• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.1
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• pp.124-133
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• 2010

The object of this study was to obtain acute information single oral dose toxicity of Mahwangbujaseshin-tang extracts, with mouse bone marrow cell micronucleus test for detecting possible genotoxicity. In order to observe the 50% lethal dose, approximate lethal dosage, maximum tolerance dosage and target organs, test articles were once orally administered to ICR mice at dose levels of 2000, 1000, 50 mg/kg according to the recommendation of KFDA Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines with organ weights of 12 types of principle organs. In addition, after twice oral treatment of Mahwangbujaseshin-tang extracts 2000, 1000 and 500 mg/kg, we checked the changes on the number of MNPCE. We could not find any mortality, clinical signs, changes in the body weight and gross findings upto 2000 mg/kg treated group. The limited dosages in rodents except for increases of lymphoid organ weights and hypertrophy encounted as results from pharmacological effects of Mahwangbujaseshin-tang extracts, immune modulator effects with some sporadic accidental findings not toxicological signs. No evidence of increases of MNPCE numbers were also detected in all three different dosages of Mahwangbujaseshin-tang extracts treated mice. The results obtained in this study suggest that the LD50 and ALD of Mahwangbujaseshin-tang extracts in mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. And the results of mouse bone marrow micronucleus test of Mahwangbujaseshin-tang extracts is negative results.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.185-192
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• 2006

To elucidate the molecular mechanisms associated with early renal injury induced by gentamicin, the most commonly used antibiotics worldwide in the treatment of Gram-negative bacterial infections. We have identified genes differentially expressed at different duration of gentamicin administration. C57BL/6 female mice were treated daily with gentamicin (20 mg/kg, 100 mg/kg, and 200mg/kg) for 7 days and then sacrificed at day 1, 3, and 7 after administration. Standard blood biochemistry and histopathological observation indicative of nephrotoxicity were made. Total RNA was extracted from the kidney for microarray analysis using Affymetrix $GeneChip^{\circledR}$. Five hundred and seventy eight genes were identified as being either up-or down-regulated over 2-fold changes during early renal injury (p<0.05) and were analyzed by hierarchical clustering. The results showed that the genes involved in early immune responses were differentially regulated during early renal injury. Principal component analysis (PCA) confirmed sample separation according to the degree of renal toxicity. In addition, we identified two potential biomarkers that may predict early renal toxicity. This data may contribute to elucidate of the genetic events during early renal injury and to discover the potential biomarkers for nephrotoxicity induced by gentamicin.

• Herbal Formula Science
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• v.19 no.1
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• pp.145-160
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• 2011

Objectives : Rehmannia glutinosa has been used extensively in Korean traditional medicine. Although thorough clinical trials are lacking, Various pharmacological actions for Rehmannia glutinosa has been identified newly using animal models. In addition, it was reported that reactive intermediates, potentially causing toxic effects, was isolated from one of components in Rehmannia glutinosa. In this article, it is purposed for explanation and introduction of new studies for Rehmannia glutinosa in terms of pharmacological action and toxicology. Methods : New studies for Rehmannia glutinosa were reviewed and summarized in terms of pharmacological action and toxicity. Results and Conclusions : Rhmannia glutinosa and its components including iridoids, saccharides, as well as amino acid, showed a variety of pharmacological actions on the blood system, immune system, endocrine system, cardiovascular system and the nervous system. In addition, it was identified that aucubin, one of major components of Rhmannia glutinosa was biotransformed to reactive intermediates by ${\beta}$-glycosidase and acid-hydrolysis, resulting in forming aucubigenin- albumin adduct. Even if a lot of new pharmacological actions has been identified, it should be considered for Rhmannia glutinosa to contain the material producing reactive intermediates which may induce the side effects.

• The Journal of Internal Korean Medicine
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• v.32 no.3
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• pp.323-333
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• 2011

Objectives : Zingberis Rhizoma (ZR) and Glycyrrihizae Radix (GR) have been widely used to prevent or treat allergic diseases. However, relatively little research has been conducted on the immune response to Senggang Gamcho-tang (SG) in a mixture of ZR and GR. The purpose of this study was to determine antiallergic effects of Senggang Gamcho-tang (SG) extracts ZR and GR on activity of murine splenocytes. Methods : This study was performed to investigate the effect of SG in mice, using in vitro experiments. Cells were treated with SG extract (1 ${\mu}g$/ml, 10 ${\mu}g$/ml and 100 ${\mu}g$/ml) plus Con A (2 ${\mu}g$/ml) and ZR (6.6 ${\mu}g$/ml and 66 ${\mu}g$/ml), GR (3.3 ${\mu}g$/ml and 33 ${\mu}g$/ml) respectively for 48 hrs. The production of IFN-${\gamma}$ and IL-4 were determined by ELISA. Results : No toxicity was found in splenocytes treated with SG extract for 48 hrs at the concentration of 0 ${\mu}g$/ml, 1 ${\mu}g$/ml, 10 ${\mu}g$/ml and 100 ${\mu}g$/ml, respectively. The production of IFN-${\gamma}$ increased to 23,968.7 pg/ml (p<0.001) while that of IL-4 significantly decreased to 14.1 pg/m l(p<0.05) only at the SG concentration of 100 ${\mu}g$/ml. With the GR concentration of 33 ${\mu}g$/ml in SG extract, the production of IFN-${\gamma}$ rose to 32,102.2 pg/ml (p<0.001) while that of IL-4 (p<0.05) declined to 34.2 pg/ml. However, there was no significant observation with regard to the effect of ZR on production of IFN-${\gamma}$ and IL-4. Conclusions : This study suggests an antiallergic effect of Senggang Gamcho-tang, which leads to the implication that SG extract may be used to enhance human immune function.

• Korean Journal of Oriental Medicine
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• v.15 no.3
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• pp.83-91
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• 2009

$\beta$-glucan is a fiber-type complex sugar (polysaccharide) derived from the cell wall of baker's yeast, oat and barley fiber, and many medicinal mushrooms, such as maitake. The primary uses of $\beta$-glucan are to enhance the immune system, to lower blood cholesterol levels and to treat tumor. $\beta$-glucan has no systemic toxicity in mice, therefore it needed clinical trail to prove efficacy and safety for human. The subjects total 56 healty volunteers were divided into two groups including taken $\beta$-glucan tablet group and placebo group. Subjects were taken two tablets per oral for 4 weeks. They had agreed to take part in this experiment, and didn't take any other clinical trail products. After 4 weeks blood of subjects were checked. The check list are TNF-$\alpha$, INF-$\gamma$, IL-2, IL-4, total WBC, differential WBC, RBC, hemoglobin, platelet, MCV, MCH, MCHC, HCT, Na, K, Ca, Cl, AST, ALT, ALP, $\gamma$-GTP, total protein, triglyceride, total cholesterol, total bilirubin, albumin, uric acid, creatinine, BUN, pH, protein, glucose, ketone body, blood, bilirubin. We evaluated efficacy by cytokines that compare before and after taking. Collected data were analyzed as two sample t-test, chi-square test and ANOVA using SAS V.9.1.This study results are that in TNF-$\alpha$ of $1^{st}$ efficacy measurement item, all of two groups figure were increased significantly compare to before figure. In IL4 of $2^{nd}$ efficacy measurement item, experimental group figure were decreased significantly but placebo group figure were increased. The conclusions show that based on the above results, $\beta$-glucan has favorable effect to enhance immune system, especially IL4 results showed that it has effect to improve the allergic immune system.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.627-637
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• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1499-1506
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• 2016

Background: Crocus sativus and its major constituent crocin are well established to have anti-cancer properties in breast cancer cells (MCF-7). However the role of C. sativus extract (CSE) and crocin on caspase signaling mediated MCF-7 cell death at molecular level is remains unclear. In this study, we tried to unravel role of CSE and crocin on caspase mediated MCF-7 cells death and their in vivo preclinical toxicity profiling and immune stimulatory effect. Materials and Methods: CSE extract was fractionated by HPLC and crocin was isolated and characterized by NMR, IR, and MS. MCF-7 cells were treated with both CSE and crocin and expression of Bcl-2 and Bax was assessed after 24 and 36 hours. Furthermore, caspase 3, caspase 8 and caspase 9 expression was determined by Western blotting after 24 hours of treatment. DNA fragmentation analysis was performed for genotoxicity of CSE and crocin in MCF-7 cells. The in vivo toxicity profile of CSE (300 mg/kg of b.wt) was investigated in normal Swiss albino mice. In addition, peritoneal macrophages were collected from crocin (1, 1.5 and 2 mg/kg body weight) treated mice and analyzed for ex vivo yeast phagocytosis. Results: Immunoblot analysis revealed that there was time dependent decline in anti-apoptotic Bcl-2 with simultaneous upregulation of Bax in CSE and crocin treated MCF-7 cells. Further CSE and crocin treatment downregulated caspase 8 and 9 and cleaved the caspase 3 after 24 hours. Both CSE and crocin elicited considerable DNA damage in MCF-7 cells at each concentration tested. In vivo toxicity profile by histological studies revealed no observable histopathologic differences in the liver, kidney, spleen, lungs and heart in CSE treated and untreated groups. Crocin treatment elicited significant dose and time dependent ex vivo yeast phagocytosis by peritoneal macrophages. Conclusions: Our study delineated involvement of pro-apoptotic and caspase mediated MCF-7 cell death by CSE and crocin at the molecular level accompanied with extensive DNA damage. Further we found that normal swiss albino mice can tolerate the maximum dose of CSE. Crocin enhanced ex vivo macrophage yeast phagocytic ability.

• Clean Technology
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• v.17 no.3
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• pp.273-279
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• 2011

The physicochemical properties of manufactured nanomaterials can vary depending upon the methods of manufacture, although the utilized raw materials are same. Hence, the toxicity can also vary based on the methods of nanomaterials manufacture. In this study, we compared the toxicity effect of two types of CNTs (MWCNT, multi-walled carbon nanotube; SWCNT, single-walled carbon nanotube) that differ in length and wall number. In case of MWCNTs, inflammatory responses were more strongly induced in longer groups, whereas body weights more clearly decreased in shorter groups. SWCNT significantly decreased the relative weights of brain and kidney, and the inflow of immune cells and the hematological changes were observed significantly on day 1 and day 7 after exposure, respectively. Our results showed that the length and wall number of CNTs can serve as critical factors in the exhibited inflammation and toxicity.

• Advances in Traditional Medicine
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• v.9 no.1
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• pp.74-82
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• 2009

Pharmacological investigations were carried out with aqueous methanolic extract (AME) of Swietenia mahagoni (L.) Jacq. (Meliaceae) leaves. Acute toxicity studies revealed that the $LD_{50}$ dose of AME was 600 mg/kg, i.p. AME was found to possess significant anti-inflammatory activity in acute, sub-chronic and chronic models of inflammation. AME selectively inhibited cyclooxygenase (COX)-2 activity, which is involved in arachidonic acid metabolism and biosynthesis of prostaglandins under inflammatory conditions. Treatment with AME significantly enhanced total peritoneal cell count and the number of macrophages in normal mice, which revealed that AME may also alter the immune response along with its anti-inflammatory effect. The saponins or the alkaloids present in AME may be responsible for the anti-inflammatory activity.

• Korean Journal of Plant Resources
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• v.2 no.1
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• pp.1-214
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• 1989

There shoul be high possibility of preventive and immune eficacy aqainst cancer when the anti-cancer plants are properly utilized in human dietary life as it is evident that considerable part of wild plantd or both medicinal use and ood are growing naturally in the mountainous area in korea, some of which have ben proved to be anti-cancer plants. this study, at this initial stage, has been done to acquire the fundamentals of 235 kinds of ante-cancer plants growing naturally in korea. from the results o thisresearch, the anti-cancer plants have been sorted out by amily and its number. and also the status of regional distribution of those plants and the kinds of anti-cancer plants used for both medicine and food were studied and experimented to see the medical efficacy against anti-tumor. this experiments were conduced in accodance with the total packed cell volume method and cyto toxicity method.