• Title/Summary/Keyword: HEP

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Biosynthesis of Novel Glucosides Geldanamycin Analogs by Enzymatic Synthesis

  • Huo, Qiang;Li, Hong-Mei;Lee, Jae Kyoung;Li, Jing;Ma, Tao;Zhang, Xinyu;Dai, Yiqun;Hong, Young-Soo;Wu, Cheng-Zhu
    • Journal of Microbiology and Biotechnology
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    • v.26 no.1
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    • pp.56-60
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    • 2016
  • Two new glucosides (1 and 2) of geldanamycin (GA) analogs were obtained from in vitro glycosylation by UDP-glycosyltransferase (YjiC). Based on spectroscopic (HR-ESI-MS, 1D, and 2D-NMR) analyses, the glucosides were elucidated as 4,5-dihydro-7-O-descarbamoyl-7-hydroxyl GA-7-O-β-D-glucoside (1) and ACDL3172-18-O-β-D-glucoside (2). Furthermore, the water solubility of compounds 1 and 2 was about 215.2 and 90.7 times higher respectively, than that of the substrates. Among compounds 1-4, only 3 showed weak antiproliferative activity against four human tumor cell lines: MDA-MB-231, SMMC7721, HepG2, and SW480 (IC50: 13.6, 15.1, 31.8, and 22.7 μM, respectively).

The expression and secretion of vimentin in the progression of non-alcoholic steatohepatitis

  • Lee, Su Jin;Yoo, Jae Do;Choi, Soo Young;Kwon, Oh-Shin
    • BMB Reports
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    • v.47 no.8
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    • pp.457-462
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    • 2014
  • The pathogenesis of non-alcoholic steatohepatitis (NASH) is not fully understood. In the present study, both in vitro and in vivo vimentin expression and secretion in NASH were investigated. The exposure of palmitate and lipopolysaccharide (LPS) to HepG2 cells enhanced caspase-3 activity and vimentin expression, respectively. The combined effects of both treatments on vimentin expression and caspase-3 activation appeared to be synergic. In contrast, blockade of caspase-3 activity by zVADfmk resulted in a significant reduction of cleaved vimentin and secreted vimentin into the culture supernatant. Similarly, lipid accumulation and inflammation occurred in mice fed a methionine-choline-deficient diet; thus, vimentin expression and serum cleaved vimentin levels were increased. However, vimentin was not significantly upregulated, and no cleavage occurred in mice fed a high-fat diet. It was conclusively determined that lipid accumulation in hepatocytes induces apoptosis through a caspase-3 dependent pathway; whereas, LPS stimulates vimentin expression, leading to its cleavage and secretion. Increased vimentin fragment levels indicated the existence of substantial hepatocellular death via an apoptotic mechanism.

Stereoselective Biotransformation of Timosaponin A-III by Saccharomyces cerevisiae

  • Hu, Yong-Mei;Yu, Zhi-Ling;Fong, Wang-Fun
    • Journal of Microbiology and Biotechnology
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    • v.21 no.6
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    • pp.582-589
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    • 2011
  • Bioconversion of timosaponin A-III (TA-III), one of the major steroidal saponins isolated from the rhizomes of Anemarrhenae asphodeloides Bunge (Liliaceae), was investigated in Saccharomyces cerevisiae. Five bioconversion products, denoted compounds 2-6, were obtained. Biotransformation metabolite 2 was a stereoisomer of TAIII with a specific isotype F-ring and ${\beta}$-ranged $CH_3$-21, which rarely occurs in nature. The structure of 2 was elucidated by extensive spectroscopic analysis (H-H COSY, HSQC, HMBC), as well as by high-resolution mass spectral analysis. The growth inhibitory activity of compounds 1-6 was assayed against four human cancer cell lines, HepG2, H-1299, HT-29, and HCT-116. Compounds 1 and 2 obviously inhibited the growth of the four types of cancer cells with $IC_{50}$ values being less than 19${\mu}M$. A structure-activity relationship is discussed, and the spirostane-ring F in compounds 1 and 2 appears to be the critical bioactive moiety for the cell growth inhibitory property.

DNA Topoisomerases I and II Inhibitory Activity and Cytotoxicity of Compounds from the Stems of Parthenocissus tricuspidata

  • Woo, Mi Hee;Zhao, Bing Tian;Tran, Manh Hung;Jeong, Su Yang;Ma, Eun Sook;Min, Byung Sun
    • Bulletin of the Korean Chemical Society
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    • v.34 no.9
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    • pp.2675-2679
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    • 2013
  • Activity-directed isolation of the methylene chloride fraction from the stems of Parthenocissus tricuspidata have led to the identification of two new compounds (1-2): 1-(2',3',5'-trihydroxyphenyl)-2-(4"-hydroxyphenyl)-ethane-1,2-(E)-epoxide (1, tricuspidatin A) and erythro-1-(3',5'-dihydroxyphenyl)-2-(4"-hydroxyphenyl)-ethane-1,2-diol (2, tricuspidatin B), together with four known compounds (3-6): ${\beta}$-sitosterol (3), nonacosan-1-ol (4), 3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid hexacosyl ester (5) and betulinic acid (6). Their chemical structures were elucidated based on spectroscopic (IR, UV, MS, 1D and 2D NMR) and physicochemical analyses. Compounds 1 and 2 showed strong DNA topoisomerase II inhibitory activity at both concentrations of 20 and $100{\mu}M$. In addition, 3 exhibited strong cytotoxic activity against the HT-29 and HepG2 cancer cell lines, and 6 showed strong cytotoxicity against the HT-29 and MCF-7 ones.

Jinan red ginseng extract inhibits triglyceride synthesis via the regulation of LXR-SCD expression in hepatoma cells

  • Hwang, Seung-mi;Park, Chung-berm
    • Korean Journal of Food Science and Technology
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    • v.51 no.6
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    • pp.558-564
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    • 2019
  • Hypertriglyceridemia is one of the metabolic syndrome that is often observed as a result of lipid abnormalities. It is associated with other lipids, metabolic disorders, cardiovascular disease and liver disease. Korean red ginseng is known to affect obesity, dyslipidemia, liver disease and liver function, but the mechanism of its effect is not clear. This study examined the beneficial effects of hypertriglyceridemia and the mechanism of action of Jinan red ginseng extract (JRG) in hepatoma cells. To measure the levels of triglyceride accumulation, we studied the expression of proteins and mRNAs related to lipidogenesis in hepatoma cells (Huh7 and HepG2). JRG decreases the lipidogenic markers, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding proteins α (C/EBPα) and C/EBPβ which are major regulators of triglyceride synthesis in hepatoma cells. We also found that JRG reduced sterol regulatory element binding proteins 1c (SREBP-1c), C/EBPα and C/EBPβ by regulating liver X receptor (LXR) and stearoyl CoA desaturase (SCD) expressions. In addition, the first-limited step of synthesis triglyceride (TG), glycerol-3-phosphate (G3P) is decreased by JRG. These results suggest that the anti-hypertriglyceride effect of JRG in hepatoma cells could be accompanied with the inhibition of lipidogenic transcription factors by regulating LXR and SCD expression.

Antimutagenicity and Cytotoxicity Effects of Woorimil Wheat Flour Extracts Added with Wild Herb and Seaweed Powder (산채 및 해조분말을 첨가한 우리밀 밀가루 열수출물의 항돌연변이성 및 암세포 성장 억제효과)

  • 함승시;이상영;최면;황보현주
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.27 no.6
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    • pp.1177-1182
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    • 1998
  • The antimutagenic and cancer cell growth inhibitory effects of woorimil contained herb and seaweed powders were examined. While woorimil itself showed only 40% antimutagenic effect on S. typhymurium TA98 against 4NQO(0.15 g/plate), water extracts of mountain herbs and seweeds including Comfrey, wormwood, Kale, Angelica utilis and pine leaves showed 80~90% antimutagenicity. On the other hand, these extracts along with woorimil showed 68 to 80% antimutagenic activities. Low antimutagenic activities of less than 50% were shown when these extracts were tested on TA98 against Trp P 1(0.5 g/plate), but high antimutagenic activities of 80~93.3% were shown on TA100. Water extracts of Capsella bursa pastoris and Allium grayi exhibited 60~80% of the activites in cytotoxicity tests of woorimil water extracts(0.5mg/ml) on human lung carcinoma cell. A549 showed 10% cell growth inhibitory effect. When mixed with Comfrey and Angelica utilis extracts, it showed 23~25% inhibition and other extracts showed only 12~23% inhibition. Cytotoxicity test of woorimil extracts on human liver cancer cell Hep3B revealed 20% inhibition. The additions of pine needle extracts, Angelica utilis and Comfrey showed 33%, 29% and 25% inhibition, respectively. But other extracts showed only 20% inhibition.

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DNA Damage and Micronuclei Induced by Di (2-ethylhexyl) phthalate in Human Breast Carcinoma MCF-7 cells (Di(2-ethylhexyl) phthalate에 의해 유도된 DNA손상과 소핵 형성)

  • 김종원;한의식;박미선;엄미옥;김인숙;전혜승;정해관;심웅섭;오혜영
    • Environmental Mutagens and Carcinogens
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    • v.21 no.1
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    • pp.34-43
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    • 2001
  • Di-2-ethylhexyl phthalate (DEHP) is the most commonly used phthalate ester in polyvinyl chloride formulations including food packing and storage of human blood. DEHP is a well known as non-genotoxic carcinogen and endocrine disrupting chemical (EDC). DEHP have shown all negative results in ICH-guildeline recommended standard genotoxicity test battery. In this study, to assess the clastogenic and DNA damaging effect in human-derived tissue specific cells, DEHP was treated in human derived MCE-7 cells, HepG2 cells, LNCap cells, BeWo cells, MCE-10A cells, and female peripheral blood cells using micronucleus assay and in human breast carcinoma MCF-7 cells up to $1.28$\times$10^{-2}$ M using Comet assay. The in vitro micronucleus assay is a mutagenicity test system for the detection of chemicals which induce the formation of small membrane bound DNA fragment i.e. micronuclei in the cytoplasm of interphase cells, originated from clastogenic and/or aneugenic mechanism. The single cell gel electrophoresis assay (Comet assay) is used to detect DNA strand-breaks and alkaline labile site. In our results, DEHP increased significantly and/or dose-depentently and time-dependently micronucleus frequency at the 6 and 24 hr without metabolic activation system only in MCE-7 cells. DEHP treated with 2 hrs in MCF-7 cells using Comet assay induced DNA damage dose-depentantly.

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Antiviral Effects of Natural Products on the Inhibition of Hepatitis B Virus DNA Replication in 2.2.15 Cell Culture System

  • Nam, Kung-Woo;Chang, Il-Moo;Choi, Jae-Sue;Hwang, Ki-Jun;Mar, Woong-Chon
    • Natural Product Sciences
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    • v.2 no.2
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    • pp.130-136
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    • 1996
  • Evaluation of plant extracts that might inhibit hepatitis B virus (HBV) replication was performed to find potent anti-HBV agents. Eighty-five species of plants from forty-three families were tested for their anti-HBV activities using HBV-producing HepG2-derived 2.2.15 cells. The anti-HBV activity of plant extracts was measured by slot blot hybridization technique and cytotoxicity was determined by crystal violet staining procedure. All plants were extracted with methanol and the extracts were partitioned into n-hexane, ethyl acetate and aqueous layer. The ethyl acetate fractions of Rhus verniciflua $(stem:\;EC_{50},\;8.2{\mu}g/ml;\;CC_{50},\;9.4{\mu}g/ml)$, Gastrodia elata $(root:\;EC_{50},\;17.7{\mu}g/ml;\;CC_{50},\;>20{\mu}g/ml)$, Raphanus sativus $(seeds:\;EC_{50},\;17.3{\mu}g/ml;\;CC_{50},\;>20{\mu}g/ml)$, and Angelica gigas $(root:\;EC_{50},\;8.3{\mu}g/ml;\;CC_{50},\;15.6{\mu}g/ml)$ revealed the anti-HBV activity in 2.2.15 cell culture system and these fractions are under the process of further sequential fractionation by column chromatography to find the active principles against HBV.

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Allozyme Diversity and Population Genetic Structure in Korean Endemic Plant Species : II. Hosta yingeri (Liliaceae)

  • Chung, Myong Gi
    • Journal of Plant Biology
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    • v.37 no.2
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    • pp.141-149
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    • 1994
  • Levels of genetic diversity, population genetic structure, and gene flow in Hosta yingeri, a herbaceous perennial endemic to Taehuksan, Sohuksan, and Hong Islands, were investigated. Starch gel electrophoresis was conducted on leaves for 101 plants collected from three populations. Although the distribution of thespecies is restricted in the islands, it maintains high levels of genetic variatin; 64% of polymorphic loci in at least one population (Ps), the mean number of alleles per locus (Ap) of 1.92, and the mean effective number of alleles per locus (Aep) of 1.52. Overall, mean genetic diversity (Hep=0.250) was substantially higher than mean estimate for species with very similarlife history traits (0.102). Large populaton size, the persistence of multiple generations within populations, high fecundity, predominantly outcrossing breeding system, large size of pollinator visitation areas may be explanatory factors contributing the higher level of genetic diversity maintained within populations. Analysis of fixation indices showed an overall slight excess of heterozygotes (mean FIS=-0.066) relative to Hardy-Weinberg expectations, which may in part be due to the near self-incompatible breeding system in the species. Significant differences in allele frequencies among populaitns were found for 14 out of 16 polymorphic loci (P<0.05). Slightly more than 80% of the total variation in the species was common to all populations (GST=0.198). As expected, indirect estimate of the number of migrants per generation (Nm=0.45, calculated from mean GST) and nine private alleles found in the three populations indicate that gene movement among three isolated island populations was low.

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Effects of Ampelopsis japonica Extracts on Tumor Immunity (백렴 추출물(抽出物)이 종양면역(腫瘍免疫)에 미치는 영향)

  • Park, Seung-Man;Ahn, Sang-Woo;Cho, Jong-Kwan
    • Korean Journal of Oriental Medicine
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    • v.11 no.2
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    • pp.113-140
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    • 2005
  • 1. 백렴 추출물은 부분적으로 종양세포인 HT1080, Hep G2, MCF-7 cell에 대해 세포독성을 보였으나, 섬유세포인 7250 cells과 종양세포인 CT-26 cells에서는 세포독성은 나타나지 않았다. 2. 백렴 추출물은 macrophage에서 생산되는 NO production을 부분적으로 증가시켰다. 3. 백렴 추출물은 macrophage 활성화와 관련 있는 IL-1과 iNOS의 유전자 발현을 증가시켰다. 4. 백렴 추출물은 NK cell의 cytotoxicity를 활성화시켰다. 5. 백렴 추출물은 NK cell 활성화와 관련있는 IL-1, IL-4, IL-10, IL-12, iNOS, IFN-${\gamma}$, TNF-${\alpha}$ 의 유전자 발현을 증가시켰다. 6. 백렴 추출물은 마우스의 비장세포에서 IL-10, IFN-${\gamma}$, TNF-${\alpha}$ 의 단백질 발현을 증가시켰다. 7. 백렴 추출물은 CT-26 cell에 의한 pulmonary colony를 대조군에 비해 유의성 있게 억제시켰다. 이상의 결과로 백렴 추출물은 macrophage와 NK cell의 활성화를 통해 면역 조절과 항암제로서의 유용성이 기대된다.

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