• Journal of Ginseng Research
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• v.39 no.3
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• pp.199-205
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• 2015

Background: Ginsenoside Rb1 (G-Rb1), the major active constituent of ginseng, improves insulin sensitivity and exerts antidiabetic effects. We tested whether the insulin-sensitizing and antidiabetic effects of G-Rb1 results from a reduction in ectopic fat accumulation, mediated by inhibition of lipolysis in adipocytes. Methods: Obese and diabetic db/db mice were treated with daily doses of 20 mg/kg G-Rb1 for 14 days. Hepatic fat accumulation was evaluated by measuring liver weight and triglyceride content. Levels of blood glucose and serum insulin were used to evaluate insulin sensitivity in db/db mice. Lipolysis in adipocytes was evaluated by measuring plasma-free fatty acids and glycerol release from 3T3-L1 adipocytes treated with G-Rb1. The expression of relevant genes was analyzed by western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay kit. Results: G-Rb1 increased insulin sensitivity and alleviated hepatic fat accumulation in obese diabetic db/db mice, and these effects were accompanied by reduced liver weight and hepatic triglyceride content. Furthermore, G-Rb1 lowered the levels of free fatty acids in obese mice, which may contribute to a decline in hepatic lipid accumulation. Corresponding to these results, G-Rb1 significantly suppressed lipolysis in 3T3-L1 adipocytes and upregulated the perilipin expression in both 3T3-L1 adipocytes and mouse epididymal fat pads. Moreover, G-Rb1 increased the level of adiponectin and reduced that of tumor necrosis factor-${\alpha}$ in obese mice, and these effects were confirmed in 3T3-L1 adipocytes. Conclusion: G-Rb1 may improve insulin sensitivity in obese and diabetic db/db mice by reducing hepatic fat accumulation and suppressing adipocyte lipolysis; these effects may be mediated via the upregulation of perilipin expression in adipocytes.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.230-237
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods: A genetically engineered $Apc^{Min/+}$ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results: After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-$1{\alpha}$ (IL-$1{\alpha}$), IL-$1{\beta}$, IL-6, tumor necrosis factor-${\alpha}$, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.

• Journal of Life Science
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• v.28 no.9
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• pp.1016-1021
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• 2018

Clostridium difficile toxin A causes pseudomembranous colitis. The pathogenesis of toxin A-induced colonic inflammation includes toxin A-dependent epithelial cell apoptosis, resulting in the loss of barrier function provided by epithelial cells against luminal pathogens. Toxin A-dependent epithelial cell apoptosis has been linked to toxin A-induced production of reaction oxygen species and subsequent p38MAPK activation; $p21^{CIP1/WAF1}$ upregulation-dependent cell cycle arrest; cytoskeletal disaggregation; and/or the induction of Fas ligand on epithelial cells. However, the molecular mechanisms underlying toxin A-induced apoptosis remain poorly understood. This study tested whether toxin A could block the Wnt signaling pathway, which is involved in gut epithelial cell proliferation, differentiation and antiapoptotic progression. Toxin A treatment of nontransformed human colonocytes (NCM460) rapidly reduced ${\beta}$-catenin protein, an essential component of the Wnt signaling pathway. Exposure of mouse ileum to toxin A also significantly reduced ${\beta}$-catenin protein levels. MG132 inhibition of proteasome-dependent protein degradation resulted in the recovery of toxin A-mediated reduction of ${\beta}$-catenin, indicating that toxin A may activate intracellular processes, such as $GSK3{\beta}$, to promote degradation of ${\beta}$-catenin. Immunoblot analysis showed that toxin A increased active phosphorylation of $GSK3{\beta}$. Because the Wnt signaling pathway is essential for gut epithelial cell proliferation and anti-apoptotic processes, our results suggest that toxin A-mediated inhibition of the Wnt signaling pathway may be required for maximal toxin A-induced apoptosis of gut epithelial cells.

• Applied Biological Chemistry
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• v.15 no.1
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• pp.19-25
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• 1972

A kind of peptide which posseses an yeaststatic activity was isolated from Astragalus membranaceus Bunge and following characteristics was obtained. 1. The isoelectric pH of this peptide was 8.2 and histidine, an alkaline amino acid, was identified from this peptide. 2. This substance showes conspicuous heat stability and does not indicate any remarkable reduction of yeaststatic activity even for 5 hours treatment at $100^{\circ}C$. or for 30 minutes at $121^{\circ}C$. 3. The inhibitory activity of the yeast growth is not originated from the yeastcidal action but yeaststatic effect of this sample. 4. The sample shows strong stability ranging from pH 2 to 10. 5. The saccharide; glucose, sucrose, maltose, gives no effect on the yeaststatic activity of the sample even high concentration, 15 percent, and also no effect gives by magnesium, calcium and phosphate salts. 6. The available concentration of this sample on the inhibition of yeast growth was located at the ppm extent, for example, the concentration of fifty percent growth inhibition to Saccharomyces cerevisiae or S. carsbergensis was 4 ppm and 3 ppm to Candida pulcherrima, 13 ppm to S. coreanus, 18 ppm to S. sake and 38 ppm to C. tropicalis. 7. On the alcohol fermentation of S. coreanus, the peptide, an yeast growth inhibitor, gives no effect at all. 8. This substance is named as Astradix-P (Astragalus membranaceus, Radix, Peptide).

• 한국생물공학회:학술대회논문집
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• 2003.04a
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• pp.40-44
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• 2003

Soil-borne infectious disease including Pythium aphanidermatum and Rhizoctonia solani causes severe damage to plants, such as cucumber. This soil-borne infectious disease was not controlled effectively by chemical pesticide. Since these diseases spread through the soil, chemical agents are usually ineffective. Instead, biological control, including antagonistic microbe can be used as a preferred control method. An efficient method was developed to select an antagonistic strain to be used as a biological control agent strain. In this new method, surface tension reduction potential of an isolate was included in the ‘decision factor’ in addition to the other factors, such as growth rate, and pathogen inhibition rate. Considering these 3 decision factors by a statistical method, an isolate from soil was selected and was identified as Bacillus sp. GB16. In the pot test, this strain showed the best performance among the isolated strains. The lowest disease incidence rate and fastest seed growth was observed when Bacillus sp. GB16 was used. Therefore this strain was considered as plant growth promoting rhizobacteria (PGPR). The action of surface tension reducing component was deduced as the enhancement of wetting, spreading, and residing of antagonistic strain in the rhizosphere. This result showed that new selection method was significantly effective in selecting the best antagonistic strain for biological control of soil-borne infectious plant pathogen. The antifungal substances against P. aphanidermatum and R. solani were partially purified from the culture filtrates of Bacillus sp. GB16. In this study, lipopeptide possessing antifungal activity was isolated from Bacillus sp. GB16 cultures by various purification procedures and was identified as a surfactin-like lipopeptide based on the Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), high performance liquid chromatography mass spectroscopy (HPLC-MS), and quadrupole time-of-flight (Q-TOF) ESI-MS/MS data. The lipopeptide, named GB16-BS, completely inhibited the growth of Pythium aphanidermatum, Rhizoctonia solani, Penicillium sp., and Botrytis cineria at concentrations of 10 and 50 mg/L, respectively. A novel method to prevent the foaming and to provide oxygen was developed. During the production of surface active agent, such as lipopeptide (surfactin), large amount of foam was produced by aeration. This resulted in the carryover of cells to the outside of the fermentor, which leads to the significant loss of cells. Instead of using cell-toxic antifoaming agents, low amount of hydrogen peroxide was added. Catalase produced by cells converted hydrogen peroxide into oxygen and water. Also addition of corn oil as an oxygen vector as well as antifoaming agent was attempted. In addition, Ca-stearate, a metal soap, was added to enhance the antifoam activity of com oil. These methods could prevent the foaming significantly and maintained high dissolved oxygen in spite of lower aeration and agitation. Using these methods, high cell density, could be achieved with increased lipopeptide productivity. In conclusion to produce an effective biological control agent for soil-borne infectious disease, following strategies were attempted i) effective screening of antagonist by including surface tension as an important decision factor ii) identification of antifungal compound produced from the isolated strain iii) novel oxygenation by $H_2O_2-catalase$ with vegetable oil for antifungal lipopeptide production.

• BMB Reports
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• v.32 no.4
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• pp.339-344
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• 1999

We studied the effects of ginsenosides in immature rats based upon the previous results that ginseng has a suppressive or anticonvulsive activity. To examine the suppressive effect of ginsenosides on kainic acid-induced seizures, the severities and frequencies were observed for 4 h after injection of kainic acid (KA; i.p., 2 mg/kg b.w.) using 10-day-old male Sprague-Dawley rats ($22{\pm}2\;g$). Protopanaxadiol saponins such as ginsenoside-Rb1 (Rb1), ginsenoside-Rb2 (Rb2), ginsenoside-Rc (Rc), and ginsenoside-Rd(Rd) generally reduced the seizure activities while protopanaxatriol saponins such as ginsenoside-Rg1 (Rg1) and ginsenoside-Re (Re) rather increased stereotypic "paddling-like" movements. When vinyl-GABA (v-G) was injected together with Rb1 or Rc, KA-induced seizure severities were additionally reduced only by the injection of Rc, but not by Rb1. The level of gamma isozyme of protein kinase C (PKC-${\gamma}$) in the hippocampus increased about three times as much as that of normal rats at 4 h after KA injection. The increased level of PCK-${\gamma}$ by KA was significantly reduced to about 35% by the coinjection with v-G alone, but it was not changed by v-G together with Rb1 or Rc. The increased level of PKC-${\gamma}$ at 4 h after injection of KA was not consistent with the reduction of seizure severities between Rb1 and Rc. These results suggest that Rc and Rb1 may reduce seizure severity independent of PKC-${\gamma}$ levels, and Rc may additionally act with v-G regarding the GABA metabolism during the stage of KA-induced seizures in the immature rats.

• Korean Journal of Acupuncture
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• v.24 no.2
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• pp.217-230
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• 2007

Objectives : Ulcerative colitis or Crohn's disease has been recognized as Ha-ri (下痢) or Jang-Byok in Korean oriental medicine. A purpose of the present study is to investigate the anti-inflammatory effect of moxi-tar herbal acupuncture at LI4 (HapGok) on 2,4,6-trinitrobenzene sulphonic acid (TNBS) induced colitis in rats and further elucidate the possibility of herbal acupuncture on ulcerative colitis which is chronic inflammatory disease of the gastrointestinal tract. Methods : Sprague-Dawley rats, weighing $170{\sim}190$ g, were subjected to intrarectal injection of either saline (300 ${\mu}l$, 500 ${\mu}l$) for a control or 2,4,6-trinitrobenzene sulphonic acid (TNBS) (300 ${\mu}l$, 500 ${\mu}l$) for a colitis, Moxi-tar (20 mg/ml) were subcutaneously injected to the LI4 just after the secondary injection time of TNBS in rats. To study the effects of Moxi-tar acupuncture in LI4, body weight, RBC count, WBC count, total protein, Paw edema rate, rate of protein leakage into CMC-pouch fluid, IgG levels and IgM levels were observed. Results: Moxi-tar acupuncture in LI4 on TNBS-induced colitis inhibited the body weight lose rate but not effect RBC, WBC count. In addition, it inhibited the reduction of total protein concentration, paw edema, rate of protein leakage into CMC-pouch fluid, IgG levels and IgM levels. Conclusions : It is suggested that moxi-tar herbal acupuncture at LI4 helps to recover TNBS-induced colitis and plays an important role for an treatment of the irritable bowel syndrome (IBS).

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.11
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• pp.1634-1639
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• 2010

The purpose of this study is to determine the possibility of using Kalopanax pictus leaf as natural health food source. The contents of proximate and antioxidative nutrients of Kalopanax pictus leaf were measured. The contents of carbohydrate, crude protein, crude lipid and ash were 41.42%, 45.23%, 3.29% and 10.07%, respectively. The calories of Kalopanax pictus leaf was 401.52 kcal/100 g and total dietary fiber was 30.37%. The percentages of water soluble dietary fiber to insoluble dietary fiber were 9.16% and 21.21%, respectively. The protein contained a total of 18 different kinds of amino acids. The contents of essential and non-essential amino acids were 10.51 g/100 g and 17.69 g/100 g. The K was the largest mineral followed by P, Ca, and Mg, which means Kalopanax pictus leaf is alkali material. The contents of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids were 1.56 g/100 g, 0.11 g/100 g and 1.84 g/100 g, respectively. The antioxidant activity of 70% ethanol extract and fractions of the Kalopanax pictus leaf has been determined by the scavenging of the stable radical DPPH; the result showed that the ethyl acetate fraction was the most active, as the amount required for 50% reduction of DPPH after 30 mins ($RC_{50}$) was $105.7\;{\mu}g$, followed by 70% ethanol extract ($247.3\;{\mu}g$), hexane fraction ($120.7\;{\mu}g$), chloroform ($107.3\;{\mu}g$), butanol fraction ($110.1\;{\mu}g$) and aqueous fraction ($491.9\;{\mu}g$).

• Journal of Chest Surgery
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• v.29 no.8
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• pp.807-815
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• 1996

The protective effect of'ischemic preconditioning'on ischemid-reperfusion injury of heart has been reported in various animal species. but without known mechAnism in detail, In An attempt to investigate the cardioprotective mechanism of ischemic preconditioning, we examined the effects of nitric oxide(UO) synthesis in preconditioned heart of rat The isolated hearts perfused by Langendorfr's method were ex- posed to 30min global ischemia followed by 30min reperfusion with oxygenated Krebs-Henseleit(K-H) sol- ution. Ischemic preconditioning was performed with three episodes of Sm n ischemia and Smin repeyfusion before the induction of prolong ischemia(30min)-reperfusion(30min). Ischemic preconditioning prevented the depression of cardiac function(left ventricular pressure .K heart rate) observed in the ischemia- reperfusion hearts and reduced the release of lactate dehydrogenase during the reperfusion period. On electromicroscopic pictures, myocardial ultrastructures wore relatively well preserved in isthemic preconditioned hearts. N6_nitro-L-arginine methyl ester(L-NAME) an inhibitor of L-arginine citric oxide pathway, was infused at a rate O.Smllmin In a dose of 10mg kg-1 before the initial ischemic preconditioning. neither the protection of cardiac function nor the reduction of LDH releAse in ischemic preconditioning hearts was altered in the presence of added L-NAME On ultrastructural finding, the preservation of morphology in ischemic preconditioning heart was not change by the pretreatment of L-UAME. The failure of the WO synthesis inhibitor to reduce t e effect of ischemic preconditioning may be related to be species specific in that NO may allot be the trigger for ischemic preconditioning in rats.

• Parasites, Hosts and Diseases
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• v.44 no.4 s.140
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• pp.361-366
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• 2006

Sustained-releasing praziquantel (SRP) tablet was designed for single dose treatment regimen of clonorchiasis. A previous pre-clinical study confirmed its sustained-releasing characteristics and a better cure rate than conventional praziquantel (PZQ). In this clinical study, the pharmacokinetics of this SRP tablet were investigated in human volunteers (phase 1; 12 volunteers), and its curative efficacy was examined in clonorchiasis patients (phase 2; 20 volunteers). In the phase 1 clinical study, blood concentrations of both tablets showed wide individual variation. The $AUC_{last}$ of SRP was $497.9{\pm}519.0ng{\cdot}hr/ml\;(mean{\pm}SD)$ and PZQ of $628.6{\pm}695.5\;ng{\cdot}hr/ml$, and the $AUC_{inf}$ of SRP was $776.0{\pm}538.5\;ng{\cdot}hr/ml$ and of PZQ $658.6{\pm}709.9\;ng{\cdot}hr/ml$. $C_{max}$ values of SRP and PZQ were $90.7{\pm}82.2ng/ml\;and\;214.9{\pm}251.9\;ng/ml$, and $T_{max}$ values were $3.42{\pm}1.43\;hr\;and\;1.96{\pm}1.23\;hr$, respectively. SRP tablets showed similar AUC values, but lower $C_{max}$ and longer $T_{max}$ values than PZQ. In the phase 2 study, SRP at 30 mg/kg (single dose) achieved a 60% cure rate and a 95.5% egg reduction rate. The cure rate of a single dose SRP was unsatisfactory compared with that of the conventional PZQ dose, but much better than that achieved by a single dose PZQ.