• Archives of Pharmacal Research
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• v.24 no.4
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• pp.323-326
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• 2001

Previous studies have demonstrated that CW252053, a quinazoline antifolate, exhibits potent inhibitory activity against thymidylate synthase (TS) as well as cytotoxic activity against tumor cell lines in vitro. In this studys, we evaluated the in vivo antitumor efficacy of CW252053 in the mouse tumor model. Female B6D2F$_1$ mice were injected with LY3.7. 2C TK-/- (thymidine kinase deficient mouse Iymphoma) cells into the gastrocnemius muscle. Then, CW252053 was administered twice daily by intraperitoneal injection for 10 days, and tumor growth was monitored daily by leg diameter measurement. All animals in the vehicle, 5-FU, and low dose (30mgmg/kg CW252053 treated groups died between days 12 and 23 because of the tumor burden. In contrast, dosing with 60 mg/kg of CW252053 produced a cure rat against tumor growth of 37.5% and a survival rate of 50%. Even more significantly, a higher dose of CW252053 (120 mg/kg) elicited both a 100% cure rate and a 100% survival rate at the termination of the study, confirming that this compound has very potent in vivo antitumor activity against tumor growth. During the experimental period of this study no signs of toxicity were observed even at the high CW252053 dosage rate of 120 mg/kg.

• Archives of Pharmacal Research
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• v.17 no.3
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• pp.145-149
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• 1994

Intravenous administration of hydro-methanolic extract of Cyperus scariosus (3-10 mg/kg) produced hypotensive and bradcardiac effects. These effects remianed unaltered in atropinized animals indicating that cardiovascular effects of the plant extract are not medliated through activation of muscarinic receptors. In the in vitro studies, it suppressed the spontaneous contractions of guinea-pig paired atria, rat ulterus and rabbit jejunum in a concentration-dependent (0.1-1 mg/ml) manner. It also inhibited histanmine or acetylcholine-induced contractions of guinea-pig ieum indicating non-sepcific spasmolytic action. In rabbit aorta, it inhibited norepinephrine $(10\;mu{M)}$ as well as $K^+$ (80mM)-induced contractions at similar concentrations (0.1-1 mg/ml). These data indicate that cyperus scariosus contains $Ca^{2+}$ channel blocker-like constituent(s) which may explain hypotensive effect observed in vivo and the general spasmolytic activity of plant explain its folkloric use in diarrhoea.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.7
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• pp.1049-1056
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• 2007

This study was conducted to compare the methane ($CH_4$) production estimated by in vivo (sulfur hexafluoride tracer technique ($SF_6$)) with that of two in vitro rumen simulation (RUSITEC) and gas production (IVGPT)) techniques. Four adult dry Holstein cows, aged $7.4{\pm}3.0$ years and weighing $697{\pm}70$ kg, were used for measuring methane production from five diets by the $SF_6$ technique. The experimental diets were alfalfa hay ($D_1$), corn silage + soybean meal (SBM) (910: 90, $D_2$), Italian rye grass hay +SBM (920: 80, $D_3$), rice straw +SBM (910: 90, $D_4$) and Sudan grass hay +SBM (920: 80, $D_5$). Each diet was individually fed to all 4 cows and 5 feeding studies of 17 d each were conducted to measure the methane production. In the RUSITEC, methane production was measured from triplicate vessels for each diet .In vitro gas production was measured for each of the diets in triplicate syringes. The gas produced after 24 and 48 h was recorded and gas samples were collected in vacuum vials and the methane production was calculated after correction for standard temperature and pressure (STP). Compared to the $SF_6$ technique, estimates of methane production using the RUSITEC were lower for all diets. Methane production estimated from 24 h in vitro gas production was higher (p<0.001) on $D_1$ as compared to that measured by $SF_6$, whereas on $D_2$ to $D_5$ it was lower. Compared to $SF_6$, methane production estimated from 48 h in vitro gas production was higher on all diets. However, methane estimated from the mean of the two measurement intervals (24+48 h/2) in IVGPT was very close to that of $SF_6$ (correlation 0.98), except on $D_1$. The results of our study confirmed that IVGPT is reflective of in vivo conditions, so that it could be used to generate a database on methane production potential of various ruminant diets and to examine strategies to modify methane emissions by ruminants.

• Korean Journal of Pharmacognosy
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• v.31 no.2
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• pp.190-195
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• 2000

In the previous reports, we selected 80% MeOH extract of 7 herbs including Scutellariae Radix(SR), Paeoniae Radix Rubra(PRR), Moutan Cortex(MC), Angelicae Gigantis Radix(AGR), Crataegi Fructus(CF), Bambusae Caulis in Taeniam(BCT) and Cinnamomi Ramulus(CR), which exhibited the inhibitory effect on HMG-CoA reductase and DPPH free radical scavenging effect in vitro, and antihyperlipidemic effects on antihyperlipidemic rats induced by Triton WR 1339 in vivo. Among them, SR, MC, AGR and BCT showed significant suppression of elevated serum LDL-cholesterol level, and AGR and CF showed significant liver weight increase on high cholesterol diet induced hyperlipidemic mice. And, SR, PRR, AGR, BCT and CR significantly suppressed the elevated serum total cholesterol and triglyceride levels on corn oil induced hyperlipidemic rats. Then, in order to research new antihyperlipidemic agents from the oriental medicinal herbs, we chose SR, AGR, CR and BCT which have the antihyperlipidemic effect in vitro and in vivo, and those herbs were systematically fractionated with organic solvent. EtOAc fraction of SR, hexane fraction of BCT, AGR and chloroform fraction of CR exhibited remarkably inhibitory effect on HMG-CoA reductase activity.

• Preventive Nutrition and Food Science
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• v.19 no.1
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• pp.10-18
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• 2014

In this study, Woongjin fermented red ginseng extract (WFRG) was evaluated for its potential ability to act as an adjuvant for the immune response of mice. For the in vitro study, macrophages were treated with serial concentrations ($1{\mu}g/mL$, $10{\mu}g/mL$, and $100{\mu}g/mL$) of WFRG. For in vivo studies, mice were administered different concentrations (10 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day) of WFRG orally for 21 days. In vitro, the production of nitric oxide and TNF-${\alpha}$ by RAW 264.7 cells increased in a dose-dependent manner. In vivo, WFRG enhanced the proliferation of splenocytes induced by two mitogens (i.e., concanavalin A and lipopolysaccharide [LPS]) and increased LPS-induced production of TNF-${\alpha}$ and IL-6, but not IL-$1{\beta}$. In conclusion, WFRG has the potential to modulate immune function and should be further investigated as an immunostimulatory agent.

• The Korean Journal of Zoology
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• v.26 no.2
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• pp.69-81
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• 1983

The biological effect of hyperthermia on the SCK tumor cells in vitro were analyzed in several respects. A comparision of the survival curve of SCK tumor cells in vitro and in vivo following hyperthermia demonstrated that the cytocidal effect of heating is far greater on the cells in vivo than on the cells in vitro. The pH change in the SCK tumor upon being heated at $43.5^\\circC$ started out at 7.05 and increased to 7.18 during the first 7 min of heating and then rapidly declined to 6.67 by 30 min. Contrary to the decrease in pH in the heated tumors, the pH in the muscle increased significantly when heated to $43.5-45.0^\\circC$. Following hyperthermia at $43.5^\\circC$ for 30 min, a maximum increase in the lactic acid content in the tumor and liver was observed at 1 hr and 3 hr, respectively. The increase in the tumor was followed by a gradual decrease below the control level, whereas the increase in the liver was maintained at quite a steady level for 24 hr. The hyperthermia at $43.5^\\circC$ for 1 hr exhibited a general tendency that high molecular proteins decrease markedly, whereas most of low molecular proteins increase. The most prominent change was that the heat shock protein 70K increased significantly along with other low molecular proteins in heat shocked cells.

• Molecules and Cells
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• v.43 no.6
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• pp.517-529
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• 2020

Carboxyl-terminal binding proteins (CtBPs) are transcription regulators that control gene expression in multiple cellular processes. Our recent findings indicated that overexpression of CtBP2 caused the repression of multiple bone development and differentiation genes, resulting in atrophic nonunion. Therefore, disrupting the CtBP2-associated transcriptional complex with small molecules may be an effective strategy to prevent nonunion. In the present study, we developed an in vitro screening system in yeast cells to identify small molecules capable of disrupting the CtBP2-p300 interaction. Herein, we focus our studies on revealing the in vitro and in vivo effects of a small molecule NSM00158, which showed the strongest inhibition of the CtBP2-p300 interaction in vitro. Our results indicated that NSM00158 could specifically disrupt CtBP2 function and cause the disassociation of the CtBP2-p300-Runx2 complex. The impairment of this complex led to failed binding of Runx2 to its downstream targets, causing their upregulation. Using a mouse fracture model, we evaluated the in vivo effect of NSM00158 on preventing nonunion. Consistent with the in vitro results, the NSM00158 treatment resulted in the upregulation of Runx2 downstream targets. Importantly, we found that the administration of NSM00158 could prevent the occurrence of nonunion. Our results suggest that NSM00158 represents a new potential compound to prevent the occurrence of nonunion by disrupting CtBP2 function and impairing the assembly of the CtBP2-p300-Runx2 transcriptional complex.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3735-3742
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• 2013

Background: Cardamom (Elettaria cardamom), also known as "Queen of Spices", has been traditionally used as a culinary ingredient due to its pleasant aroma and taste. In addition to this role, studies on cardamom have demonstrated cancer chemopreventive potential in in vitro and in vivo systems. Nevertheless, the precise poly-pharmacological nature of naturally occurring chemo-preventive compounds in cardamom has still not been fully demystified. Methods:In this study, an effort has been made to identify the proapoptopic, anti-inflammatory, anti-proliferative, anti-invasive and anti-angiogenic targets of Cardamom's bioactive principles (eucalyptol, alpha-pinene, beta-pinene, d-limonene and geraniol) by employing a dual reverse virtual screening protocol. Experimentally proven target information of the bioactive principles was annotated from bioassay databases and compared with the virtually screened set of targets to evaluate the reliability of the computational identification. To study the molecular interaction pattern of the anti-tumor action, molecular docking simulation was performed with Auto Dock Pyrx. Interaction studies of binding pose of eucalyptol with Caspase 3 were conducted to obtain an insight into the interacting amino acids and their inter-molecular bondings. Results:A prioritized list of target proteins associated with multiple forms of cancer and ranked by their Fit Score (Pharm Mapper) and descending 3D score (Reverse Screen 3D) were obtained from the two independent inverse screening platforms. Molecular docking studies exploring the bioactive principle targeted action revealed that H- bonds and electrostatic interactions forms the chief contributing factor in inter-molecular interactions associated with anti-tumor activity. Eucalyptol binds to the Caspase 3 with a specific framework that is well-suited for nucleophilic attacks by polar residues inside the Caspase 3 catalytic site. Conclusion:This study revealed vital information about the poly-pharmacological anti-tumor mode-of-action of essential oils in cardamom. In addition, a probabilistic set of anti-tumor targets for cardamom was generated, which can be further confirmed by in vivo and in vitro experiments.

• The Korea Journal of Herbology
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• v.28 no.4
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• pp.83-92
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• 2013

Objectives : Lespedeza Cuneata has been used to treat leukorrhea, asthma, stomach pain, diarrhea, acute mastitis, in Korean traditional medicine. According to recent studies, Lespedeza Cuneata has antioxidation, hypoglycemia, cell protective, insulin secretion, whitening, corpora cavernosa smooth muscle relaxation and antimicrobial activities, but it has been rarely conducted to evaluate the immuno-biological activity. The present study was examined to evaluate the anti-inflammatory effects of the Lespedeza Cuneata MeOH extract (LCE) in vivo and in vitro. Methods : In vitro, inflammatory mediators, such as cytokines, nitric oxide and prostaglandin $E_2$ were detected after the addition of LPS with or without LCE in Raw 264.7 macrophage cell line. In vivo, anti-edema effect of LCE was determined in the carrageenan-induced paw edema model in rats. Results : In vitro assay, LCE decreased release of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) via suppression of iNOS and COX-2 expression. LCE inhibited the phosphorylation of $I{\kappa}B$ indicating the suppression of NF-${\kappa}B$ pathway. In vivo assay, LCE significantly inhibited the formation of paw edema induced by carrageenan injection in rats. LCE effectively inhibited increases of hind paw skin thickness and inflammatory cell infilterations. Conclusion : These findings demonstrate that LCE has inhibitory effect on inflammatory mediators in LPS-activated Raw 264.7 cells and on paw edema in carrageenan-stimulated rats, showing the possibility of anti-inflammatory use of Lespedeza Cuneata.

• Journal of Acupuncture Research
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• v.23 no.4
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• pp.187-203
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• 2006

Objectives : This study was designed to investigate the antimetastatic and immunomodulating effects of Patriniae Radix. Methods : Acute and subacute cytotoxicity experiment of Patriniae Radix was performed. Antimetastatic experiment was administered in vitro and in vivo. To observe the immunomodulating effects of Patriniae Radix, FACS analysis and ELISA assay were performed. Results : There was no acute and subacute toxicity responses in mouse treated with Patriniae Radix. Antimetastatic experiment in vitro and in vivo showed that Patriniae Radix has antimetastatic effects. This research revealed that Patriniae Radix mediate cellular immunity response. As compared with control, the population of total T cell, helper T cell, cytotoxic T cell and macrophage were increased. The production of Th 1 type cytokines from splenocyte and cytokines which is associated with anti-tumor activity form macrophage were increased significantly. Conclusion Patriniae Radix Herbal-acupuncture appears to have considerable activity on the treatment of liver metastasis from colon26-L5 carcinoma cell line, and deserves further evaluation in this setting.