서 포도당 자극에 의한 인슐린 분비를 향상시키는 지 여부를 조사하였는데 20, 80 그리고 100% 메탄올층은 포도당 자극에 의한 인슐린 분비를 증가시켰다. 그 기전은 인슐린 분비와 베타세포의 증식에 관여하는 유전자의 IRS-2, glucokinase 그리고 PDX-1의 mRNA의 양을 증가시키는 것과 관련이 있다. 결론적으로 길경은 지방 세포의 분화를 촉진하는 물질, 인슐린 민감성을 향상시키는 물질 그리고 베타세포의 기능과 증식을 촉진시키는 물질을 함유하고 있으므로 우리나라 및 아시아의 사람들에서 많이 유발되는 비만을 동반하지 않은 당뇨병 및 인슐린 저항성의 치료와 예방에 중요한 역할을 할 것으로 사료된다.

• 한국식품위생안전성학회지
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• 제33권5호
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• pp.389-398
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• 2018

본 연구는 고려엉겅퀴 주정추출물을 가지고 제작된 임상시험용제품(CNTM)이 3T3-L1 지방세포 및 고지방식이로 유도된 비만 쥐에 미치는 항비만 효능 관찰을 통하여 체지방 개선 기능성식품을 개발하기위하여 인체적용시험 시료를 제작한 후, 인체적용시험전에 그 효력이 유지됨을 확인하기위해 수행되었다. 본 연구에 사용된 시료 CNTM은 $80{\sim}320{\mu}g/mL$ 농도에서 세포독성이 관찰되지 않았으며, 지방 축적억제 효능 및 지방세포 분화, 지질대사 관련 유전인자들을 유의적으로 변화시키는 것으로 확인되었다. 또한 동물실험에서 CNTM 처리에 의하여 체중의 감소를 확인하였으며 혈중지질 성분 가운데 HDL-C/TC의 비율은 유의적으로 증가하며 LDL-cholesterol (LDL-C)과 non-esterified fatty acid (NEFA)의 비율은 유의적으로 감소하여 혈중 유리지방산 농도를 감소시키며 혈중 콜레스테롤 상승을 억제시키고 혈당을 감소시키는 효과가 있는 것으로 평가되었다. 따라서 고려엉겅퀴 주정추출물이 함유된 인체적용시험시료(CNTM)는 체지방 개선에 우수한 효과가 있는 것으로 확인되었다.

• 생명과학회지
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• 제27권11호
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• pp.1357-1368
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• 2017

본 연구에서는 청국장의 항비만 및 항염증 효과를 알아보고자 C57BL/6 마우스에 고지방식이를 13주감 섭취시켜 비만을 유도한 후에 고지방 식이에 청국장을 10% 첨가하여 항비만과 항염증 활성을 확인하였다. 고지방식이를 통해 비만이 유도된 mice (HFD)에 고지방식이와 함께 청국장을 첨가하여 섭취한 그룹(CGJ)의 체중 증가율은 고지방식이군과 비교하였을 때 현저하게 감소하였을 뿐만 아니라 정상식이군보다도 유의적으로 감소하였으며 혈중 TG, TC, glucose, insulin, AST와 ALT 분비는 감소하였고 adiponectin의 수치는 유의적으로 증가하였다(p<0.05). 또한 H&E와 Oil red O staining을 통해 13주 동안 고지방식이를 통해 유도된 지방 간의 심각정도가 청국장의 섭취로 인하여 감소한 것을 확인하였다(p<0.05). 간세포는 대식세포, T세포와 같은 면역시스템의 세포들을 포함하고 있는데 비만으로 유도된 간 조직의 염증반응에 청국장이 미치는 영향을 조사하기 위해 FACS 분석을 수행하였다. CGJ군은 HFD군에 비하여 T cell의 침윤과 대식세포의 축적, 호중구의 유입이 유의적으로 감소하였다(p<0.05). 간 조직으로 침윤된 면역세포의 증가가 간 조직 내 염증반응을 유도하는지 확인하기 위해 염증성 cytokine의 수준을 조사한 결과 간과 지방 조직에서 염증성 cytokine인 MCP-1과 $TNF-{\alpha}$의 mRNA 발현이 감소하였으며 지방합성에 관여하는 $PPAR-{\gamma}$, SREBP-1와 $CEBP/{\alpha}$의 mRNA 발현 역시 감소하였다. 이러한 결과들을 통해 청국장이 면역 시스템과 지방생성 전사 인자들의 발현에 관여함으로써 adipogenesis를 조절함과 동시에 염증 억제 효과를 가진다는 사실을 증명하였다.

• Journal of Microbiology and Biotechnology
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• 제22권3호
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• pp.378-384
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• 2012

In aquatic invertebrates, particularly marine gastropods, organotin compounds induce irreversible sexual abnormality in females, which is termed imposex, at very low concentrations. Organotin compounds are agonists for nuclear receptors such as RXRs and $PPAR{\gamma}$. However, the imposex phenomenon has not been reported to act as an antagonist on estrogen receptors in other species, including vertebrates and invertebrates. In order to gain insights into the antagonistic activity of organotin compounds on estrogen receptors (ERs), we examined the inhibitive effect of these compounds on estradiol-dependent ${\beta}$-galactosidase activity using the yeast two-hybrid detection system consisting of a combination of the human estrogen receptor ($hER{\beta}$) ligand-binding domain and the co-activator steroid receptor co-activator-1 (SRC1). Tributyltin-hydroxide (TBT-OH) and triphenyltin-chlorine (TPT-Cl) exhibited an inhibitive effect on $E_2$-dependent transcriptional activity, similar to antagonistic chemicals such as 4-hydroxytamoxifen (OHT) or ICI 182,780, at a very low concentration of $10^{-14}$ M TBT or $10^{-10}$ M TPT, respectively. The yeast growth and transcriptional activity with transcriptional factor GAL4 did not exhibit any effect at the tested concentration of TBT or TPT. Moreover, the yeast two-hybrid system using the interaction between p53 and the T antigen of SV40 large did not describe any effect at the tested concentration of OHT or ICI 182,780. However, the interaction between p53 and T antigen was inhibited at a TBT or TPT concentration of $10^{-9}$ M, respectively. These results indicate that TBT and TPT act as inhibitors of ER-dependent reporter gene transcriptional activation and of the interaction between $hER{\beta}$ LBD and the co-activator SRC1 in the yeast two-hybrid system. Consequently, our data could partly explain the occurrence of organotin compound-induced imposex on the endocrine system of mammals, including humans.