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Bioactivity-guided isolation of ginsenosides from Korean Red Ginseng with cytotoxic activity against human lung adenocarcinoma cells

  • Yu, Jae Sik;Roh, Hyun-Soo;Baek, Kwan-Hyuck;Lee, Seul;Kim, Sil;So, Hae Min;Moon, Eunjung;Pang, Changhyun;Jang, Tae Su;Kim, Ki Hyun
    • Journal of Ginseng Research
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    • v.42 no.4
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    • pp.562-570
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    • 2018
  • Background: Lung cancer is the leading cause of cancer-related death worldwide. In this study, we used a bioactivity-guided isolation technique to identify constituents of Korean Red Ginseng (KRG) with antiproliferative activity against human lung adenocarcinoma cells. Methods: Bioactivity-guided fractionation and preparative/semipreparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) after treatment with KRG extract fractions and constituents thereof were assessed using the water-soluble tetrazolium salt (WST-1) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. Caspase activation was assessed by detecting its surrogate marker, cleaved poly adenosine diphosphate (ADP-ribose) polymerase, using an immunoblot assay. The expression and subcellular localization of apoptosis-inducing factor were assessed using immunoblotting and immunofluorescence, respectively. Results and conclusion: Bioactivity-guided fractionation of the KRG extract revealed that its ethyl acetate-soluble fraction exerts significant cytotoxic activity against all human lung cancer cell lines tested by inducing apoptosis. Chemical investigation of the ethyl acetatesoluble fraction led to the isolation of six ginsenosides, including ginsenoside Rb1 (1), ginsenoside Rb2 (2), ginsenoside Rc (3), ginsenoside Rd (4), ginsenoside Rg1 (5), and ginsenoside Rg3 (6). Among the isolated ginsenosides, ginsenoside Rg3 exhibited the most cytotoxic activity against all human lung cancer cell lines examined, with $IC_{50}$ values ranging from $161.1{\mu}M$ to $264.6{\mu}M$. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspase-independent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.

Compatibility effects of ginseng and Ligustrum lucidum Ait herb pair on hematopoietic recovery in mice with cyclophosphamide-induced myelosuppression and its material basis

  • Han, Jiahong;Dai, Min;Zhao, Yan;Cai, Enbo;Zhang, Lianxue;Jia, Xiaohuan;Sun, Nian;Fei, Xuan;Shu, Hui
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.291-299
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    • 2020
  • Background: Ginseng (G) and Ligustrum lucidum Ait (LLA) are core traditional Chinese medicines in treating myelosuppression formula. The present study was designed to profile effect of G and LLA herb pair (G-LLA) on myelosuppressed mice. Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide (Cy). Hematopoietic function of bone marrow was measured by hemopoietic progenitor cell culture and peripheral blood count, and serum hemopoietic factors were tested by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. HPLC was used to measure 20 potential chemical components related to myelosuppression, including ginsenoside Rg1, Re, Rb1, Rc, Rb2, Rb3, Rd, Rk3, Rh4, 20 (S)-Rg3, 20 (R)-Rg3, Rk1, Rg5, salidroside, and so on. Results: G, LLA, and G-LLA improved the amount of peripheral blood cells and bone marrow cells of myelosuppressed mice (P < 0.01). They significantly increased the colony quantity of colony-forming unit-granulocyte macrophage, burst-forming unit-erythroid, colony-forming unit-erythroid, and colony-forming unit-megakaryocyte and amount of G2/M and S phase cells (P < 0.01). They also significantly decreased the amount of hematopoiesis-related cytokines (P < 0.01). The content of chemical components in G-LLA changed, and the change of rare saponin was the most obvious. Conclusion: These results show that G-LLA herb pair might produce synergistic or complementary compatibility effects on bone marrow suppression after chemotherapy. It suggests that the substance basis of G-LLA for treating bone marrow suppression may be effective chemical components.

SEM EVALUATION OF THE PREPARED ROOT CANALS BY HAND AND Ni-Ti ROTARY ROOT CANAL INSTRUMENTS (Hand & rotary root canal instrument의 근관내 삭제 형태에 관한 전자현미경적 비교)

  • Oh, Tae-Seok;Park, Jeong-Won
    • Restorative Dentistry and Endodontics
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    • v.23 no.1
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    • pp.477-486
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    • 1998
  • Recently the development of rotary instrument makes it possible that in root canal treatment operator saves much more time, maintans original curved canal shape and easily prepares continuous tapered root canal. The purpose of this experiment was to examine the smoothness of the internal surface of prepared root canal and the effectiveness of debridement in prepared root canal by SEM for the comparison of hand and Ni-Ti rotary instrument. 25 extracted human teeth were access opened and # 10 K-type file was introduced into canal until it was appeared at the apical foramen. The working length was established by subtracting 0.5mm from this measurement. Group 1. The root canal preparation was done to # 30 with working length and then step-back until # 45 with K-Flexofile (Maillefer, Swiss). Group 2. Root canal preparation was done by Naviflex Ni-Ti file (Brasseler, USA) as the same technique with group 1. Group 3. Canal was prepared by Profile .04 (Maillefer, Swiss) taper until #30. Group 4. With use of Quantec (Tycom, USA) root canal was prepared from file number 1 to 8. In group 1 and 2, the root canal irrigant was NaOCl and the other groups, NaOCl and RC-prep (Premine Dental Products, USA) was used. The prepared teeth were notched with high-speed bur as bucco-lingual direction and fractured with chisel and mallet, then examined with SEM. Group 1 showed smooth internal surface. There were scratches mainly to the axial direction. Group 2 showed similar characteristics to those in group 1. Group 3 showed more smoother and linear cutting surface with bised scratches. Group 4 has the almost same characteristics group 3 and there was no difference in the file design. Ni-Ti rotary root canal instrument prepare the dentinal wall more smoother than hand instrument. The effectiveness of debridement was not fully affected by file design. The isthmus area and accessory canals of the root canal system were not prepared in any group. According to the result, hand and rotary type instrumentation techniques were effective in removal of major amount of tissue from root canal but it was not complete. In the direction of cutting movement there was difference between them.

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Clinical Studies on Locally Invasive Thyroid Cancer (국소침범한 갑상선암의 임상적 고찰)

  • Kim Young-Min;Lee Chang-Yun;Yang Kyung-Hun;Rho Young-Soo;Park Young-Min;Lim Hyun-Jun
    • Korean Journal of Head & Neck Oncology
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    • v.14 no.2
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    • pp.236-243
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    • 1998
  • Objectives: Local invasion of the thyroid cancer that is invasion of the upper aerodigestive tract, neurovascular structures of the neck and superior mediastinum, is infrequent and comprises of 1-16% of well-differentiated thyroid cancer. However the proximity of the thyroid gland to these structures provides the means for an invasive cancer to gain ready access into theses structures and when invasion occurs, it is the source of significant morbidity and mortality. So locally invasive thyroid cancer should be removed as much as possible, but still much debates have been exist whether the surgical method should be radical or conservative. This study was desinged to evaluate the clinical characteristics and the surgical treatment of the locally invasive thyroid cancer. Material and Methods: At the department of otorhinolaryngology of Hallym university, 10 patients diagnosed as locally invasive thyroid cancer among the 81 patients treated for thyroid cancer between 1991 to 1997 were retrospectively evaluated. Results: Of the 10 patients, 3 patients had histories of previous surgical treatment with or without radiation or radioactive iodine therapy. The site of invasion of thyroid cancer were trachea(7 cases), recurrent laryngeal nerve(5 cases), mediastinal node(5 cases), esophagus(3cases), larynx(3cases), carotid artery(3 cases), pharynx(l case), and other sites(4 cases). The operation techniques included 1 partial laryngectomy and 1 partial cricoid resection, 2 shavings and 3 window resections of the trachea, 1 sleeve resection of the trachea with end-to-end anastomosis and 1 cricotracheoplasty for tracheal invasion, 2 shavings and 1 partial esophagectomies for esophageal invasion, and 1 wall shaving and 2 partial resections with $Gortex^{\circledR}$ tube reconstruction for carotid artery invasion, and so on. Conclusions: These data and review of literature suggest that the surgical method should be perfomed on the basis of individual condition and complete removal of all gross tumor with preservation of vital structures whenever possible will offer a good result.

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Protective Effects of Chaenomeles sinensis Koehne Extract on Ethanol-induced Liver Damage in Rat (에탄올에 의해 유발된 간독성에 대한 모과 추출물의 보호효과)

  • Lee, Yu-Mi;Lee, Jae-Joon;Shin, Hyoung-Duck;Lee, Myung-Yul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.10
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    • pp.1336-1342
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    • 2006
  • This study was performed to investigate the effect of ethanol extract of Chaenomeles sinensis Koehne (CS) on alcohol-induced liver damage in rats. Male Sprague-Dawley rats weighing $135{\pm}10g$ were divided into 6 groups for 4 weeks; normal group (ND), alcohol (35%, 10 mL/kg/day) treated group (ET), CS ethanol extract 200 mg/kg/day treated group (ND-CSL), CS ethanol extract 400 mg/kg/day treated group (ND-CSH), CS ethanol extract 200 mg/kg/day and alcohol treated group (ET-CSL), and CS ethanol extract 400 mg/kg/day and alcohol treated group (ET-CSH). The body weight gain and food efficiency ratio were no differences between ND and ET. There were increases in the activities of serum alanine aminotransferase (ALT), asparate aminotransferase (AST), and alkaline phosphatase (ALP) in ET. On the other hand, the administration of CS decreased ALT, AST and ALP activities in serum. It was also observed that the hepatic activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) increased by alcohol treatment were also markedly decreased in the CS administered groups as compared with ET. The activities of hepatic SOD, catalase, GSH-Px and XO were riot significantly different among the normal diet groups. Contents of thiobarbituric acid reactive substances (TBARS) were increased by the administration of alcohol, on the other hand, the administration of CS reduced TBARS value in the liver. In addition, the content of glutathione (GSH) in the liver was decreased by alcohol administration, however, GSH increased after administering CS. In conclusion, the administration of alcohol develops the hyperoxidation of liver lipids through tile increase in enzymes activity related to the lipid peroxiation, however, it was decreased after administring CS. Thus, CS may have a possible protective effect on ethanol-induced hepatotoxicity in rat liver.

Development of Measuring Technique for Milk Composition by Using Visible-Near Infrared Spectroscopy (가시광선-근적외선 분광법을 이용한 유성분 측정 기술 개발)

  • Choi, Chang-Hyun;Yun, Hyun-Woong;Kim, Yong-Joo
    • Food Science and Preservation
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    • v.19 no.1
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    • pp.95-103
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    • 2012
  • The objective of this study was to develop models for the predict of the milk properties (fat, protein, SNF, lactose, MUN) of unhomogenized milk using the visible and near-infrared (NIR) spectroscopic technique. A total of 180 milk samples were collected from dairy farms. To determine optimal measurement temperature, the temperatures of the milk samples were kept at three levels ($5^{\circ}C$, $20^{\circ}C$, and $40^{\circ}C$). A spectrophotometer was used to measure the reflectance spectra of the milk samples. Multilinear-regression (MLR) models with stepwise method were developed for the selection of the optimal wavelength. The preprocessing methods were used to minimize the spectroscopic noise, and the partial-least-square (PLS) models were developed to prediction of the milk properties of the unhomogenized milk. The PLS results showed that there was a good correlation between the predicted and measured milk properties of the samples at $40^{\circ}C$ and at 400~2,500 nm. The optimal-wavelength range of fat and protein were 1,600~1,800 nm, and normalization improved the prediction performance. The SNF and lactose were optimized at 1,600~1,900 nm, and the MUN at 600~800 nm. The best preprocessing method for SNF, lactose, and MUN turned out to be smoothing, MSC, and second derivative. The Correlation coefficients between the predicted and measured fat, protein, SNF, lactose, and MUN were 0.98, 0.90, 0.82, 0.75, and 0.61, respectively. The study results indicate that the models can be used to assess milk quality.

Evaluation of the Minimum Shear Reinforcement Ratio of Reinforced Concrete Members (철근콘크리트 부재의 최소전단보강근비의 평가)

  • Lee Jung-Yoon;Yoon Sung-Hyun
    • Journal of the Korea Concrete Institute
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    • v.16 no.1 s.79
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    • pp.43-53
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    • 2004
  • The current Korean Concrete Design Code(KCI Code) requires the minimum and maximum content of shear s in order to prevent brittle and noneconomic design. However, the required content of the steel reinforcement In KCI Code is quite different to those of the other design codes such as fib-code, Canadian Code, and Japanese Code. Furthermore, since the evaluation equations of the minimum and maximum shear reinforcement for the current KCI Code were based on the experimental results, the equations can not be used for the RC members beyond the experimental application limits. The concrete tensile strength, shear stress, crack inclination, strain perpendicular to the crack, and shear span ratio are strongly related to the lower and upper limits of shear reinforcement. In this research, an evaluation equation for the minimum content of shear reinforcement is theoretical proposed from the Wavier's three principals of the mechanics of materials.

A Study of variables Related to Nursing Productivity (간호생산성에 관한 연구: 관련변수의 검증을 중심으로)

  • 박광옥
    • Journal of Korean Academy of Nursing
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    • v.24 no.4
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    • pp.584-596
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    • 1994
  • The objective of the study is to explore the relationships between the variables of nursing productivity on the framework of system del in the tertiary university based care hospital in Korea. Productivity is basically defined as the relation-ship between inputs and outputs. Under the proposition that the nursing unit is a system that produces nursing care output using personal and material resources through the nursing intervention and nursing care management. And this major conception of nursing productivity system comproises input, process and output and feed-back. These categorized variables are essential parts to produce desirable and meaningful out-put. While nursing personnel from head nurse to staff nurses cooperate with each other, the head nurse directs her subordinates to achieve the goal of nursing care unit. In this procedure, the head nurse uses the leadership of authority and benevolence. Meantime nursing productivity will be greatly influenced by environment and surrounding organizational structures, and by also the operational objectives, the policy and standards of procedures. For the study of nursing productivity one sample hospital with 15 general nursing care units was selected. Research data were collected for 3 weeks from May 31 to June 20 in 1993. Input variables were measured in terms of both the served and the server. And patient classification scores were measured drily by degree of nursing care needs that indicated patent case-mix. And also nurses' educational period for profession and clinical experience and the score of nurses' personality were measured as producer input variables by the questionnaires. The process varialbes act necessarily on leading input resources and result in desirable nursing outputs. Thus the head nurse's leadership perceived by her followers is defined as process variable. The output variables were defined as length of stay, average nursing care hours per patient a day the score of quality of nursing care, the score of patient satisfaction, the score of nurse's job satis-faction. The nursing unit was the basis of analysis, and various statistical analyses were used : Reliability analysis(Cronbach's alpha) for 5 measurement tools and Pearson-correlation analysis, multiple regression analysis, and canonical correlation analysis for the test of the relationship among the variables. The results were as follows : 1. Significant positive relationship between the score of patient classification and length of stay was found(r=.6095, p.008). 2. Regression coefficient between the score of patient classification and length of stay was significant (β=.6245, p=.0128), and variance explained was 39%. 3. Significant positive relationship between nurses’ educational period and length of stay was found(r=-.4546, p=.044). 5. Regression coefficient between nurses' educational period and the score of quality of nursing care was significant (β=.5600, p=.029), and variance explained was 31.4%. 6. Significant positive relationship between the score of head nurse's leadership of authoritic characteristics and the length of stay was found (r=.5869, p=.011). 7. Significant negative relationship between the score of head nurse's leadership of benevolent characteristics and average nursing care hours was found(r=-.4578, p=.043). 8. Regression coefficient between the score of head nurse's leadership of benevolent characteristics and average nursing care hours was significant(β=-.6912, p=.0043), variance explained was 47.8%. 9. Significant positive relationship between the score of the head nurse's leadership of benevolent characteristics and the score of nurses' job satis-faction was found(r=.4499, p=050). 10. A significant canonical correlation was found between the group of the independent variables consisted of the score of the nurses' personality, the score of the head nurse's leadership of authoritic characteristics and the group of the dependent variables consisted of the length of stay, average nursing care hours(Rc²=.4771, p=.041). Through these results, the assumed relationships between input variables, process variable, output variables were partly supported. In addition it is also considered necessary that-further study on the relationships between nurses' personality and nurses' educational period, between nurses' clinical experience including skill level and output variables in many research samples should be made.

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Antimicrobial Effect of Red Ginseng Against Major Food Poisoning Microorganisms Including Staphylococcus aureus (황색포도상구균을 포함한 식중독 미생물들에 대한 홍삼의 항균효과)

  • Kwak, Yi-Seong;Jung, Myung-Gyun;Jang, Kyoung-Hwa;Han, Min-Woo;Yu, Byeung-Il
    • Journal of Food Hygiene and Safety
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    • v.35 no.4
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    • pp.382-390
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    • 2020
  • This study was carried out to evaluate the antimicrobial effect of red ginseng (Panax ginseng C.A. Meyer) against several foodborne pathogens including Staphylococcus aureus, Escherichia coli, Candida albicans and Aspergillus niger. The antimicrobial effect was determined by agar diffusion method using red ginseng extract, crude saponin and non-water-soluble fractions. Red ginseng extract showed antimicrobial effect against S. aureus, but not C. albicans or A. niger. The extract showed anti-bacterial activity at concentration above 30% against S. aureus, which cause both food poisoning and atophic dermatitis. Crude saponin showed antibacterial activity above 7.5% against the bacterium. However, the ginsenosides purified from crude saponin showed no antimicrobial activities at 100-200 ㎍/mL. To investigate the mode of growth inhibition, red ginseng extract and crude saponin were added to 0.85% NaCl solution containing S. aureus and then incubated at 35℃ for 12 h. The results showed that viable cells were rapidly reduced in above 10% concentration of red ginseng extract and above 2% of crude saponin, respectively. However, the crude saponin and red ginseng extract did not inhibit the bacterial cells completely at those same concentrations. On the other hand, whereas all non-water-soluble fractions showed inhibition zones above 10 mm against S. aureus, they showed no inhibition effects against E. coli, C. albicans or A. niger. The methanol fraction-1 (MF-1) showed the highest antibacterial activity against S. aureus, and the MIC (minimal inhibitory concentration) was 0.625 mg/mL. These results suggest that red ginseng extract, crude saponin and non-water-soluble fractions show selective antibacterial activity against S. aureus, and non-water-soluble fractions might be used as natural antibacterial agents.

EFFECTS OF GINSENG COMPONENTS ON RODENTICIDE VACOR-INDUCED DIABETES MELLITUS IN RATS (인삼성분이 살서제(Vacor)로 유발시킨 쥐의 당뇨에 미치는 영향)

  • Lee Min-wha;Lee Tai-hee;Ahn Bong-whan;Park Byung-ju;Yang Sung-yeul
    • Proceedings of the Ginseng society Conference
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    • 1984.09a
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    • pp.83-88
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    • 1984
  • It is now well established that the rodenticide Vacor (N-3-pyridyl-mehtyl-N'-p-nitropheny-lurea) causes a hyperglycemia in human and rats. It is also reported that there are some components (DPG-3) in ginseng radix which cause hypoglycemic effect on alloxan diabetic mice. In the present study, attempts were made to demonstrate in Vacor-poisoned rats the hypo-glycemic activity of red ginseng component(RGC), which was extracted by Kimura's DPG-3 extraction procedure and found to be effective for lowering a hyperglycemia in alloxan-diabetic rats. Vacor in a dose of $LD_{50}$ (10mg/kg) produced a glucose intolerance with a paradoxical moderate increase in blood immunoreactive insulin and derangement in glucose metabolism of epididymal adipocytes in rats. Although RGC (20mg/kg, i.p.) did not exert any significant influence on a hyperglycemia induced by large lethal doses (25mg/kg) of Vacor ingestion, it improved the LDso Vacor-induced glucose intolerance and caused a further increase in blood insulin levels in Vacor-poisoned rats. The administration of RGC (20mg/kg, i.p.) normalized Vacor-induced depression of glucose metabolism and lipogenesis in the epididymal adipocytes with an improvement of reduced responses to insulin of adipocytes from Vacor-poisoned rats. These results suggest that some red ginsneng components contained in RGC fraction normalize the depressed peripheral glucose unitlization and insulin response and eventually lead to an improvement of abnormal glucose tolerance developed in rats poisoned with small doses of Vacor.

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