• Natural Product Sciences
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• v.9 no.1
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• pp.22-27
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• 2003

This study was designed to investigate the effects of main constituents of Nigella sativa (NS) seed on the survival and CNS responses in experimental animals. The toxicological investigations were conducted for the determination of median lethal doses $(LD_{50})$ of NS seed constituents [i.e. aqueous extract (AE), fixed oil (FO), volatile oil (VO)] and main components of its VO [i.e. thymoquinone (TQ), ${\alpha}-pinene$ (AP) and p-cymene (PC)]. A part of this study includes evaluation NS constituents in the induction of minimal neurological deficit (MND) as a parameter for neurotoxicity using chimney test. In this study, the i.p. $LD_{50}$ values of AE, FO, VO, TQ (suspended In 0.5%CMC), TQ (dissolved in corn oil), AP and PC, were 3020, 3371, 1853, 616.6, 90.3, 1726 and 1523 mg/kg, respectively. All the NS constituents can be considered moderately toxic ($LD_{50}$ ranged from 616.6 to 3371 mg/kg), except the oily solution of TQ, which was very toxic ($LD_{50}$ was 90.3 mg/kg). It appeared that the toxicity of the whole VO is mainly due to its content of TQ and to some extent PC. All the NS constituents induced different degrees of MND at certain dose levels. The median neurotoxic (or sedating) doses $(TD_{50})$ of AE, FO, VO, TQ (suspended in CMC) and AP and PC, were 950, 1403, 306, 88.1, >173 and 368 mg/kg, respectively. TQ was the most potent component in inducing MND, whereas the FO and AE were the least. Neurotoxicity induced by the VO in the chimney test may refer basically to its contents of TQ and to some extent PC and AP.

• Journal of Food Hygiene and Safety
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• v.7 no.2
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• pp.83-89
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• 1992

This study was perfonned to investigate effectiveness eness on the gastritis and gastric lesion with the methanol extract of the flower buds of Eugenio caryophyllata. The extract was fractionated with hexane, chIorofonn, ethyl acetate, butanol, followed by bioassay Oil antigastritis. The ethyl acetate and the buthanol fraction reduced significantly HCI.ethanol induced gastric lesion at the dose of 165 and 215 mg/kg, p.o., respectively. These results may indicate that remarkably.effective are ethyl acetate and butanol fractions in HCI-ethanol induced gastric lesion. Howeever, the fractions didn't exhibit any inhibition of gastric secretion and acid output. The buthanol fraction reduced significantly the acetic acid induced ulcer at a daily dose of 215 mg/Kg, p.o., given for 10 days. These result showed considerable inhibit of acetic acid induced ulcer without inhibition of indomethacin induced gastric lesion. The methanol extract showed low acute toxicity with minimum lethal dose of more than 3000 mg/kg, p.o. in mice. In conclusion, Eugenia F10s exhibited antigastric activity which might be attributable to inhibition of gastric secretion. It is indicated that activie component may be present in the buthanol fraction.

• Journal of Pharmacopuncture
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• v.17 no.3
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• pp.50-56
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• 2014

Objectives: Mountain ginseng pharmacopuncture (MGP) is an extract distilled from either mountain cultivated ginseng or mountain wild ginseng. This is the first intravenous injection of pharmacopuncture in Korea. The word intravenous does not discriminate between arteries, veins, and capillaries in Oriental Medicine, but only the vein is used for MGP. The aim of this study is to evaluate the intravenous injection toxicity of MGP through a single-dose test in Sprague-Dawley (SD) rats. Methods: Male and female 6-week-old SD rats were injected intravenously with MGP (high dosage of 20 mL/kg or low dosage of 10 mL/kg). Normal saline was injected into the rats in the control group by using the same method. After the rats has treated, we conducted clinical observations, body-weight measurements and histological observations. Results: In this study, no mortalities were observed in any of the experimental groups. Also, no significant changes by the intravenous injection of MGP were observed in the body weights, or the histological observations in any of the experimental groups compared to the control group. The lethal dose for intravenous injection of MGP was found to be over 20 mL/kg in SD rats. Conclusion: Considering that the dosage of MGP generally used each time in clinical practice is about 0.3 mL/kg, we concluded with confidence that MGP is safe pharmacopuncture.

• Journal of Acupuncture Research
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• v.36 no.3
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• pp.147-153
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• 2019

Background: The aim of this study was to investigate the safety and analgesic effects of Datura Flos pharmacopuncture (DFP). Methods: The analgesic effects of DFP were assessed using mechanical (hot plate), chemical (formalin test), and thermal (von Frey filament test) pain tests. Forty male Sprague Dawley rats were assigned randomly into DFP (75 mg/kg, 150 mg/kg), lidocaine 0.5%, or normal saline group for treatment on Kl3. Gross pathology, histopathology, biochemistry and hematology were performed. Results: In the hot plate test, DFP at a high dose (HDDFP; 150 mg/kg) produced a significant analgesic effect, at 10 and 20-minutes post injection (p < 0.01). Low dose DFP (LDDFP; 75 mg/kg) also showed an analgesic effect at 10 minutes post injection (p < 0.01). In the formalin test, HDDFP produced an analgesic effect, for 0-10 and 10-20 minutes (p < 0.01) post treatment, whereas LDDFP showed analgesic effects between 10-20 minutes (p < 0.05). In the von Frey filament test, DF-H produced an analgesic effect, 10 (p < 0.01) and 20 minutes post treatment (p < 0.05). LDDFP showed analgesic effect at 10 minutes (p < 0.05). In the acupuncture response test, HDDFP produced an analgesic effect at 10 minutes post treatment (p < 0.05). DF-H did not cause any anatomical changes to the liver or kidney and there were no abnormalities in biochemistry or hematology. Conclusion: DF-H was not toxic and provided short term analgesia, suggesting it may be useful in the management of pain.

• Toxicological Research
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• v.29 no.2
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• pp.91-98
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• 2013

Armeniacae semen (AS) has been considered a toxic herb in the Korean medicine as it contains hydrogen cyanide and amygdalin, especially in its endocarp. Therefore, prebrewed AS that is devoid of endocarp has been traditionally used. In the present study, amygdalin content of the prebrewed AS was significantly lower ($2.73{\pm}0.32{\mu}g/ml$; p<0.01) than the content in the extract that contained the endocarps ($28.50{\pm}6.71{\mu}g/ml$); amygdalin content corresponded to 10% of the extract in the present study. Because of single oral dose toxicity of prebrewed AS according to the recommendation of Korea Food and Drug Administration Guidelines (2009-116, 2009), which was based on single oral dose toxicity study of prebrewed AS, mortality due to toxic principles was significantly reduced. In this study, 2,000 mg/kg of prebrewed AS led to death of 1 female rat and 1 male rat at the end of 2 hr of administration. Based on these results, the 50% lethal dose in both male and female rats was determined to be 9279.5 mg/kg. Seizure, loss of locomotion, and increases in respiration and heart rate were observed as prebrewed AS treatment-related toxicological signs; these signs were restrictedly manifested in the prebrewed AS (2,000 mg/kg)-treated rats. In addition, no changes were observed in body weight, organ weight, gross features, and histopathological parameters with 2,000 mg/kg of AS in both male and female rats. These findings serve as direct evidence that amygdalin in AS is the toxic principle, which can be reduced by the traditional prebrewing method involving the exclusion of endocarp.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.3
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• pp.1-9
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• 2015

Objectives To evaluate Shinbaro Pharmacopuncture safety through analysis of potential single-dose intramuscular toxicity of Sinbaro Pharmacopucture in SD rats and Beagle dogs. Methods Single-dose intramuscular toxicity of Shinbaro Pharmacopuncture was assessed in accordance with Korea Food and Drug Administration Guidelines for toxicity testing of Medicinal Products. The SD rats were treated intramuscularly with Shinbaro Pharmacopuncture at doses of 0, 4.6, 9.2, and 18.5 mg/kg, respectively. The Beagle dogs were treated intramuscularly with Shinbaro Pharmacopuncture at doses of 2.3, and 4.6 mg/kg, respectively, and after 3 days, the procedure was repeated a second time at doses of 0.6, and 1.2 mg/kg, respectively, for toxicity testing. Mortality, change in body weight, and necropsy findings were examined for the study period. Results There were no mortalities, general symptoms, or body weight changes in the SD rats. While pyelectasis of the left kidney was observed in a male rat in the 4.6 mg/kg administration group, natural occurrence is common, and does not appear to be related with the test substance. No mortalities were observed in the Beagle dogs. In assessment of general symptoms, a female dog in the 9.2 mg/kg group displayed body weight decrease due to leftover food, but the change in body weight was within the normal range seen at 6~7 months, and the necropsy findings were not significant. The toxicity of the test substance appears to be minimal. Conclusions The results suggest that the lethal dose 50 ($LD_{50}$) and approximate lethaldose (ALD) value in single intramuscular administration of Shinbaro Pharmacopuncture in SD rats and Beagle dogs are higher than 18.5 mg/kg.

• Korean Journal of Medicinal Crop Science
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• v.28 no.5
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• pp.339-346
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• 2020

Background: Cnidium officinale Makino have been used in traditional medicine in Northeast Asia. Although gamma-ray mutagenesis has been used to develop breeding resources with novel characteristics, research on the radiation sensitivity of C. officinale Makino is limited. Hence, the optimal gamma-ray dosage for mutation breeding in C. officinale Makino was investigated. Methods and Results: Seedstocks were exposed to doses of gamma rays (5 Gy - 50 Gy), and subsequently planted in a greenhouse. After 30 days of sowing, the survival rates and growth decreased rapidly at doses above 20 Gy, while all individuals died at 50 Gy. The median lethal dose (LD₅₀) was 25.65 Gy, and the median reduction doses (RD₅₀) for plant height, number of stems, and fresh weight were 12.81, 9.32, and 23.26 Gy, respectively. Post-irradiation levels of malondialdehyde (MDA), peroxidase (POD), and chlorophyll in the aerial parts of the plant were quantified using spectrophotometry. Relative to the controls, the levels of MDA and POD increased, while the level of chlorophyll decreased at doses ≥ 10 Gy, indicating cellular damage. Conclusions: A dose of 20 Gy was found to be optimal for mutation breeding in C. officinale Makino.

• The Korean Journal of Mycology
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• v.46 no.3
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• pp.295-306
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• 2018

In the present study, we compared the effects of 50% ethanolic extracts of Chinese and Korean Wolfiporia cocos (CPE and KPE) on in vitro lipid accumulation in 3T3-L1 cells and their anticancer activities in Sarcoma 180 cells. We further compared the anticancer activities and the 50% inhibitory concentrations ($IC_{50}$) of CPE with KPE with cultivated for one and two years in a landfill and a facility (LPE and FPE), respectively. In addition, the single oral dose toxicities of CPE and KPE were evaluated in mice. Lipid accumulation was inhibited after 48 hours, in CPE and KPE treated 3T3-L1 cells; however, no significant difference was observed between CPE and KPE in their lipid accumulation inhibitory activities. The anticancer activity of KPE was higher than that of CPE at $300{\mu}g/mL$ (p<0.05), revealing the possibility of an auxiliary biological means for origin identification. The anticancer activities of LPE and FPE were significantly stronger than that of CPE (p<0.05) but there was no difference between extracts from one- and two-year-old W. cocos, irrespective of the cultivation method. In single oral dose toxicity tests, CPE and KPE did not induce mortality during the 14-day observation. Thus, the 50% of lethal dose ($LD_{50}$) of CPE and KPE were estimated to be higher than 2,000 mg/kg. Taken together, our results indicate that the anticancer assay could be an auxiliary means of identifying the origin of W. cocos. In addition, artificial cultivation could be an alternative way to reduce the import of W. cocos. Lastly, 50% ethanolic W. cocos extracts could be potential candidates for obesity and cancer managements.

• Korean Journal of Veterinary Research
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• v.53 no.1
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• pp.29-35
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• 2013

To develop a live vaccine candidate using an attenuated strain of Salmonella Typhimurium (ST), biochemical properties, plasmid profile, PFGE patterns and pathogenic analysis of the ST isolate were carried out after sequential passage of the ST isolate in porcine neutrophils. By the passage, the ability of the neutrophil-adapted isolate to utilize d-xylose was lost, while the ability of the strain to ferment trehalose was delayed after 2 or more days of the culture. Also, changes including deletion of the gene fragments were observed in PFGE analysis of the neutrophil-adapted isolates. Two plasmids, 105kb and 50kb, were cured in the strain passaged over 15 times in porcine neutrophils. The 50% of lethal dose ($LD_{50}$) of the parent strain was changed from $1{\times}10^5\;LD_{50}$ to $6{\times}10^6\;LD_{50}$ by the passage in intraperitoneal injection of the strains into mice. These results suggested that bacterial genotypic and phenotypic responses might be globally altered depending on the inside environment of neutrophils.

• Journal of Korean Medicine Rehabilitation
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• v.31 no.1
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• pp.95-108
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• 2021

Objectives This study was conducted to investigate the beta-glucan, ginsenoside content, antioxidant activity and safety of modified Kyungohkgo added to Sparassis crispa and Hericium erinaceum. Methods The marker compounds contents, antioxidant activity and safety of modified Kyungohkgo were tested. The contents of beta-glucan and ginsenoside Rb1, Rg1, and Rg3 marker compounds were measured, the antioxidant activity was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, and a safety test was conducted via single dose toxicity assessment. Results Analyzing the contents of marker compounds showed 351.75 mg/g of beta-glucan, 0.0327 mg/g of ginsenoside Rb1 and 0.0802 mg/g of ginsenosai Rg3. In the DPPH free radical scavenging activity, the inhibition concentration 50% of modified Kyungohkgo was 0.2880%. The scavenging activity of modified Kyungohkgo was 5.49% activity at 0.05% concentration, 89.66% activity at 0.5% concentration, 94.68% activity at 1% concentration, and 96.06% activity at 5% concentration. In the single dose toxicity test of modified Kyungohkgo, a dose of 2,000 mg/kg B.W. 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 B.W. or higher for both females and males. Conclusions The results of the experiment on modified Kyungohkgo showed that the marker compounds contents were beta-glucan and ginsenoside Rb1 and Rg3, that antioxidant activity was observed through the DPPH free radical scavenging activity, and safety was confirmed through the single dose toxicity assessment.