• Toxicological Research
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• 제30권1호
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• pp.19-25
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• 2014

Licochalcone (LC), a major phenolic retrochalcone from licorice, has anti-inflammatory activity. This study investigated the effects of licochalcone A (LCA) and licochalcone E (LCE) on Liver X receptor-${\alpha}$ ($LXR{\alpha}$)-mediated lipogenic gene expression and the molecular mechanisms underlying those effects. LCA and LCE antagonized the ability of $LXR{\alpha}$ agonists (T0901317 or GW3965) to increase sterol regulatory element binding protein-1c (SREBP-1c) expression and thereby inhibited target gene expression (e.g., FAS and ACC) in HepG2 cells. Moreover, treatment with LCA and LCE impaired $LXR{\alpha}/RXR{\alpha}$-induced CYP7A1-LXRE-luciferase (CYP7A1) transactivation. The AMPK-Sirt1 signaling pathway is an important regulator of energy metabolism and, therefore, a potential therapeutic target for metabolic diseases, including hepatic steatosis. We found here that LCE increased AMPK phosphorylation and Sirt1 expression. We conclude that LC inhibits SREBP-1c-mediated hepatic lipogenesis via activation of the AMPK/Sirt1 signaling pathway.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2023년도 임시총회 및 춘계학술대회
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• pp.55-55
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• 2023

With the COVID-19 pandemic, there is increasing interest in anti-obesity strategies. According to the National Statistical Office, the obesity rate in Korea was 38.3% in 2020 and 37.1% in 2021. Obesity is a risk factor for several severe diseases, including stroke, heart disease, type 2 diabetes, and certain types of cancer. Pinus rigida × Pinus taeda is a hybrid of Pinus rigida Mill and Pinus taeda Linn, and its cones are considered a by-product. Although previous studies have investigated their pharmacological effects on antioxidant activity and protection against oxidative DNA damage, few researchers have explored their potential as functional natural materials. Therefore, we evaluated the anti-obesity effects of the cone of ethyl acetate fraction of P. rigida × P. taeda (ERT), specifically its ability to inhibit lipid accumulation. Our analysis showed that ERT contains phytochemicals (catechin and caffeic acid) which are known to improve immune function and inhibit cell damage. ERT inhibited lipid droplet accumulation at the cellular levels through Oil Red O staining. Furthermore, ERT suppressed the expression of adipogenic transcription factors (PPARγ and CEBP/α) as well as downstream lipogenic target genes (FAS and SREBP-1) thereby inhibiting adipogenesis. ERT also down-regulated key adipogenic markers, including aP2α, while inducing the phosphorylation of AMPK. It has been reported that PPARγ and CEBP/α are expressed in the early stages of adipose differentiation, while SREBP-1 is expressed in the late stage. Therefore, our findings suggest that ERT activates AMPK signaling pathways, which inhibits adipogenic transcription factors (PPARγ, C/EBPα, and SREBP1) and lipogenic genes (FAS and aP2α), thereby blocking lipid accumulation and preventing obesity and related disorders. ERT showed potential as a new resource for developing a functional material for anti-obesity agents.

• Fisheries and Aquatic Sciences
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• 제27권2호
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• pp.122-135
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• 2024

Obesity is a disease involving mechanisms of fat accumulation, low-grade inflammatory cytokine release, and mitochondrial dysfunction. The aim of the current study was to investigate the effects of abalone intestine extract on fat metabolism in 3T3-L1 adipocytes and high fat diet-induced zebrafish larvae. The total phenol content was highest in subcritical water extract at 210℃ (SW210) among hot water, ethanol, and subcritical water extracts of abalone intestine. In addition, SW210 of male abalone intestine (MASW210) most effectively controlled the lipid accumulation and expression of adipogenic or lipogenic regulators (PPAR-γ, C/EBPα, SREBP-1c, and FAS) in 3T3-L1 adipocytes. Likewise, in zebrafish larvae fed high fat, MASW210 significantly suppressed body weight, glucose levels, and lipid accumulation. The mRNA expression related to adipogenesis (PPAR-γ and C/EBPα), lipogenesis (SREBP-1c and FAS), inflammatory cytokines (TNF-α and IL-6), energy m/;.etabolism (AMPK, lepr, SIRT1, and adiponectin), and mitochondrial biogenesis (PGC-1α and CPT-1) were significantly regulated by treatment with MASW210. These results suggest that abalone intestine extract such as MASW210, are useful biomaterials for improving obesity and metabolic diseases.

• 한방재활의학과학회지
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• 제32권2호
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• pp.19-36
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• 2022

Objectives This study is to investigate the effects and mechanisms of Imyo-san (IMS) on the obese mice model induced by high-fat diet. Methods Antioxidative capacity was measured by in vitro method. C57BL/6 mice were randomly assigned into 5 groups (n=7). Normal group was fed general diet (Normal). The other 4 groups were fed high fat diet (HFD) with water (Control), with Garcinia gummi-gutta (GG, Garcinia gummi-gutta 200 mg/kg), with low-dose IMS (IMSL, Imyo-san 0.54 g/kg) and with high-dose IMS (IMSH, Imyo-san 1.08 g/kg). Results IMS showed high radical scavenging activity. After 6 week experiment, body weight, food intake, food efficiency ratio (FER), epididymal fat and liver weight, triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, sterol regulatory element-binding protein-1 (SREBP-1), phospho-acetyl-CoA carboxylase (p-ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), SREBP-2, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), phospho-liver kinase B1 (p-LKB1), phospho-AMP-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor 𝛼 (PPAR𝛼), peroxisome proliferator-activated receptor 𝛾 coactivator-1𝛼 (PGC-1𝛼), uncoupling protein-2 (UCP-2), carnitine palmitoyltransferase 1A (CPT-1A), and histology of liver and epididymal fat were measured and analysed. Body weight gain, FER, liver and epididymal fat weight of IMS groups were significantly decreased. There were significant improvements in blood lipids with less TG, TC, LDL-cholesterol, VLDL-cholesterol and more HDL-cholesterol. Proteins associated with lipid synthesis (SREBP-1, p-ACC, FAS, SCD-1) and cholesterol (SREBP-2, HMGCR) was improved. Factors regulating lipid synthesis and lipid catabolism (p-LKBI, p-AMPK, PPARα, PGC-1α, UCP-2, CPT-1A) were increased. In histological examinations, IMS group had smaller fat droplets than control group. All results increased depending on concentration. Conclusions It can be suggested that IMS has anti-obesity effects with improving lipid metabolism.

• 한국식품저장유통학회지
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• 제31권1호
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• pp.161-172
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• 2024

본 연구에서는 모싯잎 에탄올 추출물이 첨가된 산업용 배지에 유산균(L. plantarum JBLAB0101와 L. rhamnosus GG(LGG)) 발효특성을 확인하였고, 발효물에 대한 항비만 효능 분석을 수행하였다. 유산균 발효기간 중 이화학적특성(pH, 총산도), 생균수, 유기산 및 유리당 함량을 분석하였다. 생균수는 발효 4일 차에 최대치로 8.75-8.85 log CFU/mL로 확인되었으며, 이에 따라 pH는 6.58-6.66에서 3.74-3.79로 감소하였고, 총산도는 0.39-0.40%에서 2.07-2.19%로 증가하였다. Lactic acid는 발효 4일 차에 1,676.03-1,910.12 mg%로 증가하였으며, glucose는 L. plantarum 균주에서 모두 소모되었고, LGG 균주는 348.35 mg% 잔존하였다. 항비만 효능 평가는 pancreatic lipase 저해활성과 3T3-L1 세포주를 이용한 지질분화억제능(지질축적률, 렙틴 생성량 및 PPAR-γ 및 SREBP-1c 유전자의 mRNA 발현량)을 분석하였다. 모싯잎 추출물 첨가 산업용 배지에 접종된 균주의 이름과 배양유무에 따라 비발효물(UFRL), JBLAB0101 발효물(FRLPLA) 및 LGG 발효물(FRLLGG)로 구분하였다. Lipase 저해활성은 UFRL, FRLPLA 및 FRLLGG을 동일농도 0.5 mg/mL에 처리 시 각각 12.19%, 30.10% 및 25.63%로 확인되었다. 3T3-L1 세포주에 FRLPLA를 200 ㎍/mL 처리함에 따라 비처리구에 비해 지질축적률, 렙틴 생성량, PPAR-γ 및 SREBP-1c 유전자의 mRNA 발현량이 각각 37.54%, 54.64%, 24.18% 및 31.32% 감소하였다. 이와 같은 결과로 항비만 효능이 있는 모싯잎 추출물이 첨가된 산업용 배지에 L. plantarum JBLAB0101 균주와 LGG 균주의 유산발효가 항비만 효능 증진 가능성이 기대된다.

• 셀메드
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• 제8권3호
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• pp.11.1-11.6
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• 2018

In vitro anti-obesity effects of anti-cancer (AC) functional kimchi in differentiated 3T3-L1 adipocytes were studied. We constructed three experimental groups: Control, standardized kimchi (SK), and AC functional kimchi (A-FK) that included active ingredients and Lactobacillus plantarum. Kimchi extracts did not show any cytotoxicity in pre-adipocytes in the concentration range of 1 - 5 mg/mL. A-FK significantly reduced fat droplet formation and absorbance in differentiated 3T3-L1 adipocytes, as shown by Oil red O staining, compared to Control and SK (P < 0.05). SK and A-FK reduced adipo-/lipogenesis related genes such as $C/EBP{\alpha}$, SREBP-1, LPL, and $LXR{\alpha}$ compared to Control (P < 0.05). Especially, A-FK more greatly reduced SREBP-1 and LPL compared to SK (P < 0.05). A-FK up-regulated the ${\beta}$-oxidation related gene CPT-1c and down-regulated the pro-inflammatory cytokine IL-6 compared to Control (P < 0.05). Based on the results, A-FK exhibited anti-obesity effects by inhibiting fat droplet formation and adipo-/lipogenesis related genes by regulating the ${\beta}$-oxidation related gene CPT-1c and pro-inflammatory cytokine IL-6. In previous studies, A-FK kimchi already exhibited a strong anti-cancer effect. These results indicate that A-FK increased anti-obesity activity in this model system due to its functional ingredients and anti-cancer functionality.

• Toxicological Research
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• 제34권1호
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• pp.23-29
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• 2018

Ethanol-induced fat accumulation, the earliest and most common response of the liver to ethanol exposure, may be involved in the pathogenesis of liver diseases. Isoliquiritigenin (ISL), an important constituent of Glycyrrhizae Radix, is a chalcone derivative that exhibits antioxidant, anti-inflammatory, and phytoestrogenic activities. However, the effect of ISL treatment on lipid accumulation in hepatocytes and alcoholic hepatitis remains unclear. Therefore, we evaluated the effect and underlying mechanism of ISL on ethanol-induced hepatic steatosis by treating AML-12 cells with 200 mM ethanol and/or ISL ($0{\sim}50{\mu}M$) for 72 hr. Lipid accumulation was assayed by oil red O staining, and the expression of sirtuin1 (SIRT1), sterol regulatory element-binding protein-1c (SREBP-1c), AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$) was studied by western blotting. Our results indicated that ISL treatment upregulated SIRT1 expression and downregulated SREBP-1c expression in ethanol-treated cells. Similarly, oil red O staining revealed a decrease in ethanol-induced fat accumulation upon co-treatment of ethanol-treated cells with 10, 20, and $50{\mu}M$ of ISL. These findings suggest that ISL can reduce ethanol induced-hepatic lipogenesis by activating the SIRT1-AMPK pathway and thus improve lipid metabolism in alcoholic fatty livers.

• 한방재활의학과학회지
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• 제33권3호
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• pp.33-46
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• 2023

Objectives We investigated anti-obesity effects of Menthae Herba hydrosol in obese mice. Methods Animals were divided into four groups, and treatments were performed for 7 weeks. After the treatment, serum lipid profiles, weight and pathological morphology in liver, kidney, adipose tissue were measured. Also, hepatic protein and gene expression levels of lipid metabolism-related factors were analyzed. Results Body weight was decreased in P3% group. In P1% (group fed high-fat diet and 1% Menthae Herba hydrosol) and P3% (group fed high-fat diet and 3% Menthae Herba hydrosol) group, weight of white adipose tissue, serum levels of triglyceride and blood urea nitrogen were decreased, and weight of muscle was increased. Also, liver, kidney and epididymal adipocyte size were reduced in P1% and P3% group. Adenosine monophosphate-activated protein kinase was increased and sterol regulatory element binding protein-1c (SREBP-1c) was decreased in P3% group. mPeroxisome proliferator-activator receptor-γ, mMonocyte chemotactic protein-1 were decreased in P1% and P3% group. In P3% group, mSREBP-1c was decreased and mCarnitine palmitoyl transferase-1 was increased. And mUncoupling protein 1 in brown adipose tissue was increased. Conclusions These results suggest that Menthae Herba hydrosol has a worthy effect on anti-obesity.

• 생명과학회지
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• 제29권10호
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• pp.1144-1151
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• 2019

비알코올성 지방간은 만성 간 질환으로 비만, 고혈압, 비만, 이상지질혈증과 같은 다양한 대사증후군과 연관되어 있다. 꾸지뽕은 한국을 포함한 동아시아 국가에서 다양한 질병에 사용되는 약용작물로 본 연구에서는 유리지방산에 의해 지방축적이 유도된 세포 내에서 꾸지뽕 열매 추출물의 비알코올성 지방간 개선 효과와 기전을 규명하였다. 꾸지뽕 열매 추출물은 지방 축적 및 중성지방, 콜레스테롤 생성 및 HMG 환원효소의 활성을 억제하였다. 또한 지방생성과 관련된 유전자인 SREBP-1, FAS, SCD-1, SREBP-2의 발현을 억제 하였으며 AMPK의 활성화를 억제하였다. 본 연구결과를 통해서 꾸지뽕 열매 추출물이 유리지방산에 의해 유도된 지방 축적을 억제하고 AMPK/SREBP 신호전달 경로를 조절하여 억제 활성을 나타냄을 밝히며, 비알코올성 지방간의 예방 및 개선을 위한 천연물 소재로 활용될 수 있을 것으로 사료된다.

• 대한본초학회지
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• 제35권5호
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• pp.23-31
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• 2020

Objectives : This study was conducted to evaluate the anti-hyperlipidemia effect of Scutellariae Radix, Aucklandiae Radix and Bupleuri Radix(SAB). Methods : FL83B cells were mouse liver hepatocytes, and we used this cell line. FL83B cells were treated with 0.5 mM oleic acid(OA) for 24 h, SAB extract was treated. After OA treatment, intracellular triglyceride (TG) and free fatty acid contents were measured with AdiopoRed™ assay and Free Fatty Acid Quantitation assay kit, respectively. Further, we evaluated several lipogenesis and metabolic markers such as sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy3-methyl-glutaryl CoA reductase (HMGCR), hormone-sensitive lipase (HSL), carnitine palmitoyltransferase (CPT-1), peroxisome proliferator activated receptor alpha (PPARα), and cluster of differentiation (CD36) using RT-PCR and Western-blot analysis. Results : OA markedly increased intracellular TG and free fatty acid, which plays a key role in reducing hepatic lipid accumulation, in FL83B cells. These increases were alleviated by SAB extract. The mRNA and protein expression of Fatty acid(FA) oxidation factors (CPT-1, PPARα), lipolysis factor(HSL), FA transporter(CD36), cholesterol synthesis factors (HMGCoA) and Lipodenesis (SREBP-1c, FAS, and ACC-1) were significantly increased by treatment of SAB extract in the OA-induced fatty liver cell model. Conclusions : In summary, the treat of SAB extract showed a significant reduction of the influx of fatty acids into hepatocytes, promoted the oxidation of fatty acids, and regulated fat synthesis-related factors, thereby regulating the accumulation of TG and free fatty acids.