• 한국미생물·생명공학회지
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• 제40권1호
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• pp.50-56
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• 2012

Wnt/${\beta}$-catenin 신호전달체계는 세포의 분화와 증식, 기관의 발생과 조절을 담당하는 중요한 세포내 신호전달체계이다. 발생과정에서 Wnt/${\beta}$-catenin 신호전달체계의 작용이 지방세포로의 분화를 억제하고 조골세포와 신경세포로의 분화는 촉진한다는 많은 연구들이 보고되어 있으며, 현재 Wnt/${\beta}$-catenin 신호전달체계의 조절을 통한 여러 질병의 치료와 예방에 대한 관심이 대두되고 있다. 본 연구에서는 세포를 기반으로 한 초고속 저분자 스크리닝 시스템을 이용하여 Wnt의 상승제인 silybin을 발굴하였다. silybin은 Wnt가 존재 않을 경우에는 ${\beta}$-catenin 단백질의 수준에 영향을 미치지 않지만 Wnt가 존재할 경우, mRNA 발현양의 변화 없이 세포질내의 ${\beta}$-catenin 단백질의 수준을 증가시킨다. 또한 silybin에 의해 증가된 ${\beta}$-catenin으로 인해 지방세포분화에 중요한 전사인자라고 알려진 PPAR-${\gamma}$와 C/EBP-${\alpha}$의 발현을 억제한다. 따라서 이 연구에서는 silybin이 세포질내 ${\beta}$-catenin 단백질의 수준을 증가시킴으로써 Wnt/${\beta}$-catenin 신호전달체계를 활성한다는 사실을 제시하였다.

• 생명과학회지
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• 제24권7호
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• pp.777-783
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• 2014

항암제로 알려진 cisplatin과 t-BHP를 토끼에 투여하여 유도된 급성 신부전 시 산조인 추출액을 처리하였을 때 신장 세포의 보호에 미치는 항산화 효과를 조사하였다. 신장을 분리한 후 신피질 절편 실험에서 세포의 손상을 유발하는 지질과산화 및 LDH 실험에서 t-BHP 단독 처리 시 대조군에 비하여 각각 3배, 5배 이상 증가하였으나 산조인 추출액 0.5%를 동시 처리하였을 때는 대조군 수준으로 감소하였다. Creatinine 측정과 지질과산화 실험에서 cisplatin $5mg{\cdot}kg^{-1}$을 복강 투여한 군의 creatinine 농도가 $2.13{\pm}0.1mg{\cdot}dl^{-1}$로 나타났으나 산조인 추출액 $50mg{\cdot}kg^{-1}{\cdot}day^{-1}$을 7일간 전처리 후 cisplatin 투여 48시간 경과한 군은 $0.84{\pm}0.1mg{\cdot}dl^{-1}$로 creatinine의 농도가 약 60% 감소되는 신장보호 효과를 나타내었고, 지질과산화 검사는 cisplatin 단독 투여 시 대조군에 비하여 1.6배 높게 나타났으나 산조인 추출액 전처리 시 1.1배로 대조군과 유사하였다. 병리조직 검사는 cisplatin 단독 처리군에서 근위곱슬세관이 대조군에 대하여 더 붉게 염색되었으며 근위곱슬세관은 내강의 융모세포가 탈락하여 공포를 형성하였다. 그러나 산조인 추출액을 7일간 전처리한 군에서는 근위곱슬세관이 대조군과 유사한 염색소견을 보였고 근위곱습세관도 내강의 융모세포 탈락이 거의 나타나지 않았다. 따라서 cisplatin과 t-BHP에 의해 유발된 신장세포 손상에 대하여 산조인 추출액이 항산화 효과를 보였다.

• 한방비만학회지
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• 제11권1호
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• pp.47-60
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• 2011

Objectives The objective of this study was to contribute to the development of pharmacupuncture for obesity treatment by reviewing the studies of pharmacupuncture experimentations and clinical trials. Methods We searched the papers with keywords of 'obesity' and 'pharmacupuncture' in the search site, RISS, Oriental medicine advanced searching integrated system(OASIS), Korean traditional knowledge portal, the society of Korean medicine for obesity research, Korean pharmacupuncture institute, the Korean academy of oriental rehabitation medicine and Korean acupuncture & moxibustion society. Results 1. We reviewed 37 articles searched. 27 articles(73.0%) were animal experimentations, 5 articles(13.5%) were cell experimentations, 4 articles(10.8%) were clinical trials and 1 article(2.7%) was study analysis. 2. The herbs, using for animal experimentations, were atratylodes japonica, coix lachrymajobi, ephedra sinica, crataegus pinnatifida, wild ginseng and etc. Acupucture points were joksamni(ST36), zhongwan(CV12), gansoo(BL18), pungnyung(ST40), umnungchon(SP9), bisu(BL20), gokji (LI11), cheun-chu(ST25) and etc. 3. For cell experimentations, preadipocytes and adipocytes performed on cell cultures with using rats, 3T3-L1 preadipocytes and porcine skin including fat tissue were treated with fel ursi, bovis calculus, ephedrae herba, spirodelae herba, wild ginseng. 4. For clinical trials, Sangsik no.1, Bigiheo, ephedra, green tea and sweet bee venom were injected at the region where a lot of fat like zhongwan(CV12), xiawan(CV10), kwanwon(CV4), cheun-chu(ST25) and thigh. Conclusion Through animal and cell experimentations and clinical trials, the treatment of obesity using local acupuncture therapy was effective. For clinical use, however, it is considered that animal and cell experimentation and clinical trial's connection using one kind of herb and studies about more clinical trials and associated side effects are needed.

• 한방재활의학과학회지
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• 제24권3호
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• pp.11-27
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• 2014

Objectives This study was designed to evaluate the effects of Ephedra Sinica and Fibrosum Gypsum extract on obesity by using 3T3-L1 cells and high fat diet rats. Methods In vitro, Ephedra Sinica and Fibrosum Gypsum extract (50, 100, 200, $500{\mu}g/ml$) were added in 3T3-L1 cells. Cytotoxicity was measured by MTT assasy. Adipocyte differentiation was measured by Oil Red O staining, GPDH activity and $C/EBP{\alpha}$ protein expression. In vivo, Sprague-Dawley rats were divided into 5 groups : Normal diet group (Normal group), taken high fat diet and no treatment group (Control group), taken high fat diet and orally administered Ephedra Sinica and Fibrosum Gypsum extract daily (Group I: 50 mg/kg, Group II: 100 mg/kg, Group III : 200 mg/kg, oral). For 6 weeks of administration, body weight and the amount of food intake were measured once a week. After administration, blood analysis (AST, ALT, T-Bilirubin, BUN, RBC, Hb, HCT), serum lipid level (triglyceride, Total cholesterol, HDL, LDL), serum leptin level, epididymal adipose tissue weight and histological finding of liver were estimated. Results In vitro, The cytotoxicity was not significant. 3T3-L1 cell's differentiation was significantly decreased in Oil Red O staining, GPDH activity and $C/EBP{\alpha}$ protein expression. In vivo, Body weight and the amount of food intake, AST, ALT, Total cholesterol, TG, LDL, serum leptin, epididymal adipose tissue weight showed significant decrease in group I, group II and group III. There were no significant difference in T-bilirubin, BUN, RBC, Hb and HCT between all groups. HDL showed significant increase in group I, group II and group III. In histological finding of liver tissue, there were decreased adiposity and cytopathic effect in group I, group II and group III. Conclusions It is suggested that Ephedra Sinica and Fibrosum Gypsum extract can be used in the treatment of obesity.

• 한국식품영양과학회지
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• 제44권3호
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• pp.314-323
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• 2015

본 연구는 구중구포법 과정의 흑삼 1~9포를 대상으로 열수 및 70% 에탄올 추출물의 ginsenosides을 분석한 결과 생리 활성이 높다고 판단한 흑삼 5포와 9포 열수 및 에탄올 추출물을 각각 3T3-L1 지방세포, RAW264.7 대식세포, 지방유래 줄기세포에 처치하여 세포독성, 지질축적(adipogenesis) 및 염증인자 변화를 관찰하였다. 본 연구에서는 열수 추출물보다 에탄올 추출물 흑삼에서 효율적으로 ginsenosides가 추출되었다. 또한 흑삼 에탄올 추출물이 $PPAR{\gamma}$ 및 C/$EBP{\alpha}$ 감소, AMPK의 인산화 증가 등 adipogenesis 관련인자를 억제하였으며, 아울러 염증성 사이토카인의 분비를 억제하였다. 따라서 비만 및 대사성 질환의 예방에도 잠정적으로 이용될 수 있을 것으로 기대되지만 ginsenosides와 비만과의 조절기전 연구 및 항염증성 기전 등에 대한 정확한 기전 규명이 필요하다. 현재 인삼에 함유된 ginsenosides를 이용하여 체지방 감소 등의 기능성식품으로 많이 개발되고 있는 현실을 감안해 볼 때 홍삼 및 흑삼의 제조 기술인 구증구포법의 효율적인 표준화 공정기술, 유효 생리활성 성분의 대량 생산 및 안전성 기술 등이 개발된다면 항비만에 대한 고부가 가치 상품개발이 가능할 것으로 기대된다.

• 한국식품영양과학회지
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• 제46권3호
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• pp.279-288
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• 2017

본 연구에서는 발효콩 유지가 비만 억제 및 예방, 3T3-L1 지방전구세포의 성장 및 분화 억제 효과를 관찰하기 위해 실험을 실시하였다. 3T3-L1 지방전구세포에 발효콩 유지를 처리하여 세포생존율을 측정한 결과, NF군 $100{\mu}g/mL$에서 3T3-L1 지방전구세포의 생존율을 유의적으로 감소시켜 세포독성이 나타났다. 분화를 유도한 다음 세포 내 triglyceride 함량을 측정한 결과, 비발효콩 유지(NF) 처리군보다 발효콩 유지처리군에서 triglyceride 함량 저해 효과가 높게 나타났으며, 특히 BS, LBA, BLO군 순으로 높게 나타났다. 또한, BS군, LBA군, BLO군 순으로 지방세포분화 관련 유전자인 $PPAR{\gamma}$의 mRNA 발현을 농도 의존적으로 감소시켰으며, $PPAR{\gamma}$ 유전자와 상관관계에 있는 $C/EBP{\alpha}$ 유전자도 농도 의존적으로 감소시켰다. 그리고 adiponectin 유전자의 발현은 농도 의존적으로 증가시켰다. 고지방식이로 비만을 유도한 C57BL/6J 생쥐를 이용하여 항비만 활성을 관찰한 결과, 총 체중증가량은 대조군에 비해 4주째에 감소하는 경향이 나타났다. 혈액 내 지질농도를 측정한 결과 중성지방, 총콜레스테롤, LDL-콜레스테롤 함량은 LBA, BLO군에서 유의적으로 낮게 나타났으며(P<0.05), HDL-콜레스테롤 함량은 대조군보다 증가하였으나 유의적인 차이는 나타나지 않았다. 동맥경화 지수인 AI(atherogenic index)는 대조군보다 감소시키는 경향을 보였다. 비만관련 호르몬인 adiponectin의 농도는 SO, BS, LBA, BLO군에서 유의적으로 증가하였고(P<0.05), insulin 농도는 유의적으로 감소하였다(P<0.05). Leptin은 대조군보다 감소하였으나 유의적인 차이는 나타나지 않았다. 따라서 이러한 결과를 종합하여 볼 때 발효콩 유지가 3T3-L1 지방전구세포의 mRNA 단계에서부터 지방분화를 억제하여 항비만 활성을 가지고 있는 것으로 추정되고, 고지방식이로 비만이 유도된 C57BL/6J 생쥐에서 총체중을 감소시키고, 혈액 내 지질농도인 triglyceride와 총콜레스테롤, LDL-콜레스테롤 및 HDL-콜레스테롤과 비만관련 호르몬인 adiponectin, insulin, leptin을 조절하여 항비만 활성을 가지고 있는 것으로 확인되었다. 이 결과로 발효콩 유지가 항비만 생리활성을 나타내는 새로운 식품 소재로서 이를 활용한 기능성 식품 개발의 가능성이 있다고 생각된다.

• Molecules and Cells
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• 제45권12호
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• pp.963-975
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• 2022

Exogenous polyamines are able to induce life span and improve glucose homeostasis and insulin sensitivity. However, the effects of exogenous polyamines on adipocyte differentiation and which polyamine transporters mediate them have not been elucidated yet. Here, we identified for the first time that exogenous polyamines can clearly stimulate adipocyte differentiation through polyamine transporters, solute carrier family 3 member A2 (SLC3A2) and SLC7A1. Exogenous polyamines markedly promote 3T3-L1 adipocyte differentiation by increasing the intracellular lipid accumulation and the expression of both adipogenic and lipogenic genes in a concentration-dependent manner. In particular, exogenous putrescine mainly regulates adipocyte differentiation in the early and intermediate stages. Moreover, we have assessed the expression of polyamine transporter genes in 3T3-L1 preadipocytes and adipocytes. Interestingly, the putrescine-induced adipocyte differentiation was found to be significantly suppressed in response to a treatment with a polyamine transporter inhibitor (AMXT-1501). Furthermore, knockdown experiments using siRNA that specifically targeted SLC3A2 or SLC7A2, revealed that both SLC3A2 and SLC7A2 act as important transporters in the cellular importing of exogenous putrescine. Thus, the exogenous putrescine entering the adipocytes via cellular transporters is involved in adipogenesis through a modulation of both the mitotic clonal expansion and the expression of master transcription factors. Taken together, these results suggest that exogenous polyamines (such as putrescine) entering the adipocytes through polyamine transporters, can stimulate adipogenesis.

• International Journal of Oral Biology
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• 제37권1호
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• pp.31-36
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• 2012

Dlx3 and Dlx5 are homeobox domain proteins and are well-known regulators of osteoblastic differentiation. Since possible reciprocal relationships between osteogenic and adipogenic differentiation in mesenchymal stem cells exist, we examined the regulatory role of Dlx3 and Dlx5 on adipogenic differentiation using human dental pulp stem cells. Over-expression of Dlx3 and Dlx5 stimulated osteogenic differentiation but inhibited adipogenic differentiation of human dental pulp stem cells. Dlx3 and Dlx5 suppressed the expression of adipogenic marker genes such as $C/EBP{\alpha}$, $PPAR{\gamma}$, aP2 and lipoprotein lipase. Adipogenic stimuli suppressed the mRNA levels of Dlx3 and Dlx5, whereas osteogenic stimuli enhanced the expression of Dlx3 and Dlx5 in 3T3-L1 preadipocytes. These results suggest that Dlx3 and Dlx5 exert a stimulatory effect on osteogenic differentiation of stem cells through the inhibition of adipogenic differentiation as well as direct stimulation.

• Journal of Microbiology and Biotechnology
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• 제34권3호
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• pp.634-643
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• 2024

Juglans mandshurica Maxim. walnut (JMW) is well-known for the treatment of dermatosis, cancer, gastritis, diarrhea, and leukorrhea in Korea. However, the molecular mechanism underlying its antiobesity activity remains unknown. In the current study, we aimed to determine whether JMW can influence adipogenesis in 3T3-L1 preadipocytes and high-fat diet rats and determine the antioxidant activity. The 20% ethanol extract of JMW (JMWE) had a total polyphenol content of 133.33 ± 2.60 mg GAE/g. Considering the antioxidant capacity, the ABTS and DPPH values of 200 ㎍/ml of JMWE were 95.69 ± 0.94 and 79.38 ± 1.55%, respectively. To assess the anti-obesity activity of JMWE, we analyzed the cell viability, fat accumulation, and adipogenesis-related factors, including CCAAT-enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein-1c (SREBP1c), peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). We found that total lipid accumulation and triglyceride levels were reduced, and the fat accumulation rate decreased in a dose-dependent manner. Furthermore, JMWE suppressed adipogenesis-related factors C/EBPα, PPARγ, and SREBP1c, as well as FAS and ACC, both related to lipogenesis. Moreover, animal experiments revealed that JMWE could be employed to prevent and treat obesity-related diseases. Hence, JMWE could be developed as a healthy functional food and further explored as an anti-obesity drug.

• 대한본초학회지
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• 제30권4호
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• pp.21-27
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• 2015

Objectives : In this study, we investigated the biological activities such as anti-obesity using Samwondan ethanol extract (SWD). SWD is a complex with Salicornia herbacea Linnaeus, Saururus chinensis Baill and Houttuynia cordata Thunberg as the main raw material.Methods : The SWD was extracted 80% ethanol. 3T3-L1 preadipocytes were induced adipogenesis by differentiation media with SWD at 1 μg/mL, 10 μg/mL, and 100 μg/mL. Effect of SWD performed using MTT assay, oil red O staining (observation by microscope), and reverse transcription polymerase chain reaction. Also we measured production of triglyceride (TG), fatty acid, and acetyl-CoA carboxylase (ACC).Results : Non-cytotoxicity was in all test group from range of 1 μg/mL to 100 μg/mL on pre-adipocyte. The droplet and production of lipid were decreased significantly by the SWD. And TG was decreased by approximately 89%, 85% and 82%, upon the SWD treatment at concentration of 1 μg/mL, 10 μg/mL, and 100 μg/mL. Moreover, the SWD showed inhibitory effects on the expression of the C/EBP (CCAAT/enhaner binding protein)β, C/EBPα, and peroxisome proliferator-activated receptorγgenes in adipocytes. The SWD at 100 μg/mL concentration showed inhibitory effect on fatty acid production by 79%. Also ACC production were decreased dose-dependently.Conclusions : From the results above, we concluded that the SWD indicated significantly anti-obesity effects.