• The Journal of Internal Korean Medicine
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• v.39 no.5
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• pp.973-983
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• 2018

Objectives: We report a case of traditional Korean medicine (TKM) treatment for skin side effects after taking afatinib (Giotrif$^{(R)}$). Methods: A 62-year-old female who was diagnosed with non-small cell lung cancer stage 4 (T4N2M1b) and was on treatment with afatinib (29.56 mg/day for 4 months) complained of skin toxicity as a side effect. For 16 admission days, the patient was treated with acupuncture, moxibustion, and herbal medicine (oral decoction and external ointment). Results: Improvement of skin toxicity was measured by a numeric rating scale. In addition, Quality of life (QOL) was measured using EORTC Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire, 13-item lung cancer-specific module (EORTC QLQ-LC13) Developed by the European Organization for Research and Treatment of Cancer (EORTC). Tumor size and carcinoembryonic antigen (CEA) were also examined during follow up. Conclusions: After a combined TKM treatment, skin toxicity symptoms and quality of life scales were significantly improved with no side effects. The tumor size was not changed on computed tomography during follow-up period. CEA levels were decreased.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.8
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• pp.975-982
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• 2007

The purpose of this study was to investigate repeated-dose toxicity in male and female rats orally administered with Pediococcus pentosaceus MD1, an anti-Helicobacter pyroli producing lactic acid bacteria isolated from kimchi. Sprague-Dawley rats were divided into 4 groups, 10 animals in each group. The test article was administered once daily by gavage to rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg for 4 weeks. No test article-related deaths and clinical findings in both sexes of rats during the study period were resulted. In addition, no differences were found between control and treated groups in body weight changes, food intake consumption and water consumptions. Hematological parameters, serum biochemical analysis and any other findings did not also show any significant or dose-dependent alterations. There were no alterations in absolute and relative organ weights by the administration of Pediococcus pentosaceus MD1. These results suggest that no-observed-adverse-effect level (NOAEL) of Pediococcus pentosaceus MD1 is considered to be more than 2 g/kg in male and female rats.

• Food Science and Preservation
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• v.20 no.1
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• pp.121-126
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• 2013

The present study was carried out to investigate the in vivo single-dose acute toxicity of Leuconostoc citreum GR1 (Leuc. citreum GR1), a lactic acid bacteria isolated from kimchi, in ICR male and female mice. The test article was orally administered once to both sexes of mice. The mortalities, clinical findings, autopsy findings, and body weight changes were monitored daily for two weeks. The male and female mice were gavaged with Leuc. kimchi GR1 of four doses (625, 1,250. 2,500 and 5,000 mg/kg). The oral $LD_{50}$ of Leuc. citreum GR1 was considered higher than 5,000 mg/kg. No significant changes in the general conditions, body weights, clinical signs and presence of gross lesions were observed in both sexes of mice to whom Leuc. citreum GR1 was administered orally. The results indicated that the 5,000 mg/kg dose of Leuc. citreum GR1 showed no adverse effect.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.2
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• pp.1-17
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• 2022

Objectives This study was conducted to investigate the beta-glucan & ginsenoside content, antioxidant activity, anti-inflammatory effect and safety of herbal medicine mix. Methods The marker compounds contents, antioxidant activity and safety of herbal medicine mix were tested. The contents of beta-glucan and ginsenoside Rg3 were measured, the antioxidant activity was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, anti-inflammatory and a safety test was conducted via single dose toxicity assessment. Results Analyzing the contents of marker compounds showed 362.3 mg/g of beta-glucan, and 0.4184 mg/g of ginsenoside Rg3. In the DPPH free radical scavenging activity, the IC50 of herbal medicine mix, was 0.146%. The scavenging activity of herbal medicine mix was 88.28% activity at 0.5% concentration, and 90.61% activity at 5% concentration. In the lipopolysaccharides (LPS) anti-inflammatory test, the herbal remix showed a significant decrease in tumor necrosis factor-alpha (TNF-𝛼) and interleukin-6 (IL-6) compared to the LPS-induced group. In the single dose toxicity test of herbal medicine mix, a dose of 2,000 mg/kg body weight (BW) was set at its highest capacity and observed after oral administration to female and male rats. No toxicological findings were recognized. It was observed that the resulting lethal dose can be set to 2,000 mg/kg BW or higher for both females and males. Conclusions The results of the experiment on herbal medicine mix showed that the marker compounds contents were beta-glucan and ginsenoside Rg3, that antioxidant activity was observed through the DPPH free radical scavenging activity, anti-inflammatory effect was observed through TNF-𝛼 and IL-6 measurement, and safety was confirmed through the single dose toxicity assessment.

• Journal of the Korean Applied Science and Technology
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• v.38 no.6
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• pp.1466-1475
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• 2021

Compound K (20-O-β-(_D-glucopyranosyl)-20(S)-protopanaxadiol) is an active ingredient of ginsenosides. Compound K has been known to produce from biotransformation by β-glucosidase action of human intestinal microbes after oral admistration of ginseng. We have investigated the cytotoxicity of compound K obtained from bio-converted ginseng extract. As a result, compound K showed no significant cytotoxicity in the concentration of 0.001 to 1 ㎍/mL and inhibited the production of TNF-α, MCP-1, IL-6 and NO in RAW 264.7 cells induced by LPS inflamation. In the same concentration, HaCaT cells induced by inflammation with TNF-α and IFN-γ decreased IL-8 production due to compound K treatment. In the brine shrimp lethality assay, the LC₅₀ of compound K was 0.37 mg/mL indicating some toxicity, but the bioconverted product containing 35% compound K showed relatively low toxicity with an LC₅₀ of 0.87 mg/mL. These results suggest that the compound K enriched extract is a potential functional material for acne relief cosmetic products.

• Journal of Environmental Health Sciences
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• v.49 no.1
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• pp.22-29
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• 2023

Background: The existing research results on the combined toxicity of these pollutants using mammals, such as rodents, are insufficient, especially in relation to changes in the immune system. Objectives: This study aims at evaluating the cellular immune response to PE-MPs solely or when combined with Pb, which possess excellent adsorption capacity with PE-MPs and is commonly co-exposed in our daily lives. Methods: The study investigated the cellular immune function of 9-week ICR mice with 28 days exposure to PE-MPs (2 mg/mouse/day) and Pb (0.1 mM in distilled water) individually and in combination. PE-MPs were administered via gastric intubation while the lead intake was conducted via the oral drinking water route. Cellular immunity was evaluated by analyzing the production for T_H1 cytokines namely, TNF-α and IFN-𝛾 and T_H2 cytokines, IL-4 and IL-6 in culture supernatants from polyclonally activated splenic mononuclear cells ex vivo. Results: Both the PE-MPs only and the PE-MPs+Pb exposure group revealed an increased T_H1 response with elevated TNF-α and IFN-𝛾 levels and downregulated T_H2 response with low IL-4, and IL-6 production levels compared to the control group. Furthermore, an increased IFN-𝛾/IL-4 ratio was found in the PE-MPs only and PE-MPs+Pb exposure groups, which indicated the skewedness to T_H1 response. Meanwhile, reduced blood hemoglobin levels and increased levels of IL-4, the dominant T_H2 cytokine in the Pb-only exposure group, were observed. Conclusions: Our current findings on the predominance of T_H1 immune response in the PE-MPs and PE-MPs+Pb groups suggest that PE-MPs could be responsible for the predominant induction of the cellular immune changes. This finding could be used as an important landmark in research related to T_H1 predominance, such as autoimmune diseases. It suggests that additional research on immune modulation using longer exposure durations or the same exposure route is required to elucidate stronger findings.

• Natural Product Sciences
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• v.29 no.2
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• pp.74-82
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• 2023

Nepeta sibirica L. or Siberian catmint is a medicinal plant species used in Mongolian traditional medicine for curing human different disorders and veterinary practices. The previous study of the whole plant concentrated on the determination of its essential oil composition and reported that the major ones are sesquiterpenes, including nepetalactone. The aim of this study was to reveal a new biological activity of the above-ground parts of N. sibirica L. and compare the activity of different extracts correlating with the content of biologically active compounds and evaluate their toxicity. For this purpose, anti-oxidative and acetylcholinesterase inhibitory activities of the above-ground parts of N. sibirica L. aqueous and ethanol (EtOH) (40%, 70%) extracts were assayed spectrophotometrically. The aqueous extract showed positive anti-oxidative activity by both tested DPPH and FRAP assays with IC₅₀ 134.24 ± 1.42 mg/mL and FRAP value 1385.15 ± 8.12 µmol/L at 200 ㎍/mL, in contrast to 40% and 70% EtOH extracts. The 70% EtOH extract presented the highest acetylcholinesterase inhibitory activity (IC₅₀ 77.29 ± 0.38 mg/mL) followed by 40% EtOH extract (176.72 ± 0.35 mg/mL) and aqueous extract (275.41 ± 0.23 mg/mL). Total phenolics were found to be gallic acid equivalent, % 3.74 ± 0.05 (70% EtOH), 3.94 ± 0.04 (40% EtOH), and 3.79 ± 0.16 (aqueous), whereas the total flavonoids as a rutin equivalent, % as 2.01 ± 0.12, 1.44 ± 0.17 and 1.99 ± 0.02, each. The aqueous extract showed the best anti-oxidative and lowest activity against the acetylcholinesterase; however, the 70% EtOH extract showed the opposite effects than that of the aqueous. No mortality incidence was visible at various doses, indicating that the oral median lethal dose of aqueous and 70% EtOH extracts were considered greater than 5000 mg/kg. N. sibirica L. belongs to the non-toxic category of the OECD 423 classification.

• The Journal of Internal Korean Medicine
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• v.30 no.2
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• pp.338-354
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• 2009

Objective : Gamijihwang-tang(GJT) has been used as a therapeutic agent for hyperlipidemia in oriental medicine for several years. This study was performed to investigate the effects of GJT on hyperlipidemia in rats using diverse biological methods. Method : Hyperlipidemia was induced by a hyper-lipidemic diet fed for 4 weeks. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, and glucose were measured in the serum after an oral administration of GJT. Lipid peroxidase, SOD, catalase, ACAT, and HMG-CoA were measured in liver after oral administration of GJT. Result: 1. GJT showed safety against cytotoxicity and toxicity in liver. 2. GJT significantly decreased rat's body and liver weight. 3. GJT significantly decreased serum total cholesterol and LDL-cholesterol, but increased serum HDL-cholesterol. 4. GJT significantly decreased serum triglyceride and glucose. 5. GJT significantly decreased lipid peroxidation and increased SOD and catalase in liver. 6. GJT significantly decreased ACAT and HMG-CoA reductase of cholesterol manifestation in liver. Conclusions : These results suggest that GJT might be effective in treatment and prevention of hyperlipidemia.

• Korean Journal of Pharmacognosy
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• v.42 no.4
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• pp.341-347
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• 2011

The neuroprotective effects of herbal ethanol extracts from Gynostemma pentaphyllum (GP-EX) in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease treated with L-DOPA were investigated. Rats were prepared for the Parkinson's disease model by 6-OHDA-lesioning for 14 days. The rats were then treated with L-DOPA (10 and 20 mg/kg) with or without the oral administration of GP-EX (30 mg/kg, daily) for 28 days. L-DOPA (20 mg/kg) treatment for 28 days enhanced dopaminergic neuronal cell death in 6-OHDA-lesioned rat groups, but L-DOPA (10 mg/kg) did not. However, the oral administration of GP-EX (30 mg/kg) for 28 days ameliorated the enhanced neurotoxic effects induced by chronic L-DOPA treatment in 6-OHDA-lesioned rat groups by increasing tyrosine hydroxylase (TH)-immunohistochemical staining and the number of TH-immunopositive cells surviving in the substantia nigra. In addition, GP-EX administration (30 mg/kg) for 28 days recovered the levels of dopamine and norepinephrine of the striatum in 6-OHDA-lesioned rat groups, which were markedly reduced by L-DOPA treatment (20 mg/kg). GP-EX (30 mg/kg) did not produce any signs of toxicity, such as weight loss, diarrhea, or vomiting in rats during the 28-day treatment period. These results suggest that GP-EX has protective functions against chronic L-DOPA-induced neurotoxic reactions in dopaminergic neurons in the 6-OHDA-lesioned rat model of Parkinson's disease. Therefore, GP-EX may be beneficial in the prevention of adverse symptoms in parkisonian patients.

• Journal of Veterinary Clinics
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• v.27 no.2
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• pp.163-169
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• 2010

To evaluate of oral toxicity of Epimedium koreanum nakai (EKN) water extract, three doses of EKN water extract (10, 100 and 1000 mg/kg/day) were administered to healthy Sprague-Dawley rats for 4 weeks. The results showed that there are no abnormal signs during the experimental period. The weights of testis and epididymis were increased dose-dependently, but seminal vesicle was decreased compared with control group. In hematology and serum chemistry, changes were observed within the normal ranges. In histological finding, slight to moderated changes were found but those were commonly or rarely encountered in the normal rats. These results suggest that no observed adverse effect level (NOAEL) of the oral application of EKN was considered to be more than 1000 mg/kg in SD rats under the conditions employed in this study.