• Journal of Pharmacopuncture
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• v.19 no.4
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• pp.350-358
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• 2016

Objectives: This study was carried out to analyze the single dose toxicity of ShinEumHur (SEH) pharmacopuncture injected into the muscles of Sprague-Dawley rats. Methods: The SEH pharmacopuncture was made in a clean room at the Korean Pharmacopuncture Institute (K-GMP). After the mixing process with sterile distilled water had been completed, the pH was controlled to between 7.0 and 7.5. All experiments were conducted at Biotoxtech, an institution authorized to perform non-clinical studies under the Good Laboratory Practice (GLP) regulations. Sprague-Dawley rats were chosen for the pilot study. Doses of SEH pharmacopuncture, 0.25, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. We examined the survival rate, weights, clinical signs, mean hematology parameters, mean clinical chemistry, necropsy and histopathological findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion: The above findings suggest that treatment with SEH pharmacopuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

• The Korean Journal of Pesticide Science
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• v.15 no.2
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• pp.208-217
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• 2011

Pyrimisulfan is a herbicide. In order to register this new pesticide, the series of toxicity data on animal testing were reviewed to evaluate its hazards to consumers and also to determine its acceptable daily intake. Pyrimisulfan was excreted mostly by feces. It has low acute oral toxicity while it has no dermal, ocular irritation and skin sensitization (As the result of subchronic and chronic toxicity and carcinogenicity showed changes of hematology and liver.). Two-generation reproduction toxicity, genotoxicity, carcinogenicity and prenatal development toxicity were not proven. Therefore, the ADI for Pyrimisulfan is 0.1 mg/kg/ bw/day, based on the NOAEL of 10 mg/kg/ bw/day of 90-days repeated dose oral toxicity study in dogs while applying an uncertainty factor of 100.

• Journal of Dairy Science and Biotechnology
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• v.34 no.2
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• pp.91-98
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• 2016

The goal of this study was to develop hydrolyzed whey protein powder (23%-GNANA) manufactured with high content of sialic acid, a marker compound that is usually present at 7% concentration in GMP obtained from the milk protein. It is a safe food, used worldwide in infant and baby foods, etc. The test substance was prepared using (7% sialic acid containing) GMP as a raw material. Alcalase, an enzyme approved as a food additive, was used after separating sialic acid, with 100% efficiency, and 23%-GNANA (composed of 23% sialic acid and protein; product name: HELICOBACTROL-23), provided by MEDINUTROL Inc. (Korea), manufactured to have high (23%) content through ethanol soaking and enrichment. Bacterial reverse mutation (Ames) test was conducted in accordance with the GLP Guideline using the test substance specified above. To detect its mutagenicity potential in microorganisms, histidine auxotrophic strains of Salmonella typhimurium, TA98, TA100, TA1535, and TA1537, and tryptophan auxotrophic Escherichia coli strain, WP2uvrA, were used. The bacterial reverse mutation (Ames) test was performed using five concentrations of the test substances (0, 61.7, 185, 556, 1,670, $5,000{\mu}g/plate$). The evaluation did not reveal repetitive increase of colony generating values and positive criteria for reverse mutagenicity for any tested concentration in the five strains regardless of the presence of metabolic activation system, and no dose-dependency. In conclusion, the safety of 23%-GNANA test substance was verified by the bacterial reverse mutation test conducted before registration of 23%-GNANA as a food additive.

• Journal of Pharmacopuncture
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• v.13 no.4
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• pp.5-41
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• 2010

Objectives: This study was performed to analyse four week repeated dose toxicity of Sweet Bee Venom(Sweet BV) extracted from the bee venom in Beagle dogs. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLP) at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of four week repeated dose toxicity of Sweet BV which was administered at the level of 0.56mg/kg body weight which is eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14mg/kg as midium and low dosage, respectively. Equal amount of excipient(normal saline) to the Sweet BV experiment groups was administered as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups were appealed pain sense in the treating time compared to the control group, and hyperemia and movement disorder were observed around the area of administration in all experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. In the urine analysis, CBC and biochemistry didn't show any significant changes in the experiment groups compared with control group. 5. For weight measurement of organs, experiment groups didn't show any significant changes compared with control group. 6. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, cerebrum, liver, lung, kidney, and spinal cords were removed and conducted histologocal observation with H-E staining. In the histologocal observation of thigh muscle, cell infiltration, inflammatory, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes were depend on the dose of Sweet BV. But another organs were not detected in any abnormalities. 7. The proper high dosage of Sweet BV for the thirteen week repeated test in Beagle dogs may be 0.28mg/kg in one time. Conclusion: Above findings suggest that Sweet BV is relatively safe treatment medium. Further studies on the subject should be conducted to yield more concrete evidences.

• Toxicological Research
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• v.26 no.3
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• pp.209-216
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• 2010

Limb bud (LB) and central nerve system (CNS) cells were prepared from 12.5 day old pregnant female Crj:CD (SD) rats and treated with olaquindox and vitamin A. Cytotoxicity and inhibition on differentiation were measured in each cell. Three doses of olaquindox (4, 21 and 100 mgkg), and 0.2 and 75 mg/kg of vitamin A were administered to pregnant rat for 11 days from $6^{th}$ to $16^{th}$ of pregnancy. $IC_{50}$ values of olaquindox for proliferation and differentiation in CNS cell were 22.74 and $28.32\;{\mu}g/ml$ and 79.34 and $23.29\;{\mu}g/ml$ in LB cell and those values of vitamin A were 8.13 and $5.94\;{\mu}g/ml$ in CNS cell and 0.81 and $0.05\;{\mu}g/ml$ in LB cell, respectively. Mean body weights of pregnant rats were decreased at high dose of olaquindox (110 mg/kg) but relative ovary weight, number of corpus lutea, and number of implantation were not changed. Resorption and dead fetus were increased at high dose of olaquindox, and relative ovary weight, the number of corpus lutea and implantation, and sex ratio of male to female were not significantly changed in all dose of olaquindox. Mean fetal and placenta weights were significantly (p < 0.01) decreased in rats of high group. Seven fetuses out of 103 showed external anomaly like bent tail, and 10 out of 114 fetuses showed visceral anomalies at high group. The ossification of sternebrae and metacarpals were significantly (p < 0.01) increased by low and middle dose of olaquindox but it was significantly (p < 0.01) prohibited by high dose of olaquindox. In rats treated with vitamin A, the resorption and dead fetus were increased by high dose. Mean fetal weights were significantly (p < 0.01) increased by low dose but significantly (p < 0.01) decreased by high dose. Thirty four fetuses out of 52 showed external anomaly; bent tail (1), cranioarchschisis (14), exencephaly (14), dome shaped head (22), anophthalmia (15), brcahynathia (10) and others (19). Forty five fetuses out of 52 showed soft tissue anomaly; cleft palate (42/52) and anophthalmia (22/52) by high dose of vitamin A. Sixty one fetuses out of 61 (85.2%) showed skull anomaly; defect of frontal, partial and occipital bone (21/61), defect of palatine bone (52/61) and others (50/61). In summary, we support that vitamin A is strong teratogen based on our micromass and in vivo data, and olaquindox has a weak teratogenic potential in LB cell but not in CNS cell. We provide the in vivo evidence that a high dose of olaquindox could have weak embryotoxic potential in rats.

• The Korea Journal of Herbology
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• v.27 no.4
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• pp.33-44
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• 2012

Objectives : There is a pressing need to determine the clinical and scientific validity of herbal therapies for animal model with atopic dermatitis since some differences in systemic cytokine polarization between in animal model and in patients with atopic dermatitis has been reported. New studies for tang, medicinal herb itself or effective ingradients of medicinal herb showing anti-atopic dermatitis effectiveness are reviewed in terms of cytokine regulation. Methods : Those herbal therapies used to treat atopic dermatitis in animal model were introduced and the expression pattern of cytokine and the activity of mast cell were compared in both animal model and patients with atopic dermatitis. Results : In case of atopic dermatitis in human, there is a biphasic pattern of cytokine expression in atopic dermatitis, with acute skin inflammation associated with a predominance of IL-4 and IL-13 expression from Th2 cells, and chronic inflammation associated with increased IL-5 from Th2-cells and IFN-${\gamma}$ from Th1-cells. However, a pattern of cytokine expression in animal model with atopic dermatitis is not matched well to the biphasic pattern of cytokine expression in patients with atopic dermatitis. In addition, a kind of cytokine is different by animal model with atopic dermatitis. These differences would make herbal medicines, showing their effectiveness on atopic dermatitis, difficult to apply to patients with atopic dermatitis. Conclusion : The pattern of local cytokine expression plays an important role in modulating tissue inflammation, and in atopic dermatitis this pattern depends on the acuity or duration of the skin lesion. Thus, in order to develop medicinal herb itself or effective ingradients of medicinal herb showing anti-atopic dermatitis effectiveness, biphasic pattern of cytokine expression should be considered in animal model with atopic dermatitis.

• Toxicological Research
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• v.26 no.4
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• pp.285-291
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• 2010

Recently, reproductive and neurobehavioral effects of bisphenol A (BPA) have been documented, and thus a review was requested for BPA management direction by the government. Therefore, this study was performed to establish a Korean tolerable daily intake (TDI) for BPA. An expert committee, consisting of specialists in fields such as toxicology, medicine, pharmacology, and statistics, was asked to evaluate BPA health based guidance values (HbGVs). Although many toxicological studies were reviewed to select a point of departure (POD) for TDI, rat and mouse reproductive studies by Tyl et al. (2002, 2006), which were performed according to GLP standards and OECD guidelines, were selected. This POD was the lowest value determined from the most sensitive toxicological test. The POD, a NOAEL of 5 mg/kg bw/day, was selected based on its systemic toxicity as critical effects. An uncertainty factor of 100 including interspecies and intraspecies differences was applied to calculate the TDI. According to the evaluation results, a TDI of BPA for Korean was suggested at 0.05 mg/kg bw/day. In addition, the BPA exposure level based on food consumption by the Korean population was estimated as 1.509 ${\mu}g/kg$ bw/day, and the HI was evaluated at 0.03 when the TDI of 0.05 mg/kg bw/day was applied. This HI value of 0.03 indicated that hazardous effects would not be expected from BPA oral exposures. Although highly uncertain, further studies on low dose neurobehavioral effects of BPA should be performed. In addition, it is recommended that the 'as low as reasonably achievable' (ALARA) principle be applied for BPA exposure from food packaging materials in newborn infants and children.

• Korean Journal of Medicinal Crop Science
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• v.24 no.5
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• pp.408-419
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• 2016

Background: In recent years, adjuvants have received increasing attention owing to the development of purified subunit and synthetic vaccines which are poor immunogens and require additional adjuvants to evoke an immune response. Therefore, immunologic adjuvants have been developed and tested. Plant polysaccharides have been recognized as effective biological response modifiers with low toxicity. Methods and Results: In this study, the polysaccharide from the aboveground part of Astragalus membranaceus Bunge containing immunomodulating arabino-3,6-galactan was evaluated for its hemolytic activity and adjuvant potential in the specific cellular and humoral immune responses to ovalbumin. The polysaccharide from the aboveground part of Astragalus membranaceus Bunge was co-immunized with the purified Vi capsular polysaccharide of Salmonella typhi vaccine in mice. The polysaccharide from the aboveground part of Astragalus membranaceus Bunge did not induce any hemolytic activity or side effects at doses up to $500{\mu}g/m{\ell}$. The concanavalin A-, lipopolysaccharide-, and ovalbumin-induced splenocyte proliferation and serum ovalbumin-specific IgG, IgG1 and IgG2b antibody titers in immunized mice were significantly enhanced by AMA. Pharmacological data revealed that the polysaccharide from the aboveground part of Astragalus membranaceus Bunge increased antigen-specific antibody levels in immunized mice. The polysaccharide from the aboveground part of Astragalus membranaceus Bunge-adjuvanted purified Vi capsular polysaccharide of Salmonella typhi vaccine improved the proliferation of splenocytes and macrophages as well as stimulated cytokine production. Conclusions: These results suggest that the polysaccharide from the aboveground part of Astragalus membranaceus Bunge-adjuvanted vaccines enhanced humoral and cellular immunity and that the polysaccharide from the aboveground part of Astragalus membranaceus Bunge is a safe and efficacious adjuvant candidate suitable for use in prophylactic and therapeutic vaccines.

• Herbal Formula Science
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• v.27 no.4
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• pp.269-284
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• 2019

This study was to investigate whether cultivated ginseng (CG), cultivated wild simulated ginseng (CWG) and cultivated red ginseng (CRG) extracts influences on the obesity. The saponin contents of 3 kinds of ginsengs were analysed by HPLC-ESI-TOF-MS. Total saponin contents were determined in CG on the most contents and since red ginseng has the highest PD (protopanaxadiol type) / PT (protopanaxatriol type) ratio, there may be differences between ginseng, wild ginseng, and red ginseng with respect to their pharmacological effects. Male C57BL/6J mice were fed a normal diet(N), HFD (60% Kcal fat, C), HFD with CG, CWG and CRG extracts (800 mg/kg) for 5 weeks. We observed change of total body weight, degree of hepatic lipid accumulation and immunohistochemical change of GLP-1 and insulin-secreting cells. Also this study attempts to use the physiological analysis method to analyze the changes of blood lipids, insulin and leptin concentration. The change of body weight and size of accumulated lipid droplets in liver lobules decreased in all of the experimental groups than the control(C) group. In the pancreas, the immunohistochemical density of insulin-secreting cells were significantly stronger in the CWG and CRG than C group. The levels of serum insulin and leptin significantly decreased 55.6%, 54.3% respectively in CWG and CRG. The changes of triglyceride, total cholesterol in serum decreased in CRG than the C group. Obesity related CG, CWG and CRG extracts might have contribute to improvement of obesity by regulating the levels of blood lipids and biochemical indicator of fat accumulation.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.22 no.4
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• pp.303-329
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• 2019

Intestinal failure (IF) is the critical reduction of the gut mass or its function below the minimum needed to absorb nutrients and fluids required for adequate growth in children. Severe IF requires parenteral nutrition (PN). Pediatric IF is most commonly due to congenital or neonatal intestinal diseases or malformations divided into 3 groups: 1) reduced intestinal length and consequently reduced absorptive surface, such as in short bowel syndrome (SBS) or extensive aganglionosis; 2) abnormal development of the intestinal mucosa such as congenital diseases of enterocyte development; 3) extensive motility dysfunction such as chronic intestinal pseudo-obstruction syndromes. The leading cause of IF in childhood is the SBS. In clinical practice the degree of IF may be indirectly measured by the level of PN required for normal or catch up growth. Other indicators such as serum citrulline have not proven to be highly reliable prognostic factors in children. The last decades have allowed the development of highly sophisticated nutrient solutions consisting of optimal combinations of macronutrients and micronutrients as well as guidelines, promoting PN as a safe and efficient feeding technique. However, IF that requires long-term PN may be associated with various complications including infections, growth failure, metabolic disorders, and bone disease. IF Associated Liver Disease may be a limiting factor. However, changes in the global management of IF pediatric patients, especially since the setup of intestinal rehabilitation centres did change the prognosis thus limiting "nutritional failure" which is considered as a major indication for intestinal transplantation (ITx) or combined liver-ITx.