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Anti-cancer Properties and Relevant Mechanisms of Cordycepin, an Active Ingredient of the Insect Fungus Cordyceps spp., (동충하초 유래 cordycepin의 항암 활성 기전 최근 연구 동향)

  • Jeong, Jin-Woo;Choi, Yung Hyun
    • Journal of Life Science
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    • v.25 no.5
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    • pp.607-614
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    • 2015
  • Cancers are the largest cause of mortality and morbidity all over the world. Cordycepin, an adenosine analog, is a major functional component of the Cordyceps species, which has been widely used in traditional Oriental medicine. Over the last decade, this compound has been reported to possess many pharmacological properties, such as an ability to enhance immune function, as well as anti-inflammatory, antioxidant and anti-cancer effects. Recently, numerous studies have reported interesting properties of cordycepin as a chemopreventive agent as well. There is an accumulating body of experimental evidences suggesting that cordycepin impedes cancer progression by promoting apoptosis, inducing cell cycle arrest, modulating intracellular signaling pathways, and inhibiting invasion and metastasis of cancer cells. In many cancer cell lines, cordycepin inhibits growth and cell cycle progression by inducing arrest of the G2/M phase, resulting from the inhibition of retinoblastoma protein phosphorylation and induction of cyclin-dependent kinase inhibitors. To induce apoptosis, cordycepin activates the extrinsic and intrinsic pathways, which promotes reactive oxygen species generation and the downstream activation of kinase cascades. Cordycepin also can activate alternative pathways to cell death such autophagy. In addition, cordycepin can inhibit the pro-metastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the nuclear factor-kappa B and activated protein-1 signaling pathways. In this review, we summarized the variety of action mechanisms by which cordycepin may mediate chemopreventive effects on cancer and discussed the potential of this natural product as a promising therapeutic inhibitor of cancer development.

Effect of Korean Traditional Teas on Plasma and Hepatic Lipid Levels in Lead-Administered Rats (한국전통차가 납투여된 흰쥐의 혈장과 간조직 중 지질농도에 미치는 영향)

  • 김덕진;조수열;김명주
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.2
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    • pp.263-268
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    • 2003
  • This study was designed to test the effect of Korean traditional teas on lipid levels in lead (Pb)-administered rats. Male rats were divided into normal, Pb-control (rb-Con) and Pb-water extract of traditional teas (green tea: GWE, persimmon leaf: PWE, safflower seed: SWE, Solomon's seal: SSWE) groups. Pb intoxication was induced by administration lead acetate (25 mg/kg. BW, oral) weekly. The extract was administered based on 1.26 g of raw traditional tea/g BWday for 4 weeks. Net weight gain and feed intake were significantly lower in the Pb-Con group than in the normal group, whereas they were tended to increase by traditional teas supplements. Both Plasma and hepatic total cholesterol and triglyceride concentration were lower in the traditional teas supplemented groups compared to the Pb-Con group. Plasma VLDL-cholesterol and LDL-cholesterol levels were significantly increased by Pb ad-ministration, whereas HDL-cholesterol concentration was significantly lower in the Pb-Con group than in the normal group. However, water extracts of green tea, persimmon leaf, safflower seed and solomon's seal supplementation improved changes of the plasma lipoprotein-cholesterol levels in Pb administered rats.

Effect of Water Extract of Green tea, Persimmon Leaf and Safflower Seed on Heme Synthesis and Erythrocyte Antioxidant Enzyme Activities in Lead-Administered Rats (납투여한 흰쥐의 헴합성과 적혈구 중의 항산화효소 활성에 미치는 녹차, 감잎, 홍화 열수추출물의 영향)

  • 김명주;조수열;장주연;박지윤;박은미;이미경;김덕진
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.2
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    • pp.191-196
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    • 2003
  • This study was performed to investigate the effect of water extract of green tea (GT), persimmon leaf (PL) and safflower seed (SS) on heme synthesis and erythrocyte antioxidant enzyme activities in lead (Pb)-administered rats. Male rats were divided into five groups. a normal, Pb-control (Pb-Con), Pb-GT, Pb-PL and Pb-55 groups with ten rats per group. Pb (25 mg/kg. BW) was orally administerd once a day for 4 weeks. The extract of GT, PL and 55 were administered based on 1.26 g of raw traditional tea/kg BW/day. Blood hematocrit, homoglobin level and red blood cell counts were significantly lower in rb-Con group than in normal group. However, the supplementation of GT, PL and 55 were effective to improve the hematological parameters. Plasma AST and ALT activities were significantly lower in Pb-GT, Pb-PL, Pb-SS groups than in Pb-Con group. The $\delta$ -amino-levulinic acid dehydratase (ALAD) activity of blood and liver were significantly lowered in Pb-Con group com-pared to those of the normal group. The ALAD activity in Pb administered rats was recovered to tile normal level by the water extract of GT, PL and 55 supplementation. Erythrocyte superoxide dismutase and catalse activities were significantly higher in Pb-Con group than in normal group, whereas glutathione peroxidase activity was lowered in Pb administered rats. The extract of GT, PL and SS supplement attenuated changes of these erythrocyte antioxidant enzyme activities by Pb intoxication.

Effects of Sophorae Radix Extracts on the Expression ofcell cycle regulatory porteins in Human Gingival Fibroblasts (고삼추출물이 치은섬유아세포의 세포주기 조절단백질 발현에 미치는 영향)

  • Kim, Heung-Sik;Kim, Hyun-A;Yu, Yong-Ouk;Kang, Tai-Hyun;Kim, Youn-Chul;Kim, Tak;Pee, Sung-Hee;You, Hyung-Keun;Shin, Hyung-Shik
    • Journal of Periodontal and Implant Science
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    • v.30 no.4
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    • pp.869-885
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    • 2000
  • Fibroblasts are major cellular components of gingiva and periodontal ligament. They regulate the healing process after surgery or injury. Recently, many natural medicines, whose advantages are less side effects and possibility of long-term use, have been studied for their capacity, their anti-bacterial and anti-inflammatory effects and regenerative potential of periodontal tissues. Sophorae radix have been traditionally used as an anti-bacterial and antiinflammatory drug in oriental medicine. The purpose of present study was to investigate the effects of Sophorae radix extract on cell cycle progression and its molecular mechanism in human gingival fibroblasts. Sophorae radix extracts($100{\mu}g/ml$) notably increased cell proliferation and cell activity in the human gingival fibroblasts as compared to non-supplemented controls. There was an increase in the S phase and a decrease in the G1 phase in $100{\mu}g/ml$ of Sophorae radix extracts group as compared to non-supplemented controls. The level of cyclin E and cdk 2 protein in test group was higher than that of control groups. But that of cyclin D, cdk 4, and cdk 6 was not distinguished from controls. The level of p53 protein in test group was lower than that of controls, whereas that of p21 was not different. The level of pRB protein in test group was higher than that of controls, whereas that of p16 was lower. These results indicate that the increase of cell proliferation by Sophorae radix extracts may be due to the increased expression of cyclin E and cdk 2, and the decreased expression of p53 and p16 in human gingival fibroblasts.

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THE IMMUNOHISTOCHEMICAL STUDY ON THE EXPRESSION OF p53 PROTEIN AND CYCLIN D1 IN ORAL SQUAMOUS CELL CARCINOMAS (구강 편평세포암종에서 p53 단백과 Cyclin D1발현에 대한 면역조직화학적 연구)

  • Kim, Jong-Yub;Kim, Kyung-Wook;Lee, Jae-Hoon;Kim, Chang-Jin
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.21 no.2
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    • pp.139-148
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    • 1999
  • Oral cancer is a common neoplasm in humans and etiologic mechanism is not well known, so treatment and evaluation of oral cancer is difficult problem. Traditional TNM classification between prognosis of tumors and classification of histopathologic differentiation has problem like lack of objectivity through operators. In molecular biology, cancer is developed by alteration of activation of oncogene and/or inactivation of tumor suppressor gene. The p53 gene, one of the tumor suppresor genes, is believed to play an important role through mutation and overexpression in the progression of human cancers. The p53 mutation is most frequent genetic disorder in humans. The Cyclin D1 has tumor suppresion activity by regulation of cell cycle. The Cyclin D1 regulate activity of Rb tumor suppresor gene by stimulation of CDK4 The purpose of this study was to observe the expression of p53 protein and Cyclin D1 in oral squamous cell carcinoma, and to get expectation of the malignancy and prognosis of oral squamous cell carcinoma. Using the 15 cases of squamous cell carcinoma and the microscopic H&E and immunohistochemical stain. We divided it into 3 groups according to the stain extent, clinical stage and histologic differentiation. The results were as follows1.In the features of immunohistochemical stain of 15 cases of squamous cell carcinoma, positive reaction of p53 was identified in 8 cases (53.3%) and positive reaction of cyclin D1 was identified in 3 cases (20%). Both positive reaction of p53 protein and Cyclin D1 was show in only one case. 2.8 of p53 positive cases were linked in 87.5% of the end stage tumor, 62.5% of neck node involvement, 87.5% of poorly and moderately histopathplogic differentiation. 3. All 3 of Cyclin D1 positive cases were linked in the end stage tumor, neck node involvement, poorly and moderately histopathologic differentiation. From above results, expression of p53 protein was identified in 53.3% of 15 cases and these results mean oral squamous cell carcinoma was drived by mutation of p53 protein. Especially, highly positive reaction of p53 protein and Cyclin D1 was identified in cases that involvement of neck lymph node and the end stage tumors and it means that the evaluation of p53 protein and Cyclin D1 was useful for evaluation of malignant tumor as specific tumor marker.

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Geochemistry and Tectonic Implications of Triassic Bojangsan Trachyte in the Southern Margin of the Imjingang Belt, Korea (임진강대 남변부 트라이아스기 보장산조면암의 지구화학과 조구조적 의미)

  • Hwang, Sang Koo;Ahn, Ung San
    • The Journal of the Petrological Society of Korea
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    • v.26 no.2
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    • pp.113-125
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    • 2017
  • We investigates geochemical and tectonic characteristics for the Triassic Bojangsan trachyte in the southern margin of the Imjingang belt. The geochemical signatures of the thracyte are characterized by enrichments of REE and HFS, and show no Nb trough, suggesting that would not experience arc magmatic processes involving continental crustal materials. The trachyte reveals within-plate setting in tectonic discrimination diagrams using immobile HFS Nb and Y elements. And the trachyte shows typical signatures of A-type volcanic rocks with high Ga abundance and is classified as A1-type volcanic rocks rich in Nb. The geochemical signatures suggest that the trachyte was produced by the differentiation of mantle-derived magmatism at the continental rift in extensional setting subsequent to a major collision during the Permo-Triassic Songrim orogeny. The results provide robust evodence to consider the Imjingang belt as an extension of the the Qinling-Dabie-Sulu belt between the North and South China blocks.

Substantial Protective Immunity Conferred by a Combination of Brucella abortus Recombinant Proteins against Brucella abortus 544 Infection in BALB/c Mice

  • Arayan, Lauren Togonon;Huy, Tran Xuan Ngoc;Reyes, Alisha Wehdnesday Bernardo;Hop, Huynh Tan;Son, Vu Hai;Min, WonGi;Lee, Hu Jang;Kim, Suk
    • Journal of Microbiology and Biotechnology
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    • v.29 no.2
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    • pp.330-338
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    • 2019
  • Chronic infection with intracellular Brucella abortus (B. abortus) in livestock remains as a major problem worldwide. Thus, the search for an ideal vaccine is still ongoing. In this study, we evaluated the protective efficacy of a combination of B. abortus recombinant proteins; superoxide dismutase (rSodC), riboflavin synthase subunit beta (rRibH), nucleoside diphosphate kinase (rNdk), 50S ribosomal protein (rL7/L12) and malate dehydrogenase (rMDH), cloned and expressed into a pMal vector system and $DH5{\alpha}$, respectively, and further purified and applied intraperitoneally into BALB/c mice. After first immunization and two boosters, mice were infected intraperitoneally (IP) with $5{\times}10^4CFU$ of virulent B. abortus 544. Spleens were harvested and bacterial loads were evaluated at two weeks post-infection. Results revealed that this combination showed significant reduction in bacterial colonization in the spleen with a log protection unit of 1.31, which is comparable to the average protection conferred by the widely used live attenuated vaccine RB51. Cytokine analysis exhibited enhancement of cell-mediated immune response as IFN-${\gamma}$ is significantly elevated while IL-10, which is considered beneficial to the pathogen's survival, was reduced compared to control group. Furthermore, both titers of IgG1 and IgG2a were significantly elevated at three and four-week time points from first immunization. In summary, our in vivo data revealed that vaccination with a combination of five different proteins conferred a heightened host response to Brucella infection through cell-mediated immunity which is desirable in the control of intracellular pathogens. Thus, this combination might be considered for further improvement as a potential candidate vaccine against Brucella infection.

Changes in Growth, Active Ingredients, and Rheological Properties of Greenhouse-cultivated Ginseng Sprout during its Growth Period (하우스에서 재배된 새싹인삼의 재배시기별 생육, 유효성분 및 물성의 변화)

  • Seong, Bong Jae;Kim, Sun Ick;Jee, Moo Geun;Lee, Hee Chul;Kwon, A Reum;Kim, Hyun Ho;Won, Jun Yeon;Lee, Ka Soon
    • Korean Journal of Medicinal Crop Science
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    • v.27 no.2
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    • pp.126-135
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    • 2019
  • Background: The ginseng ginsenosides, which have various physiological activities, are known to be more abundant in the leaves than in the roots, and the consumers' interest in ginseng sprout as a functional vegetable has been increasing. Methods and Results: The aim of this study was to investigate the effects of growth period on growth properties, active ingredients and rheology of ginseng sprouts cultivated in a non-heated greenhouse equipped with a shade net for 60 days, starting from the end of May to the middle of July. The chlorophyll content of the leaves decreased, but their length and width increased with increasing cultivation days. In particular, growth increased significantly until 40 days, but only slightly after 50 days. The stem length did not increase greatly from the 20 th to the 30 th day of cultivation, but increased significantly from the 30 th to the 40 th day, and then further increased gradually. The weight of the leaves, stems, and roots increased slightly, but not change significantly. After 40 days of cultivation, the total ginsenoside content increased by 1.07 times in the leaves and decreased by 0.80 times in the roots with increasing cultivation days. The leaf contents of ginsenosides $Rg_1$, Re, $Rb_1$, Rc, $F_3$ and $F_4$ increased with increasing cultivation days. The rheological properties of ginseng sprout showed the greatest influence on stem hardening with increasing cultivation days. Conclusions: Therefore, based on the growth characteristics, active ingredients and physical properties, 40 days after sowing was considered to be an appropriate harvesting time for ginseng sprouts.

Effect of Korea red ginseng on nonalcoholic fatty liver disease: an association of gut microbiota with liver function

  • Hong, Ji Taek;Lee, Min-Jung;Yoon, Sang Jun;Shin, Seok Pyo;Bang, Chang Seok;Baik, Gwang Ho;Kim, Dong Joon;Youn, Gi Soo;Shin, Min Jea;Ham, Young Lim;Suk, Ki Tae;Kim, Bong-Soo
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.316-324
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    • 2021
  • Background: Korea Red Ginseng (KRG) has been used as remedies with hepato-protective effects in liver-related condition. Microbiota related gut-liver axis plays key roles in the pathogenesis of chronic liver disease. We evaluated the effect of KRG on gut-liver axis in patients with nonalcoholic statohepatitis by the modulation of gut-microbiota. Methods: A total of 94 patients (KRG: 45 and placebo: 49) were prospectively randomized to receive KRG (2,000 mg/day, ginsenoside Rg1+Rb1+Rg3 4.5mg/g) or placebo during 30 days. Liver function test, cytokeraton 18, and fatigue score were measured. Gut microbiota was analyzed by MiSeq systems based on 16S rRNA genes. Results: In KRG group, the mean levels (before vs. after) of aspartate aminotransferase (53 ± 19 vs. 45 ± 23 IU/L), alanine aminotransferase (75 ± 40 vs. 64 ± 39 IU/L) and fatigue score (33 ± 13 vs. 26 ± 13) were improved (p < 0.05). In placebo group, only fatigue score (34 ± 13 vs. 31 ± 15) was ameliorated (p < 0.05). The changes of phyla were not statistically significant on both groups. In KRG group, increased abundance of Lactobacillus was related with improved alanine aminotransferase level and increased abundance of Clostridium and Intestinibacter was associated with no improvement after KRG supplementation. In placebo group, increased abundance of Lachnospiraceae could be related with aggravation of liver enzyme (p < 0.05). Conclusion: KRG effectively improved liver enzymes and fatigue score by modulating gut-microbiota in patients with fatty liver disease. Further studies are needed to understand the mechanism of improvement of nonalcoholic steatohepatitis. ClnicalTrials.gov: NCT03945123 (www.ClinicalTrials.gov).

A novel protocol for batch-separating gintonin-enriched, polysaccharide-enriched, and crude ginsenoside-containing fractions from Panax ginseng

  • Rami Lee;Han-Sung Cho;Ji-Hun Kim;Hee-Jung Cho;Sun-Hye Choi;Sung-Hee Hwang;Hyewon Rhim;Ik-Hyun Cho;Man-Hee Rhee;Do-Geun Kim;Hyoung-Chun Kim;Seung-Yeol Nah
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.366-375
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    • 2023
  • Background: Ginseng contains three active components: ginsenosides, gintonin, and polysaccharides. After the separation of 1 of the 3 ingredient fractions, other fractions are usually discarded as waste. In this study, we developed a simple and effective method, called the ginpolin protocol, to separate gintonin-enriched fraction (GEF), ginseng polysaccharide fraction (GPF), and crude ginseng saponin fraction (cGSF). Methods: Dried ginseng (1 kg) was extracted using 70% ethanol (EtOH). The extract was water fractionated to obtain a water-insoluble precipitate (GEF). The upper layer after GEF separation was precipitated with 80% EtOH for GPF preparation, and the remaining upper layer was vacuum dried to obtain cGSF. Results: The yields of GEF, GPF, and cGSF were 14.8, 54.2, and 185.3 g, respectively, from 333 g EtOH extract. We quantified the active ingredients of 3 fractions: L-arginine, galacturonic acid, ginsenosides, glucuronic acid, lysophosphatidic acid (LPA), phosphatidic acid (PA), and polyphenols. The order of the LPA, PA, and polyphenol content was GEF > cGSF > GPF. The order of L-arginine and galacturonic acid was GPF >> GEF = cGSF. Interestingly, GEF contained a high amount of ginsenoside Rb1, whereas cGSF contained more ginsenoside Rg1. GEF and cGSF, but not GPF, induced intracellular [Ca2+]i transient with antiplatelet activity. The order of antioxidant activity was GPF > GEF = cGSF. Immunological activities (related to nitric oxide production, phagocytosis, and IL-6 and TNF-α release) were, in order, GPF > GEF = cGSF. The neuroprotective ability (against reactive oxygen species) order was GEF > cGSP > GPF. Conclusion: We developed a novel ginpolin protocol to isolate 3 fractions in batches and determined that each fraction has distinct biological effects.