• Title/Summary/Keyword: RG3

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Identification of High Affinity Non-Peptidic Small Molecule Inhibitors of MDM2-p53 Interactions through Structure-Based Virtual Screening Strategies

  • Bandaru, Srinivas;Ponnala, Deepika;Lakkaraju, Chandana;Bhukya, Chaitanya Kumar;Shaheen, Uzma;Nayarisseri, Anuraj
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3759-3765
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    • 2015
  • Background: Approaches in disruption of MDM2-p53 interactions have now emerged as an important therapeutic strategy in resurrecting wild type p53 functional status. The present study highlights virtual screening strategies in identification of high affinity small molecule non-peptidic inhibitors. Nutlin3A and RG7112 belonging to compound class of Cis-imidazoline, MI219 of Spiro-oxindole class and Benzodiazepine derived TDP 665759 served as query small molecules for similarity search with a threshold of 95%. The query molecules and the similar molecules corresponding to each query were docked at the transactivation binding cleft of MDM2 protein. Aided by MolDock algorithm, high affinity compound against MDM2 was retrieved. Patch Dock supervised Protein-Protein interactions were established between MDM2 and ligand (query and similar) bound and free states of p53. Compounds with PubCid 68870345, 77819398, 71132874, and 11952782 respectively structurally similar to Nutlin3A, RG7112, Mi219 and TDP 665759 demonstrated higher affinity to MDM2 in comparison to their parent compounds. Evident from the protein-protein interaction studies, all the similar compounds except for 77819398 (similar to RG 7112) showed appreciable inhibitory potential. Of particular relevance, compound 68870345 akin to Nutlin 3A had highest inhibitory potential that respectively showed 1.3, 1.2, 1.16 and 1.26 folds higher inhibitory potential than Nutilin 3A, MI 219, RG 7112 and TDP 1665759. Compound 68870345 was further mapped for structure based pharamacophoric features. In the study, we report Cis-imidazoline derivative compound; Pubcid: 68870345 to have highest inhibitory potential in blocking MDM2-p53 interactions hitherto discovered.

Extraction of Ginseng Saponins in Supercritical Ammonia Fluids (초임계 암모니아 유체에서의 인삼 사포닌 추출)

  • O, Sang O;Seok, Hwi Yeong
    • Journal of the Korean Chemical Society
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    • v.34 no.6
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    • pp.663-672
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    • 1990
  • The extraction of ginseng saponins with near critical or supercritical ammonia(SCF-NH$_3$) was carried out at 80$^{\circ}C$-160$^{\circ}C$ and ammonia densities of 339.8-525 $mg/cm^3$. In order to evaluate brownish color of white ginseng extracts, a spetrophotometric method was applied in ultraviolet and visible range. The extractibilities of ginseonoside $Rb_1$, -$Rb_2$, -Rc, -Rd, -Re, -Rf, $-Rg_1$, and $-Rg_2$ were determined by high performance liquid choromatography. The best extractability was 7.36% at 133$^{\circ}C$ and 403 $\pm$ 24.605 $mg/cm^3$. In the case of the high extraction temperature, it is thought that extraction times can be reduced and the selectivity of protopanaxatriol can be increased. The brownish color of extracts is affected by temperature and extractability. When extraction temperature is between 132$^{\circ}C$ and 140$^{\circ}C$, it is shown that the range is the retrograde region where extractablility decrease with increasing temperature.

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Changes of Ginsenosides and Color from Black Ginsengs Prepared by Steaming-Drying Cycles (흑삼 제조과정 중 증포 횟수에 따른 색상 및 진세노사이드 함량 변화)

  • Nam, Ki-Yeul;Lee, Nu-Ri;Moon, Byung-Doo;Song, Gyu-Yong;Shin, Ho-Sang;Choi, Jae-Eul
    • Korean Journal of Medicinal Crop Science
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    • v.20 no.1
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    • pp.27-35
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    • 2012
  • This study was conducted to investigate changes in composition of ginsenosides and color of processed ginsengs prepared by different steaming-drying times. Processed ginsengs were prepared from white ginseng with skin by 9-time repeated steaming at $96^{\circ}C$ for 3 hours and followed by hot air-drying at $50^{\circ}C$ for 24 hours. As the times of steaming processes increased, lightness (L value) decreased and redness (a value) increased in color of ginseng powders. Crude saponin contents and ginsenosides compositions in processed ginsengs prepared by different steaming-drying times were investigated using the HPLC method, respecively. Crude saponin contents according to increasing steaming-drying times decreased in some degree. In the case of major ginsenosides, the contents of $Rb_1$, $Rb_2$, Rc, Rd, Rf, Re, $RG_1$, Re were decreased with increase in steamimg times, but those of $Rh_1$, $Rg_3$, $Rk_1$ were increased after especially 3 times of steaming processes. Interestingly, in black ginseng were prepared by 9 times steaming processes, the content of ginsenoside $Rg_3$ was 8.20 mg/g, approximately 18 times higher than that (0.46 mg/g) in red ginseng. In addition, the ratio of the protopanaxadiol group and protopanaxatiol group (PD/PT) were increased from 1.9 to 8.4 due to increasing times of steamming process.

Changes in the Functional Components of Lactobacillus acidophilus-Fermented Red Ginseng Extract and Its Application to Fresh Cheese Production (Lactobacillus acidophilus로 발효한 홍삼 농축액의 기능성 성분 변화 및 이를 이용한 신선치즈 제조)

  • Park, Jong-Hyuk;Moon, Hye-Jung;Oh, Jeon-Hui;Lee, Joo-Hee;Jung, Hoo-Kil;Choi, Kyung-Min;Cha, Jeong-Dan;Lim, Ji-Ye;Han, Su-Beom;Lee, Tae-Bum;Lee, Min-Jung;Choi, Hye-Ran
    • Journal of Dairy Science and Biotechnology
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    • v.32 no.1
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    • pp.47-53
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    • 2014
  • In this study, our aim was to investigate the changes in ginsenosides and polyphenols in red ginseng extract fermented by Lactobacillus acidophilus and to manufacture fresh cheese using fermented red ginseng extract. Red ginseng extract (3%, w/v) was fermented by L. acidophilus for 24 h. On performing lactic acid bacteria counts, we determined that L. acidophilus reached its maximum growth phase after 16 h; this was followed by decrease in growth. During fermentation, the levels of ginsenosides Rg3 (20S) and Rg3 (20R) as well as protopanaxadiol (20R), F1, and compound K increased, while those of s Rb2, Rd, Rf, and Rg1 decreased. The pH, titratable acidity, and viable cell counts in fresh cheese prepared using fermented red ginseng extract were measured during the storage period. The pH decreased over time, while titratable acidity and viable cell counts increased with increase in the duration of the storage period. Sensory tests showed that the overall sensory properties of fresh cheese prepared using 1% fermented red ginseng extract were similar to those of the control groups. This result suggests that L. acidophilus-fermented red ginseng has potential for development as a new bioactive material.

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Improved human hematopoietic reconstitution in HepaRG co-transplanted humanized NSG mice

  • Kim, Jin;Ryu, Bokyeong;Kim, Ukjin;Kim, Chang-Hwan;Hur, Gyeung-Haeng;Kim, C-Yoon;Park, Jae-Hak
    • BMB Reports
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    • v.53 no.9
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    • pp.466-471
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    • 2020
  • Several humanized mouse models are being used to study humanspecific immune responses and diseases. However, the pivotal needs of fetal tissues for the humanized mice model have been huddled because of the demand for ethical and medical approval. Thus, we have verified the hematopoietic and immunomodulatory function of HepaRG and developed a new and easy humanized mouse model to replace the use of fetal liver tissue. HepaRG co-transplanted Hu-NSG mice significantly increased CD45+ lymphocytes and CD19+ B cells and CD3+ T cells than normal Hu-NSG, suggesting enhanced reconstitution of the human immune system. These results have improved the applicability of humanized mice by developing new models easily accessible.

Anti-inflammatory Effect of Red Ginseng through Regulation of MAPK in Lipopolysaccharide-stimulated RAW264.7 (Lipopolysaccharide로 유도된 RAW264.7 세포에서 MAPK에 의한 홍삼추출물의 항염증 효과)

  • Shin, Ji-Su;Kim, Jong-Myoung;An, Won-Gun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.3
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    • pp.293-300
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    • 2012
  • Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important inflammatory mediators implicated in pathogenesis of inflammation and certain types of human cancers. The present study was designed to determine whether Red Ginseng (RG) could modulate $I{\kappa}B$-kinase, iNOS and COX-2 gene expression and immune responses in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). RG extract suppressed the expression of LPS-induced $I{\kappa}B$, iNOS, COX-2, and immune responses in a dose-dependent manner. It also showed an anti-inflammatory effect by inhibiting NF-${\kappa}B$ immune response induced by LPS treatment. Inhibitory effect of RG on LPS-induced inflammation was mediated by suppressed phosphorylation of ERK, JNK and p38 through the regulation of the mitogen-activated protein kinase (MAPK) pathway leading to a decreased production of NO, iNOS, COX-2 and NF-${\kappa}B$. The results implied the role of RG as an inflammation regulator and its possible application for curing inflammatory diseases.

Supplementary effect of the rice germ oil on Lipid Metabolism in Diabetic KK Mice (쌀눈기름의 급여가 KK 당뇨 마우스의 지질대사에 미치는 영향)

  • 이성현;전혜경;장순옥;이연숙
    • The Korean Journal of Community Living Science
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    • v.14 no.3
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    • pp.59-65
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    • 2003
  • This study was carried out to investigate the supplementary effects of the rice germ oil compared with soy bean oil on lipid metabolism of non-insulin dependent diabetic mice. Forty diabetic KK mice were fed two kinds of experimental diets with 20% lipid from soy bean oil as a control(CO) and rice germ oil(RG) for 8 weeks, respectively. Diet intake, body weight, organs weights and lipids levels of serum, liver and feces were measured. There was no significant difference in food and water intake, body weight gain and organs weights between experimental groups. But the concentrations of serum total cholesterol and LDL-cholesterol were lower in RG group than in CO group. The hepatic total lipid and total cholesterol levels of RG group were significantly lower than those of CO group. The contents of total lipid, triglyceride and total cholesterol excreted in feces of RG group were higher than those of CO group. These results suggested that rice germ oil can reduce serum total cholesterol and LDL-cholesterol and hepatic total lipid concentration of non-insulin dependent diabetic mice compared with soybean oil due to increasing fecal lipid excretion. But we need to investigate the hypolipidemic effect of this oil by supplementary level and period.

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The effect of ginsenosides on depression in preclinical studies: A systematic review and meta-analysis

  • Kim, Yunna;Cho, Seung-Hun
    • Journal of Ginseng Research
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    • v.45 no.3
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    • pp.420-432
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    • 2021
  • Background: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. Methods: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. Results: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. Conclusion: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.

Neuroprotective effects of Rg3-enriched Korean Red Ginseng on alcohol-induced apoptosis in PC12 Cells (PC12 세포에서 알코올 유발성 세포 사멸에 대한 Rg3 풍부 고려 홍삼의 신경세포 보호 효과)

  • Choi, Na-Eun;Ryu, Jin-Hyeob;Lee, Dong-Ha;Cho, Hyun-Jeong
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.18 no.12
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    • pp.521-528
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    • 2017
  • Excessive alcohol consumption is one of the leading causes of many neurological diseases, such as dementia and Alzheimer's disease, and many efforts are under way to solve them. Red ginseng is known to enhance neuronal survival, inhibit apoptosis, and promote nerve regeneration of nerve cells. This study examined whether Rg3-enriched Korean red ginseng extract (KRG) inhibits the apoptosis of PC12 cells caused by alcohol-induced neurotoxicity and how KRG regulates several factors related to the caspase mediated pathway. In this way, the cell survival rate and apoptosis rate of PC12 cells were measured using an EZ-Cytox cell viability assay kit and flow cytometry, respectively. The expression of the apoptosis-related proteins (Bcl-2, Bid, Bax and caspase-3) were analyzed by western blotting, and the significance of the measured results was confirmed using the ANOVA method. As a result, KRG increased the expression of Bcl-2; inhibited the expression of Bid, Bax, and caspase-3; and inhibited the apoptosis of alcohol-induced PC12 cells. These results mean that the KRG-induced increase in Bcl-2 expression and down-regulation of Bid and Bax expression down-regulate caspase-3 expression, which in turn inhibits the mitochondrial apoptotic pathways. This study suggests that KRG is worth developing as a neuroprotective agent candidate.

A CMOS Wide-Bandwidth Serial-Data Transmitter for Video Data Transmission (영상신호 전송용 CMOS 광대역 시리얼 데이터 송신기)

  • Lee, Kyungmin;Park, Sung Min
    • Journal of the Institute of Electronics and Information Engineers
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    • v.54 no.4
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    • pp.25-31
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    • 2017
  • This paper presents a 270/540/750/1500-Mb/s serial-data transmitter realized in a $0.13-{\mu}m$ CMOS technology for the applications of video data transmission. A low-cost RG-58 copper cable(5C-HFBT-RG6T) is exploited as a transmission medium connected to a single BNC connector, which shows cable loss 45 dB in maximum at 1.5 GHz. RLGC modeling provides an equivalent circuit for SPICE simulations of which characteristics are very similar to the measured cable loss. The loss can be compensated by pre-emphasis at transmitter and equalization at receiver if needed. Measurements of the proposed transmitter chip demonstrate the operations of 270-Mb/s, 540-Mb/s, 750-Mb/s and 1.5-Gb/s, and provide the output voltage levels of $370mV_{pp}$ at 1.5 Gb/s even with the pre-emphasis turned-off. The total power consumption is 104 mW from 1.2/3.3-V supplies and the chip occupies the area of $1.65{\times}0.9mm^2$.