• Title/Summary/Keyword: HEP

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Licochalcone Suppresses LXRα-Induced Hepatic Lipogenic Gene Expression through AMPK/Sirt1 Pathway Activation

  • Han, Jae Yun;Park, Sun Hee;Yang, Ji Hye;Kim, Mi Gwang;Cho, Seung Sik;Yoon, Goo;Cheon, Seung Hoon;Ki, Sung Hwan
    • Toxicological Research
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    • v.30 no.1
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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.

Hepaprotective Effect of Standardized Ecklonia stolonifera Formulation on CCl4-Induced Liver Injury in Sprague-Dawley Rats

  • Byun, Jae-Hyuk;Kim, Jun;Choung, Se-Young
    • Biomolecules & Therapeutics
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    • v.26 no.2
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    • pp.218-223
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    • 2018
  • The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride ($CCl_4$)-induced liver injury in Sprague Dawley rat. Sixty rats were randomly divided into six groups. The rats were treated orally with ES formulation and silymarin (served as positive control, only 100 mg/kg/day) at a dose of 50, 100, or 200 mg/kg/day for 21 days. Seven days after treatment, liver injury was induced by intraperitoneal injection of $CCl_4$ (1.5 ml/kg, twice a week for 14 days). The administration of $CCl_4$ exhibited significant elevation of hepatic enzymes (like AST and ALT), and decrease of antioxidant related enzymes (superoxide dismutase, glutathione peroxidase and catalase) and glutathione. Then, it leaded to DNA damages (8-oxo-2'-deoxyguanosine) and lipid peroxidation (malondialdehyde). Administration of ES formulation inhibited imbalance of above factors compared to $CCl_4$ induced rat in a dose dependent manner. Real time PCR analysis indicates that CYP2E1 was upregulated in $CCl_4$ induced rat. However, increased gene expression was compromised by ES formulation treatment. These findings suggests that ES formulation could protect hepatotoxicity caused by $CCl_4$ via two pathways: elevation of antioxidant enzymes and normalization of CYP2E1 enzyme.

Quantitative analysis of gene expression pattern in aspergillus nidulans mycelia by sequencing of 3-directed cDNA clones

  • Park. Yoon-Dong;Lee, Dong-Whan;Lee, Seog-Jae;Kim, Jong-Hwa;Chae, Keon-Sang
    • Journal of Microbiology
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    • v.34 no.1
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    • pp.25-29
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    • 1996
  • Since sequencing of randomly selected cDNA clones has been known to be a powerful approach to obtain information on gene expression pattern in specific cells or tissues, we have analyzed a 3'-directed cDNA library of vegetative mycelia of A. nidulans by single-pass sequencing of hundreds of randomly selected clones. Sequencing of 292 cDNA clones yielded 209 gene signatures (GSs) probably representing highly or lesser expressed genes in the vegetative mycelia. Among the 209 GSs, 25 (79 cDNA clones) appeared more than once and 184 only once. One GS appeared at a highest frequency of 6 times, 2 GSs5 times, 4 GSs 4 times, a GSs 3 times and 16 GSs twice. About 6.6% GSs comprizing of 13 GSs showed alternative polyadenylation. Among 23 redundant GSs, three were common in both mycelia and sexual organs, and 22 were probably mycelia-specific. Out of 209 GSs, 36 were identified in GenBank showing of 70% or greater similaritis. Only six GSs were for A. nidulans genes, and 13 GSs were of DNA or genes encoding cytoplasmic or organellar proteins. This pattern is similar to those in the human HepG2 cell line and in human colonic mucosa, although very few genes for nuclear proteins and for protein synthesis were in A. nidulans.

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Genetic Diversity and Population Structure of Chimaphila japonica in Southern Part of Korea (한국 남부지역의 매화노루발의 유전적 다양성과 집단구조)

  • Joo-Soo Choi;Man-Kyu Huh
    • Journal of Life Science
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    • v.8 no.6
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    • pp.687-694
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    • 1998
  • Enzyme electrophoresis was used to estimate genetic diversity and population structure of Chimaphila japonica Miq. in Korea. The percent of polymorphic loci within the enzymes was 48.7%. Genetic diversity at the species level and at the population level was high (Hes=0.278 ; Hep=0.222, respectively), whereas the extent of the population divergence was relatively low ( $G_{ST}$ =0.079). $F_{IS}$ , a measure of the deviation from random mating within the 7 populations, was 0.355. An indirect estimate of the number of migrants per generation (Nm=2.61) indicates that gene flow is high among Korean populations of the species. In addition, analysis of fixation indices revealed a substantial heterozygosity deficiency in some populations and at some loci. Factors contributing to the high levels of genetic dive-rsity found in the entire species of C. japonica include wide distribution, long-lived perennials, ability to regenerate due to rhizomatous spread, outcrossing induced by animal vectors, and occasional pollen dispersal by wind.

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Mutagenic and Antimutagenic Effects of Hemp Seed Oil Evaluated by Ames Salmonella Testing (삼종실유의 항돌연변이 효과)

  • Jeun, Jung-Ae;Cho, Hee-Joon;Jun, Hee-Jin;Lee, Ji-Hae;Jia, Yao-Yao;Cho, Kyoung-Sang;Kim, Eun-Soo;Lee, Sung-Joon
    • Korean Journal of Food Science and Technology
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    • v.43 no.3
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    • pp.396-400
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    • 2011
  • We examined the in vitro mutagenic and antimutagenic effects of hexane-extracted hemp (Cannabis sativa L. subsp. sativa var. sativa) seed oil (HO) with and without S9-mediated metabolic activation, using the TA98 and TA100 Salmonella Typhimurium strains. The MTT assay revealed no cytotoxicity in HepG2 cells for HO quantities $\leq400g$/mL. In the mutagenicity test, revertant colonies did not exceed spontaneous colonies in number. Colony numbers did not increase in either strain after HO treatment, with or without metabolic activation. HO showed no mutagenic effects and did not induce a mutation in either strain. In the antimutagenicity test, HO reduced the number of mutated colonies induced by 4NQO in both strains. The inhibition rates of HO (TA98, 21-91%; TA100, 21-85%) indicated a potent reduction in mutagenicity induced by 4NQO. HO showed no significant mutagenicity and may have antimutagenic effects, as assessed by Ames testing.

ACE, α-Glucosidase and Cancer Cell Growth Inhibitory Activities of Extracts and Fractions from Marine Microalgae, Nannochloropsis oculata (해양 미세조류 Nannochloropsis oculata 추출.분획물의 ACE, α-glucosidase 및 암세포 저해 활성)

  • Cha, Seon-Heui;Kim, Min-Joo;Yang, Hye-Young;Jin, Chang-Beum;Jeon, You-Jin;Oda, Tatsuya;Kim, Dae-Kyung
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.43 no.5
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    • pp.437-444
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    • 2010
  • Extracts of the marine microalgae Nannochloropsis oculata were obtained using 80% methanol (MeOH) and water. The 80% MeOH extract was further fractionated with n-hexane, chloroform, ethyl acetate (EtOAc), n-butanol (n-BuOH), and water to isolate the active fraction. Seven samples were prepared and their angiotensin converting enzyme (ACE), $\alpha$-glucosidase, and cancer cell growth inhibitory activities in vitro were determined. The most profound ACE inhibitory activity was observed in the chloroform fraction, while the others had moderate effects. By contrast, greater $\alpha$-glucosidase inhibitory activity was found in the EtOAc fraction, n-hexane fraction, and water extract of N. oculata. The antiproliferative effects of the extracts and fractions against HL-60, U937, CT-26, and SK-Hep1 cancer cells were also determined. The n-BuOH fraction had the strongest antiproliferative effects on CT-26 cells in a time-dependant manner (P<0.05). These results suggest that the extracts and fractions from N. oculata could be used as a potential functional food or as pharmaceutical ingredients.

Antioxidant Effect and Liver Protection Effect of Spatholobi Caulis Water Extract (계혈등 물추출물의 항산화 및 간보호효과)

  • Lee, Jae-Jun;Choi, Hong-Sik;Kim, Seung-Mo
    • The Korea Journal of Herbology
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    • v.26 no.3
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    • pp.47-56
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    • 2011
  • Objectives : This study investigated whether the water extract of Spatholobi Caulis (SCE) has the ability to protect hepatocyte against oxidative stress induced by tert-butylhydroperoxide (tBHP) in vitro and $CCl_4$ in vivo. Methods : In vitro, HepG2 cells pre-treated with Spatholobi Caulis water extract (1, 3, 10, $30{\mu}g$/ml) for 12h and further incubated with tBHP ($100{\mu}M$) for the next 12h. Cell viability was assessed by MTT assay. In vivo, rats were orally administrated with the aqueous extract of Spatholobi Caulis (SCE; 50, 100 mg/kg) for 4 days and then, injected with $CCl_4$ 1 mg/kg body weight to induce acute liver damage. Results : Treatment with SCE inhibited cell death induced by tBHP, as evidenced by alterations in the levels of the proteins associated with apoptosis:SCE prevented a decrease in $Bcl_2$, and cleavage of poly(ADP-ribose)polymerase and pro-caspase-3. Moreover, SCE inhibited the ability of tBHP to generate $H_2O_2$ production, thereby restoring GSH content. Moreover, SCE treatments in rats effectively decreased liver injuries induced by a single dose of $CCl_4$, as evidenced by decreases in hepatic degeneration and inflammation as well as plasma alanine aminotransferase and lactate dehydrogenase activities. Consistently, treatments of SCE also protected liver in rats stimulated by $CCl_4$, as indicated by restoration GSH and prevention of MDA in the liver. Conclusions : SCE has the ability 1) to protect hepatocyte against oxidative stress induced by tBHP and 2) to prevent $CCl_4$-inducible acute liver toxicity. Present findings may be informative not only in elucidating the pharmacological mechanism of Spatholobi Caulis, but in determining its potential application for oxidative cellular damage in the liver.

Protective Effect of Cortex Fraxini on Heart Injury in a Rat Model of Myocardial Infarction (흰쥐를 이용한 심근경색모델에서 진피(秦皮)의 심장손상 보호효과)

  • Lim, Sun-Ha;Lee, Jong-Won
    • The Korea Journal of Herbology
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    • v.26 no.4
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    • pp.149-154
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    • 2011
  • Objectives : Myocardial infarction is caused by heart cell death in a region where coronary arteries supplying blood to the region are occluded. In the present study, we determined whether ethanol extract of Cortex fraxini (HY5053) could attenuate heart injury by inhibiting apoptosis. Methods : Improvement of survival of HepG2 cells, a human hepatocellular carcinoma cell line, and reduction of apoptosis under hypoxic conditions (3% $O_2$) were assessed by trypan blue staining and DNA fragmentation assay, respectively. To assess the impact of HY5053 on the heart injury, Sprague-Dawley rats underwent 1 day of the left anterior descending coronary artery occlusion. HY5053 was given by intraperitoneal injection (200 mg/kg) 1 hr prior to the occlusion. Subsequently, the heart were harvested, excised into 4 slices, and the slices were stained with 2,3,5-triphenyl tetrazolium chloride. Finally, the extent of heart injury represented as ischemic index (%) was assessed. Results : Addition of HY5053 (400 ${\mu}g$/mL) into the culture medium for 1 day under ischemic conditions improved the cell survival by 50%, compared with control (0 ${\mu}g$/mL), consequently delayed apoptosis in 6 hr difference. Also, HY5053 (200 mg/kg) reduced the ischemic index by 44%, compared with control (0 mg/kg). Conclusions : These findings suggested that HY5053 attenuated myocardial infarction by inhibiting apoptosis. Thus, Cortex fraxini could be developed as a novel cardioprotectant to complement a currently available treatment, coronary angioplasty.

Interaction of Different Types of Cells on Poly(L-lactide-co-glycolide) Surface with Wettability Chemogradient

  • Gilson Khang;John M. Rhee;Lee, Jin-Ho;Lee, Ilwoo;Lee, Hai-Bang
    • Macromolecular Research
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    • v.8 no.6
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    • pp.276-284
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    • 2000
  • A wettability chemogradient on poly(L-lactide-co-glycolide) (PLGA) films was prepared by treating the films in air with corona from a knife-type electrode whose power increases gradually along the sample length. The PLGA surfaces oxidized gradually with the increasing corona power, and the wettability chemogradient was created on the surfaces as evidenced by the measurement of water contact angles and electron spectroscopy for chemical analysis. The wettability chemogradient PLGA surfaces were used to investigate the interaction of four different types of cells such as hepatoma (Hep G2), osteoblast (MG 63), bovine aortic endothelial (CPAE), and fibroblast (NIH/3T3) cells in terms of the surface hydrophilicity/hydrophobicity of PLGA. The cells adhered and grown on the chemogradient surface along the sample length were counted and observed by scanning electron microscopy. It was observed that the cells were adhered, spread, and grown more onto the positions with moderate hydrophilicity of the wettability chemogradient PLGA surface than the more hydrophobic or hydrophillic positions, regardless of the cell types used. The maximum adhesion and growth of the cells appeared at around water contact angles of 53~55°. This result seems closely related with the serum protein adsorption on the surface; the serum proteins were also adsorbed more onto the positions with moderate hydrophilicity of the wettability chemogradient surface. It seems that the wettability plays important roles for cell adhesion, spreading and growth on the PLGA surface. The surface modification technique used in this study may be applicable tothe area of tissue engineering for the improvement of tissue compatibility of films- or scaffold-type substrates.

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Effects of Propolis on Tumoricidal Activities (Propolis가 종양 억제작용에 미치는 영향)

  • Kwon Myung-Sang;Kim Young-Hwu;Cho Jung-Soon
    • Journal of the East Asian Society of Dietary Life
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    • v.15 no.5
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    • pp.542-548
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    • 2005
  • In recent years, propolis has attracted much attention as an useful substance in medicine and functional food, even if it is known as a natural remedy in folk medicine since ancient times. propolis was registered as natural food since 1995 on Korean Food Act by Korean Food and Drug Administration(KFDA). The present study demonstrated the optimization of isolation of crude propolis by ethanol, and tumoricidal effect of pro polis. The optimal concentration of ethanol to separate a high quantity of propolis was $60\%$. The cytotoxic effect of ethanol extracted propolis against various cancer cell lines including murine lymphoma (Sarcoma-180), murine T-lymphoma (YAC-1), human breast carcinoma (MCF-7), human gastric carcinoma (KATOIII) and human hepatocellular carcinoma (Hep3B) and human lung adenocarcinoma (A-549) was observed using SRB and MIT assay. In order to investigate the curative activity by oral administration of propolis on tumor, ICR mice was subcutaneously implanted Sarcoma 180. In 300mg/kg and 600mg/kg propolis administered group, development of implanted tumors was inhibited by $40.9\%\;and\;67.9\%$ at 16th day, respectively. In the same dose of propolis administered group, development of implanted tumors was inhibited more strongly with dose dependent manner. Therefore, these data suggested propolis may show tumoricidal effects. In conclusion, these results indicate that propolis, one of the few natural remedies, can be used as functional food with tumoricidal effects.

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