• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 춘계학술발표회
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• pp.9-9
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• 2018

Arctii Fructus (AF), which contains arctigenin (ARC) as a major constituent, is traditionally used as an anti-inflammatory medicine to treat inflammatory sore throat. Although several studies have proven its anti-inflammatory effects, there have been no reports on its use in inflammation related disorders such as obesity, cancer metastasis, and allergic responses. This study investigated the anti-obesity effect and anti-metastasis effect of AF and ARC. AF and ARC inhibited weight gain by reducing the mass of white adipose tissue in high fat diet (HFD)-induced obese mice. Serum cholesterol levels were also improved by AF and ARC. In in vitro experiments, AF and ARC decreased differentiation of white adipocytes. Furthermore, AF induced differentiation of brown adipocytes, which are able to consume surplus energy through non-shivering thermogenesis. Also, AF and ARC inhibited colon cancer and lung metastasis of colon cancer. They suppressed not only colorectal cancer cell progression by inhibiting cell growth, but also prohibited lung metastasis by regulating epithelial-mesenchymal transition (EMT), migration, and the invasion. These effects were confirmed in an experimental metastasis mouse model. In addition, AF and ARC inhibited mast cell mediated allergic responses. Collectively, our study suggests that AF and ARC might show inhibitory effects on inflammation related diseases, including obesity, cancer, cancer metastasis, and allergic responses.

• Journal of Ginseng Research
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• 제41권3호
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• pp.347-352
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• 2017

Background: Panax ginseng (PG) has a long history of use in Asian medicine because of its multiple pharmacological activities. It has been considered that PG in a type of white ginseng may induce undesirable thermogenic effects, but not in a type of red ginseng. However, there is a lack of evidence about the correlation between ginsenoside and thermogenesis. Methods: We investigated the effects of PG with different ginsenoside compositions on body temperature, blood pressure, and thermogenesis-related factors in rats. Results: With increasing steaming time (0 h, 3 h, 6 h, and 9 h), the production of protopanaxadiol ginsenosides increased, whereas protopanaxatriol ginsenosides decreased in white ginseng. In both short- and long-term studies, administration of four ginseng extracts prepared at different steaming times did not induce significant changes in body temperature (skin, tail, and rectum) and blood pressure of rats compared to saline control. In addition, there were no significant differences in the molecular markers related to thermogenesis (p > 0.05), mRNA expressions of peroxisome proliferator-activated receptor-gamma coactivator-$1{\alpha}$ and uncoupling protein 1 in brown adipose tissue, as well as the serum levels of interleukin-6, inducible nitric oxide synthase, and nitrite among the treatment groups. Conclusion: These observations indicate that the potential undesirable effects of PG on body temperature could not be explained by the difference in ginsenoside composition.

• 한국해양생명과학회지
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• 제8권2호
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• pp.186-189
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• 2023

Uncoupling protein 1 (UCP1) is a unique mitochondrial membranous protein expressed in brown adipose tissue (BAT) in mammals. While its expression in response to cold temperatures and adipogenic inducers is well-characterized in mammals and human infants, the molecular characterization and expression of UCP1 in fish remain unexplored. To address this gap, we analyzed UCP1 expression in response to adipogenic inducers in a fish cell line, rainbow trout gonadal cells (RTG-2), and compared it with UCP1 expression in three mammalian preadipocytes, 3T3-L1, T37i, and WT1 exposed to the Peroxisome proliferator-activated receptor gamma (PPARγ) agonists, rosiglitazone (Rosi). In mammalian preadipocytes, UCP1 protein was highly expressed by Rosi, with an induction of adipogenesis observed in a time-dependent manner. This suggests that UCP1 plays a significant role in adipogenesis in mammals. However, RTG-2 cells showed no response to adipogenic inducers and exhibited only marginal expressions of UCP1. These results imply that RTG-2 cells may lack crucial responsive mechanisms to adipogenic signals or that the adipogenic response is regulated by other mechanisms. Further studies are needed to confirm these phenomena in fish preadipocytes when an appropriate cell line is established in future research.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.186-196
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• 2023

Dyglomera^® is an aqueous ethanol extract derived from the fruit and pods of Dichrostachys glomerata. A previous study has revealed that Dyglomera regulates adipogenesis and lipolysis by modulating AMP-activated protein kinase (AMPK) phosphorylation and increased expression levels of lipolysis-related proteins in white adipose tissue of high fat diet-induced mice and 3T3-L1 adipocyte cells. To further investigate mechanisms of Dyglomera, additional studies were performed using 3T3-L1 cells. Results revealed that Dyglomera downregulated adipogenesis by inhibiting the protein kinase B/mammalian target of rapamycin signaling pathway and reconfirmed that it downregulated gene expression levels of proliferator-activated receptor (PPAR)-γ, CCAAT enhancer binding protein α, sterol-regulation element-binding protein-1c. Dyglomera also reduced adipokines such as tumor necrosis factor alpha, interleukin-1β, and interleukin 6 by regulating leptin expression. Moreover, Dyglomera promoted beige-and-brown adipocyte-related phenotypes and regulated metabolism by increasing mitochondrial number and expression levels of genes such as T-box protein 1, transmembrane protein 26, PR domain 16, and cluster of differentiation 40 as well as thermogenic factors such as uncoupling protein 1, proliferator-activated receptor-gamma co-activator-1α, Sirtuin 1, and PPARα through AMPK activation. Thus, Dyglomera not only can inhibit adipogenesis, but also can promote lipolysis and thermogenesis and regulate metabolism by affecting adipokine secretion from 3T3-L1 adipocytes.

• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.181-188
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• 2021

Bacillus subtilis and Enterococcus faecium are commonly used probiotics. This study aimed to identify the effect of live combined Bacillus subtilis R0179 and Enterococcus faecium R0026 (LCBE) on obesity-associated hyperlipidemia and gut microbiota in C57BL/6 mice. Forty male C57BL/6 mice were divided into four groups: normal group (N group), model group (M group), low-dose group (L group), and high-dose group (H group). Mice were gavaged with LCBE at 0.023 g/mice/day (L group) or 0.23 g/mice/day (H group) and fed with a high-fat diet for 8 weeks. In vitro E. faecium R0026 showed an ability to lower the low-concentration of cholesterol by 46%, and the ability to lower the high-concentration of cholesterol by 58%. LCBE significantly reduced the body weight gain, Lee index, brown fat index and body mass index of mice on a high-fat diet. Moreover, LCBE markedly improved serum lipids (including serum triglyceride, total cholesterol, low-density lipoprotein and high-density lipoprotein) while also significantly reducing liver total cholesterol. Serum lipopolysaccharide and total bile acid in L and H groups decreased significantly compared with M group. PCR-DGGE analysis showed that the composition of gut microbiota in the treatment groups was improved. Akkermansia muciniphila was found in H group. The PCA result indicated a similar gut microbiota structure between LCBE treatment groups and normal group while the number of bands and Shannon diversity index increased significantly in the LCBE treatment groups. Finally, qPCR showed Bifidobacterium spp. increased significantly in H group compared with M group, LCBE alleviated liver steatosis and improved brown adipose tissue index.

• Journal of Microbiology and Biotechnology
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• 제34권8호
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• pp.1688-1697
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• 2024

The current study aimed to determine whether Strongylocentrotus intermedius (S. intermedius) extract (SIE) exerts anti-obesity potentials employing 3T3-L1 cells as in vitro model. Herein we reported that treatment of SIE for 6 days reduced lipid accretion and triglyceride content whereas it increased the release of free glycerol. The inhibited lipid accumulation and induced lipolysis were evidenced by the downregulation of lipogenesis proteins, such as fatty acid synthase and lipoprotein lipase, and the upregulation of hormone-sensitive lipase expression. Furthermore, the downregulation of adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein α, and sterol regulatory element-binding protein 1, highlights that reduced lipid accumulation is supported by lowering adipocyte differentiation. Additionally, treatment activates brown adipocyte phenotype in 3T3-L1 cells by inducing expression of brown adipose tissue-specific proteins, such as uncoupling protein 1 and peroxisome proliferator-activated receptor-γ coactivator 1α. Moreover, SIE induced the phosphorylation of AMP-activated protein kinase (AMPK). The pharmacological approach using AMPK inhibitor revealed that the restraining effect of SIE on adipogenesis and promotion of adipocyte browning were blocked. In GC-MS analysis, SIE was mainly composed of cholest-5-en-3-ol (36.71%) along with saturated and unsaturated fatty acids which have favorable anti-obesity potentials. These results reveal that SIE has the possibility as a lipid-lowering agent for the intervention of obesity.

• 대한한방부인과학회지
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• 제25권3호
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• pp.40-60
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• 2012

Objectives: The object of this study was to observe antitumor, anticachexia and immunomodulatory effects of Shipyeukmiyeugi-eum(SYM) on human breast cancer cell, MCF-7, xenograft Balb/c nu-nu nude mice. Methods: Three different dosages of SYM-125, 250 and 500 mg/kg were orally administered once a day for 28 days from 11 days after tumor cell inoculation, and the changes on the body weights, tumor volume and weights, weights of spleen and popliteal lymph node and epididymal fat, serum IL-6 and IFN-${\gamma}$ levels, NK cell and peritoneal macrophage activities, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents were observed. In addition, histopathological observations of apoptotic cell, spleen, popliteal lymph node and cervical brown adipose were also detected. The results were compared with a potent cytotoxic estrogen receptor antagonist, Tamoxifen 20 mg/kg treated mice. Results: Tumor volumes and weights were decreased without cytotoxic effects on the both MCF-7 and MCF-10A cells as results of all three different dosages of SYM treatment. And weights of body, spleen, popliteal lymph node, epididymal fat, serum IFN-${\gamma}$, NK cell, peritoneal macrophage activities, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents were increased with decrease of serum IL-6. At histopathological observations, apoptotic tumor cells, spleen, popliteal lymph node and cervical brown adipose tissue were increased. That means tumor-related immunosuppress and cachexia were markedly inhibited by SYM treatment as compared with tumor-bearing mice. On the other hand, Tamoxifen showed marked cytotoxic effects against MCF-7 and MCF-10A, decreases of tumor volume and weights, and increases of apoptotic tumor cells and related decreases of tumor cell volumes, but tamoxifen markedly deteriorated the tumor-related immune-suppress and cachexia. Conclusions: The results obtained in this study suggest that SYM showed favorable anticancer effects and anticachexic effects on the MCF-7 cell xenograft through immunomodulatory effects. SYM did not induce any cytotoxic effects against both normal and cancer cells.

• 한국식품영양과학회지
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• 제31권5호
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• pp.788-795
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• 2002

본 연구는 프락토즈 중합체인 레반의 지질 감소 효과와 비만 유전자인 UCP를 통한 에너지 대사에 미치는 효과를 살펴보기 위하여 성장기 6주간 AIN-76A diet로 사육한 흰쥐에게 레반을 식이 섭취량의 1%, 2%로 5주간 경구투여하여, 혈중 지질 수준과 체지방 형성 및 혈중 인슬린, 렙틴 농도와 갈색 지방 조직, 백색지방 조직, 골격 근육, 시상하부에서 의 UCP mRNA 발현량 변화를 관찰하였다. 연구 결과를 종합해 보면 다음과 같다. 1) 레반군에서 혈청 중성지방과 총 콜레스테롤은 감소하고 HDL 콜레스테롤 수준은 영향을 미치지 않아 1%와 2% 레반 공급이 지질 대사를 개선시킬 수 있음을 보여주었다. 2) 1%와 2% 레반군에서 내장 지방 무게가 감소하여 적은 양의 레반 공급으로 체지방 축적이 억제될 수 있음을 보여주었다. 3) 갈색 지방 조직과 부고환 지방, 복막 지방 무게는 그룹간 차이가 나타나지 않았다. 4) 혈청 인슬린 농도는 1% 레반군에서, 혈청 렙틴 농도는 1% 레반군, 2% 레반군에서 대조군에 비해 감소하는 경향을 나타내었으나 통계적 유의성은 나타나지 않았다. 5) 1%와 2% 레반 공급에 의하여 갈색 지방 조직과 골격근육, 시상하부에서의 UCP mRNA발현량에는 변화가 없었다. 6) 백색 지방 조직의 UCP 2 mRNA 발현량이 레반 공급에 의해 증가하여 1%와 2%레반 공급에 의해 에너지 소비율이 증가할 수 있음이 나타났다 결론적으로 저농도의 1%와 1% 액상 레반 공급은 총 식이의 ,3%～5% 레반 공급과 비교하여 혈중 총 콜레스테롤과 중성 지방 감소 효과에는 차이가 있으나 UCP 발현 증가에 미치는 영향은 적은 것으로 보인다. 그러나 저농도의 1～2% 액상 레반 공급으로 지질 대사를 개선하고 체지방 축적을 어느 정도 억제하는 효과를 나타냄을 알 수 있으며 이에 관한 임상 연구로 레반의 고지혈증과 비만을 조절하는 기능성 식품 소재로서의 가능성 검색이 요망된다.

• 생명과학회지
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• 제29권3호
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• pp.303-310
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• 2019

비만은 체내 과도한 지방 축적으로 인하여 지방세포 자체에서 염증성 사이토카인이 증가로 인하여 세포의 기능을 약화시킨다. 규칙적인 운동은 지방분해와 갈색지방 증가로 인해 비만의 치료방법 중 핵심 전략으로 적용되고 있다. 고강도 운동은 염증성 사이토카인과 근형질세망 스트레스 발생을 초래하여 지방대사에 부정적인 결과를 초래하는 것으로 알려져 있다. 그러나 비만모델에서 중강도 운동과 고강도 운동에 의한 인플라마좀, 대식세포 침윤, 갈색지방 관련 바이오 마커의 비교연구는 이루어진 바 없다. 따라서 이 연구의 목적은 중강도 유산소 운동과 고강도 운동을 비교하여 인플라마좀(NLRP3, ASC), 대식세포 침윤인자 M1 (CD11c, CD86), M2 (CD206), 갈색지방($PGC1{\alpha}$, BMP7, PRDM, UCP1) 관련 변인에 우선적인 효과가 있는지 비교분석하고자 하였다. 이 연구의 목적을 위해 1) 정상식이 그룹(normal diet control, NC; n=10), 2) 60% 고지방식이 그룹(high-fat diet control, HC; n=10), 3) 중강도 운동 그룹(high fat diet with moderate intensity exercise, HME; n=10), 4) 고강도 운동그룹(high fat diet with high intensity exercise, HIE; n=10)으로 나누어 실시하였다. 중강도 운동 그룹은 고지방식이 그룹과 비교하여 NLRP3, F480, CD11c, CD8의 발현이 유의하게 낮아졌다. 중강도 운동은 CD206, $PGC1{\alpha}$, BMP7, PRDM이 유의하게 증가하였다. 고강도 운동은 NLRP3, CD11c and CD86은 유의하게 감소한것으로 확인되었다. 그러나 고강도 운동은 $PGC1{\alpha}$, BMP7는 증가한다. 이러한 결과는 중강도 운동은 인플라마좀, 대식세포 M1, M2 침윤과 갈색지방 세포 관련 요인의 개선이 효과적인 것으로 나타났다.

• 한국자원식물학회지
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• 제29권4호
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• pp.355-362
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• 2016

혈중 LDL 콜레스테롤 농도는 이상 lipoprotein metabolism의 유효한 지표로 간주되고 있으며, 관상동맥질환 및 동맥경화증의 위해성과 직접 연관이 있는 것으로 알려져 있다(Goldstein and Brown, 1983; Venter et al., 1990). 또한 HDL 콜레스테롤은 말초조직에서 간으로의 콜레스테롤의 이동에서 중요한 역할을 하며, 유리형 콜레스테롤의 에스테르화를 촉매하는 효소인 lecithin:cholesterol acetyltransferase (LCAT)를 활성화하여 세포 안으로 콜레스테롤의 유입을 억제함으로써 동맥경화를 막는 역할을 한다(Steinberg and Witztum, 1990). 본 연구 결과 석창포 열수 추출물은 혈중 triglyceride 수준을 유의하게 낮추는 효과가 입증되었다. 또한 석창포 열수 추출물은 혈중 total cholesterol과 HDL-cholesterol 수준을 WKAG-M, WKAG-H군에서 유의하게 감소 시켰으며 LDL-cholesterol 수준은 석창포 열수 추출물 투여에 의해 유의적으로 증가되었다. 또한 이러한 결과로부터 석창포 열수 추출물은 혈중 지질 조절에 의해 동맥 경화 지수를 감소시킬 수 있으며 심장 위험 지수 또한 감소시킬 수 있음을 알 수 있었다. 추후 석창포 열수 추출물 분획 중의 각 성분들이 혈중 지질 성상에 미치는 효과를 규명하는 연구를 수행하여 유효성분에 대한 연구를 계속할 예정이다.