• YAKHAK HOEJI
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• 제53권5호
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• pp.286-292
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• 2009

In this study, we investigated the anti-obese activity of HPJ extract in C57BL/6J mice. The C57BL/6J mice were randomly divided into five groups: normal control group (Con), high fat diet control group (HFD), treatment groups with HPJ at 125 mg/kg (HPJ125), 250 mg/kg (HPJ250), or 500 mg/kg (HPJ500). To induce an obesity, mice were fed by a high fat diet for 6 weeks, and mice were administered with HPJ extract once a day for 8 weeks. At the end of treatment, we examined the effect of HPJ extract on body weight, plasma lipid, and lipogenic enzymes. HPJ extract was found to lower whole body and epididymal adipose tissue weights and lowered plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), non-esterified fatty acid (NEFA) and leptin, compared to those in HFD group. Histological analyses of the liver and fat tissues of mice treated with HPJ extract revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the HFD group. In addition, HPJ extract preserved the morphological integrity of pancreatic islets. To elucidate an action mechanism of HPJ extract, Western blot and RT-PCR were performed using epididymal adipose tissues. HPJ extract up-regulated the levels of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylasse (ACC). HPJ extract also attenuated lipogenic gene expressions of sterol regulatory element-binding protein $1{\alpha}$ (SREBP$1{\alpha}$), fatty acid synthase (FAS), sterol-CoA desaturase 1 (SCD1) and glycerol-3-phosphate acyltransferase (GPAT) in dose-dependent manners. In contrast, expressions of lipolytic genes such as peroxisome proliferator-activated receptor-$\alpha$ (PPAR-${\alpha}$) and CD36, and fatty acid $\beta$-oxidation gene, carnitine palmitoyltransferase-1 (CPT-1) were increased. These results suggest that HPJ extract ameliorates obesity through inhibiting synthesis of lipogenic enzymes as well as stimulating fatty acid oxidation resulting from activation of AMPK, and HPJ extract could be developed as a potential therapeutic agent for obese patients.

• Journal of Life Science
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• 제25권11호
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• pp.1255-1264
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• 2015

Cnidium officinale, a traditional herb, has diverse beneficial pharmacological activities, such as anti-inflammatory, antioxidant, anticancer, and antiangiogenesis effects. However, the cellular and molecular mechanisms of apoptosis by C. officinale are poorly defined. The present study investigated the proapoptotic effects of water, ethanol, and methanol extract of C. officinale (WECO, EECO, and MECO, respectively) in human leukemia U937 cells. The antiproliferative activity of EECO was higher than that of WECO and MECO. The antiproliferative effect of EECO treatment in U937 cells was associated with the induction of apoptotic cell death, including increased populations of annexin-V positive cells, the formation of apoptotic bodies, DNA fragmentation, and increased numbers of cells with a loss of mitochondrial membrane potential (MMP, Δψm). EECO-induced apoptotic cell death was associated with upregulation of death receptor 4 (DR4) and down-regulation of cellular inhibitor of apoptosis protein-1 (cIAP-1), Bcl-2, and total Bid. The EECO treatment also induced the proteolytic activation of caspases (-3, -8, and -9), and degradation of caspase-3 substrate proteins, such as poly(ADP-ribose) polymerase (PARP), β-catenin, and phospholipase C-γ1 (PLCγ1). In addition, the EECO treatment effectively activated the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. However, compound C, a specific inhibitor of AMPK, significantly reduced EECO-induced apoptosis. These results indicate that AMPK is a key regulator of apoptosis in response to EECO in human leukemia U937 cells.

• Journal of Microbiology and Biotechnology
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• 제23권5호
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• pp.637-643
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• 2013

We have demonstrated that 1-deoxynojirimycin (DNJ) isolated from Bacillus subtilis MORI could enhance the levels of adiponectin and its receptors in differentiated 3T3-L1 adipocytes, which has been shown to be effective in lowering blood glucose levels and enhancing insulin sensitivity. DNJ was not toxic to differentiated 3T3-L1 adipocytes for up to a concentration of $5{\mu}M$. In terms of expression levels of adiponectin and its receptors (AdipoR1 and AdipoR2), DNJ in concentrations as low as $0.5{\mu}M$ elevated both mRNA and protein levels of adiponectin and transcript levels of AdipoR1 and AdipoR2. In addition, DNJ increased phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) in a statistically significant manner. Finally, treatment with DNJ resulted in increased mRNA expression of glucose transporter 4 (GLUT4), which encodes for a glucose transporter, along with a significant increase in glucose uptake into the adipocytes based on results of a 2-deoxy-D-[$^3H$] glucose uptake assay. Our findings indicate that DNJ may greatly facilitate glucose uptake into adipose tissues by increasing the action of adiponectin via its up-regulated expression as well as its receptor genes. In addition, the glucose-lowering effects of DNJ may be achieved by an increased abundance of GLUT4 protein in the plasma membrane, as a consequence of the increased transcript levels of the GLUT4 gene and the activation of AMPK.

• Journal of Life Science
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• 제29권10호
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• pp.1144-1151
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• 2019

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with various metabolic syndromes, such as obesity, dyslipidemia, hypertension, and diabetes. Cudrania tricuspidata is a medicinal plant distributed widely in Asia and has been used in clinical practice to treat various diseases. The aim of this study is to determine the lipid-lowering effects of C. tricuspidata fruit extract (CTE) using a cell model induced by free fatty acids (FFAs). HepG2 cells were exposed to 1mM FFAs (palmitic acid:oleic acid = 2:1) for 24 hr to simulate the conditions of NAFLD in vitro. CTE attenuated the increases of lipid accumulation, intracellular triglyceride, and cholesterol content and inhibited 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) activity in the HepG2 cells in a dose-dependent manner. Also, CTE inhibited the protein expression of lipogenesis-related genes, such as sterol regulatory element-binding protein-1/-2 (SREBP-1/-2), fatty acid synthase (FAS), and stearoyl CoA desaturase-1 (SCD-1) in FFAs-induced lipid accumulation in HepG2 cells. In addition, CTE-induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in HepG2 cells. These results suggest that CTE attenuates hepatic lipid accumulation by inhibiting lipogenesis through the modulation of the AMPK signaling pathway on FFAs-induced lipogenesis in HepG2 cells and may potentially prevent NAFLD.

• Journal of Nutrition and Health
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• 제57권1호
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• pp.16-26
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• 2024

Purpose: Type 2 diabetes mellitus is a metabolic condition marked by persistent elevated blood sugar levels resulting from insulin resistance. The effective management of diabetes mellitus involves strict regulation of the blood glucose levels. This study examined the effects of Autumn olive (Elaeagnus umbellata Thunb.) berry (AOB) on insulin resistance and hyperglycemia using a type 2 diabetes mellitus animal model. Methods: Eight-week-old C57BL/6J mice were divided into four groups. The control group received a basal diet, while the high-fat, high-sucrose (HFHS) group was fed a HFHS diet containing 27% sucrose and 33% lard for 12 weeks. The low AOB (LAOB) and high AOB (HAOB) groups were offered a HFHS diet with a 0.5% and 1.0% AOB extract, respectively. Results: The HAOB group showed significantly lower epididymal fat pad weight than the HFHS group. The LAOB and HAOB groups showed lower serum glucose levels and homeostasis model assessment for insulin resistance values than the HFHS group, and the HAOB group has lower serum insulin levels than the HFHS group. Supplementation with HAOB decreased serum cholesterol levels significantly compared with the HFHS group. The consumption of LAOB and HAOB reduced the serum triglyceride and hepatic total lipids and triglyceride levels compared to the HFHS group. In addition, LAOB and HAOB consumption in mice fed a HFHS diet increased adenosine monophosphate-activated protein kinase protein expression. Insulin receptor substrate-2 protein expression in the HAOB group was significantly higher than the HFHS group. Conclusion: AOB can alleviate hyperglycemia in type 2 diabetes mellitus partly by mitigating insulin resistance.

• Journal of Korean Medicine for Obesity Research
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• 제23권2호
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• pp.60-68
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• 2023

Objectives: This study was conducted to compare the effects of Hominis placenta (Jahage, J) and wild ginseng (SanSam, S) pharmacopuncture drugs on muscle differentiation and energy metabolism regulation in C2C12 myotubes. Methods: The C2C12 myoblasts were differentiated into myotubes for 5 days by replacing in medium containing 2% horse serum and then treated with J and S pharmacopuncture extract at different concentrations for 24 hr. The expression of myosin heavy chain and energy metabolism-regulating factors, myosin heavy chain (MHC), nuclear respiratory factor-1 (NRF-1), and proliferator-activated receptor γ coactivator-1 alpha (PGC-1α) were determined in C2C12 myotubes by western blot. Additionally, the phosphorylation of AMPK and the expression of mitochondrial biogenesis, including sirtuin 1 (SIRT1) were determined in the myotubes. Results: As a result, treatment with J and S pharmacopuncture extract at 0.1 and 1 mg/mL increased the MHC expression in C2C12 myotubes compared with non-treated cells, but only S pharmacopuncture was shown a significant and distinct increase in the expression. Expression of TFAM and NRF-1 was also shown significant increases in S and J pharmacopuncture in C2C12 myotubes compared to non-treated cells. The phosphorylation of AMPK and the expression of PGC-1α and SIRT1 showed increased expression in S and J pharmacopuncture compared to non-treated cells. The effect of low-dose of J pharmacopuncture on the phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and PGC-1α expression was greater than that of S pharmacopuncture. Conclusions: In conclusion, both J and S pharmacopuncture promote muscle differentiation in C2C12 myoblasts into myotubes and energy metabolism through the AMPK/SIRT1 signaling pathway. This indicates that the pharmacopuncture with tonic herbal medicines can help to improve skeletal muscle function.

• Animal Bioscience
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• 제34권3_spc호
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• pp.385-392
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• 2021

Objective: The present study was conducted to investigate the effects of lycopene on growth performance, abdominal fat deposition, serum lipids levels, activities of hepatic lipid metabolism related enzymes and genes expression in broiler chickens. Methods: A total of 256 healthy one-day-old male Arbor Acres broiler chicks were randomly divided into four groups with eight replicates of eight birds each. Birds were fed basal diet supplemented with 0 (control), 100, 200, and 400 mg/kg lycopene, respectively. Results: Dietary 100 mg/kg lycopene increased the body weight at 21 day of age compared to the control group (p<0.05). Compared to the basal diet, broilers fed diet with 100 mg/kg lycopene had decreased abdominal fat weight, and broilers fed diet with 100 and 200 mg/kg lycopene had decreased abdominal fat percentage (p<0.05). Compared to control, diets with 100, 200, and 400 mg/kg lycopene reduced the levels of total triglyceride and total cholesterol in serum, and diets with 100 and 200 mg/kg lycopene reduced the level of serum low density lipoprotein cholesterol (p<0.05). The activity of fatty acid synthase (FAS) in 400 mg/kg lycopene treated broilers and the activity of acetyl-CoA carboxylase (ACC) in 100, 200, and 400 mg/kg lycopene treated broilers were lower than those fed basal diet (p<0.05). Lycopene increased the mRNA abundance of adenosine monophosphate activated protein kinase α (AMPK-α), whereas decreased the mRNA abundance of sterol regulatory element-binding protein 1, FAS, and ACC compared to the control group (p<0.05). Conclusion: Dietary lycopene supplementation can alleviate abdominal fat deposition and decrease serum lipids levels, possibly through activating the AMPK signaling pathway, thereby regulating lipid metabolism such as lipogenesis. Therefore, lycopene or lycopene-rich plant materials might be added to poultry feed to regulate lipid metabolism.

• Journal of Life Science
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• 제33권4호
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• pp.343-348
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• 2023

Acne is one of the most common skin diseases, mainly occurring in adolescence. The pathophysiology of acne involves not only hormonal, genetic and environmental factors, but also other factors including hyperseborrhea, inflammation, over-keratinization of follicular keratinocytes and overgrowth of Cutibacterium acnes (C. acnes). Cannabidiol (CBD) is known to relieve pain, stress and inflammation. Moreover, cannabis extracts containing CBD have been reported to be effective in treating acne. However, the therapeutic effect of CBD on acne remains unclear. Therefore, this study aimed to investigate the effect and mechanism of CBD on lipogenesis in SEB-1 sebocytes. We treated sebocytes with CBD and found that it not only inhibited lipid synthesis, but also inhibited cell proliferation by inducing apoptosis. We then demonstrated that sterol response element-binding protein-1 (SREBP-1) mediates the inhibitory effect of CBD on lipogenesis. Furthermore, Akt and adenosine monophosphate-activated protein kinase (AMPK), upstream regulators of SREBP-1, were regulated by CBD treatment. Taken together, our studies demonstrate that CBD inhibits adipogenesis by regulating the Akt/AMPK-SREBP-1 signaling pathway, providing potential for use as a therapeutic agent for acne. Further research is needed to confirm the effect of CBD on inflammation caused by hyperkeratosis, which will increase the possibility of using CBD for acne treatment.

• Journal of Life Science
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• 제29권4호
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• pp.410-420
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• 2019

Citrus unshiu peel extracts possess a variety of beneficial effects, and studies on their anticancer activity have been reported. However, the exact mechanisms underlying this activity remain unclear. In the current study, the apoptotic effect of ethanol extract of C. unshiu peel (EECU) on human breast adenocarcinoma MDA-MB-231 cells and related mechanisms were investigated. The results showed that the survival rate of MDA-MB-231 cells treated with EECU was significantly inhibited in a concentration-dependent manner, which was associated with the induction of apoptosis. EECU-induced apoptosis was associated with the activation of caspase-8 and caspase-9, which initiate extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3, a representative effect caspase. EECU suppressed the expression of the inhibitor of apoptosis family of proteins, leading to an increased Bax/Bcl-2 ratio and proteolytic degradation of poly (ADP-ribose) polymerase. EECU also enhanced the loss of the mitochondrial membrane potential and cytochrome c release from the mitochondria to the cytosol, along with truncation of Bid. In addition, EECU activated AMP-activated protein kinase (AMPK), and compound C, an AMPK inhibitor, significantly weakened EECU-induced apoptosis and cell viability reduction. Furthermore, EECU promoted the generation of reactive oxygen species (ROS), which acted as upstream signals for AMPK activation as pretreatment of cells, with the antioxidant N-acetyl cysteine reversing both EECU-induced AMPK activation and apoptosis. Collectively, these findings suggest that EECU inhibits MDA-MB-231 adenocarcinoma cell proliferation by activating intrinsic and extrinsic apoptotic pathways, which was mediated through ROS/AMPK-dependent pathways.

• Asian-Australasian Journal of Animal Sciences
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• 제21권4호
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• pp.471-477
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• 2008

The porcine PRKAG3 (RN) gene encodes the regulatory gamma subunit of adenosine monophosphate-activated protein kinase (AMPK), which is a good candidate gene affecting meat quality. In this study, the effects of two missense mutations A595G (Ile199Val) and G154A (Gly52Ser) in porcine PRKAG3 gene on meat quality traits were studied in M. Longissimus dorsi (LD), M. Semispinalis capitis (SC) and M. Biceps femoris (BF) from different populations of 326 pigs. The PRKAG3 alleles 199I, 199IV, 52S and 52G were identified with PCR-RFLPs and all genotypes - 199I/199I, 199I/199V, 199V/199V, 52S/52S, 52S/52G and 52G/52G - were found. The frequency of V allele was larger than that of I allele in all populations. I allele frequency was zero in Chinese Meishan pigs (population D) especially. G allele frequency was larger than that of S allele in all populations except Large White (population A). Both variations at the PRKAG3 locus significantly affected these meat quality traits. The pork meat quality has not previously been established in Meishan or crosses thereof. The results suggested that generally pH of LD, SC and BF was higher in Meishan pigs than that in other populations. Moreover, Meishan pigs showed higher water-holding capacity and intramuscular fat (IMF), lower water content and water loss percentage compared to other populations in terms of the two variations. The results present here supply new evidence that alleles V199I and G52S at the PRKAG3 locus affect pork meat quality and provide useful information on pork production.