• Microbiology and Biotechnology Letters
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• v.24 no.5
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• pp.624-629
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• 1996

The ethanol extracts from Angelica gigas Nakai and Angelica acutiloba Kitagawa were fractionated to diethyl ether and aqueous partitions. Both partitions had strong antimutagenic effect on the MNNG (N-methyl-N-nitro-N-nitrosoguanidine) by Ames mutagenicity test. Diethyl ether fractions exhibited the greatest antimutagenic effect suppressing the mutagenicity of MNNG with inhibition of 78-80%. The ethanol extracts from both species showed the inhibitory effect on the growth of several human cancer cell lines. Especially, the diethyl ether fraction from ethanol extracts was most effective on human hepatocellular carcinoma cells, inhibiting 90-95% of cell growth. However, the aqueous fractions had least inhibition activity on many cancer cells. There was little cytotoxicity on human normal liver cell by ethanol extracts. Diethyl ether fraction from Angelica gigas Nakai ethanol extract had cytotoxicity less than 20% on human normal liver cells, compared with that from Angelica acutiloba Kitagawa ethanol exract. The adding of 0.5 (g/l) of diethyl ether fractions of Angelica gigas Nakai or Angelica acutiloba Kitagawa increased immune activity by enhacing human B and T cells up to three to four times. It was proven that diethyl ether fraction (0.7 g/1) from Angelica gigas Nakai could control blood pressure by suppressing angiotensin converting enzyme activity up to 98%. From TLC, it was appeared that both of diethyl ether partitions had umbelliferon, known to one of active substances from Angelica gigas Nakai and Angelica acutiloba Kitagawa.

• 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.

• Toxicological Research
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• v.3 no.1
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• pp.15-26
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• 1987

The mutagenicity of pranoprofen, a new antiinflammatory agent primarily used in Japan, was evaluated by employing several different methods such as the Ames test, micronucleus test, and the sister chromatid exchange test. For the Ames test, various doses of pranoprofen (5 and 1 mg, 100, 10, and 1 ${\mu}$g per plate) were applied, with or without the mammalian liver S-9 fraction, to the S. typhimurium LT2. For the micronucleus test, 24 hours after administering the various doses of pranoprofen (200, 100, and 50 mg/kg) to male mice by aral intubation, the femura of each group were isolated and the bone marrow samples were prepared. The micronucleated red cells and the ratio of the polychromatic versus the normochroomatic cells were counted. For the sister chromatid exchange test, the maximal non-cytotoxic concentrations (10 to 0.1 mM pranoprofen) were applied to the culture media of the Chinese Hamster Ovary (CHO) cells for 24 hrs. The numbers of revertant colonies did not increase with the increasing doses of pranoprofen when teseted with various strains of S. typhimurium. In the micronucleus test employing mice, the pranoprofen was identkfied to be a non-clastogen and a non-spindle poison. In the sister chromatid exchange test employing the cultured CHO cells, the pranoprofen did not increase the incidences of chromosomal abnormality. Based on these results, pranoprofen was found to have no mutagenic activity.

• Journal of Life Science
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• v.17 no.6 s.86
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• pp.791-797
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• 2007

We studied the inhibitory effect of solvent fractions from doenjang on mutagenicity using Salmonella typhimurium TA100 in Ames test. We also investigated the effect of solvent fractions from doenjang on the growth of tumor cells and the production of interleukin-2 (IL-2). The treatment of dichlorormethane and ethylacetate fractions (2.5 mg/assay) from doenjang to Ames test system inhibited aflatoxin B$_1$ (AFB$_1$) induced mutagenicity by 96% and 97%, respectively, and showed a higher antimutagenic effect than other solvent fractions. In case of N-methyl-N'-nitro-N-nitrosoguamidine (MNNG) induced mutagenicity, the ethylacetate fraction showed the highest inhibitory effect (by 75%) among the other sol-vent fractions, although the inhibitory effect was not stronger compared to AFB$_1$ induced mutagenicity. The treatment of dichloromethane and ethylacetate fractions markedly inhibited the growth of Yac-1 (by 80% and 94%, respectively) and sacroma-180 cancer cells (by 60% and 96%, respectively) after 4 days of incubation at 37${\circ}$C. To elucidate the immunological mechanism of antitumor activity of doenjang, spleen cells of Balb/c mouse were exposed to the dichloromethane and ethyl-acetate fractions for 24 hours at 37${\circ}$C . The culture supernatants following the treatment of djchloromethane and ethylacetate factions to spleen cells increased the production of IL-2. These results indicated that the anticarcinogenic effect of doenjang was mediated by the production of IL-2.

• Journal of Pharmacopuncture
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• v.19 no.3
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• pp.213-224
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• 2016

Objectives: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. Methods: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. Results: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. Conclusion: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.

• Journal of Nutrition and Health
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• v.32 no.1
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• pp.110-117
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• 1999

Free radicals formed during the metabolism of environmental chemicals are known to induce mutagenicity, while different types of antioxidants suppress this event. The purpose of this study was to determine the antioxidative and antimutagenic effects of soybean saponins, and to examine the relationship between these two effects for the elucidation of mechanisms involved in the anticarcinogenicity of soybean saponins. Also, antioxidative and antimutagenic effects of soybean saponins were compared with those of kinown antioxidants. For the measurement of antioxidative capacity, soybean saponins, L-ascorbic acid, $\alpha$-tocophoerol, and BHT at concentrations between 005 and 1.0mg/ml were tested for their ability to donate hydrogens and to reduce the formation of thiobarbituric substances(TBARS). Antimutagenic activity was examined using the Ames salmonella test system at concentrations of 600, 900 or 1200ug/ml. Study results showed soybean saponins and all of the other antioxidants tested possessed dose-dependent antioxidative activities. The ability of hydrogen-donation to DPPH was in the order of L-ascorbic acid>$\alpha$-tocopherol=>BHT>soybean saponins. TBARS formation was also inhibited by these compounds, in the order of BHT>$\alpha$-tocopherol=L-ascorbic acid>soybean saponins. Soybean saponins and other antioxidants also showed antimutagenicity in a dose-dependent manner. Especially, soybean saponins and BHT were excellent antioxidants compounds, inhibiting near 80% of the mutagenic effects at a concentration of 1200ug/ml. The correlation coefficients between antioxidative capacity and antimutagenicity for each compund was statistically significant at p<0.05. These results indicate that soybean saponins possess antioxidative and antimutagenic capacities. Also, antimutagenicity of saponins and other antioxidats is partly due to their antioxidative activities.

• Molecular & Cellular Toxicology
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• v.4 no.4
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• pp.285-292
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• 2008

Crocin is one of the major components of gardenia fruit and saffron which are widely used as natural food colorants and as traditional Chinese medicines. However, the genotoxicity data on crocin are not sufficient for safety evaluation. The purpose of this study was the examination of the genotoxicity on crocin from gardenia yellow in bacterial and mammalian cells, using various genotoxic battery testing assays and the influence of crocin on methyl methanesulfonate (MMS) and ${H_2}{O_2}$-induced DNA damage in vitro, using single cell gel electrophoresis (comet) assay. From results, no considerable mutagenicity and clastogenicity were seen in bacteria and mammalian cells treated with crocin, by Ames test, chromosomal aberration assay, ${tk}^{+/-}$ gene forward mutation assay and comet assay. And, post-treatment with crocin significantly suppressed ${H_2}{O_2}$-induced DNA damage in a dose-dependent manner. In conclusion, the findings of the present study and other previous observations indicate that crocin has no genotoxic potential. And it showed that crocin clearly repressed the genotoxic potency of ${H_2}{O_2}$. These results suggest that anti-oxidative effects of crocin may be involved in the protective effects of DNA damage.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.4
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• pp.410-415
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• 2008

This study was performed to observe the antimutagenic and cytotoxic activities of methanol extract of kochujang added with sea tangle and deep sea water salts (SDK) and kochujang added with sea tangle (SK) using the Ames test and SRB assay, respectively. The direct antimutagenic effect of SDK and SK methanol extracts were examined by Ames test using Salmonella Typhimurium TA98 and TA100. In the Ames test, methanol extract of SDK and SK alone did not exhibit mutagenicity and most of the samples showed high antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). Methanol extract of SDK ($200{\mu}g$/plate) showed approximately 71.4% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain; whereas 56.1% and 83.6% inhibitions were observed on the mutagenensis induced by 4NQO and MNNG against TA100 strain. The cytotoxic effects of SDK and SK increased with increasing sample concentration against human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human breast adenocarcinoma (MCF-7), human stomach adenocarcinoma (AGS), and human lung carcinoma (A549). The SDK at the concentration of 1 mg/ml showed cytotoxicities of 61.5%, 61.3%, 51.4%, 57.9% and 77.7% against HeLa, Hep3B, MCF-7, AGS and A549, respectively. In contrast 1 mg/ml treatment of SDK and SK methanol extract had only $2{\sim}38%$ cytotoxicity on human transformed primary embryonal kidney cell (293).

• The Korean Journal of Food And Nutrition
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• v.25 no.4
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• pp.888-896
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• 2012

Considering the dearth of information regarding the medicinal properties of Luffa cylindrica, we assessed the antioxidative, antimutagenic and hyperplasia inhibitory activity of cancer cells from Luffa cylindrica extracts by employing biological and biochemical assays. Ethanol extracts of Luffa cylindrica inhibited MDA-BSA (malondialdehyde-bovine serum albumin) conjugation reaction ($66.38{\pm}2.65$), DPPH (1,1-diphenyl-2-picryl-hydrazyl) radical production ($60.13{\pm}0.42$) and lipid peroxidation ($56.04{\pm}3.24$). In this study, Luffa cylindrica is believed to exert possible antioxidative effects. The direct and indirect antimutagenic effects of the ethanol extracts of Luffa cylindrica were examined by the Ames test using Salmonella typimurium TA98 and TA100. The inhibitory effects on indirect and direct mutagenicity shows an weak tendency, particularly in direct mutagenicity mediated by 2-nitrofluorene in Salmonella typimurium TA98 ($5.82{\pm}5.74$) and in indirect mutagenicity mediated by 2-anthramine in Salmonella typimurium TA100 ($5.76{\pm}2.15$). The ethanol extracts of Luffa cylindrica on cancer cell hyperplasia inhibitory activity via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay exerted cytotoxic effects on Hela cells ($55.83{\pm}3.83$) and MCF-7 cells ($33.03{\pm}2.09$), which were used in this study. Based on these results, it believed that the ethanol extracts of Luffa cylindrica have antioxidative capacities as well as hyperplasia inhibitory activity of cancer cells. Furthemore, Luffa cylindrica is a candidate for the prevention and dietetic treatment of chronic diseases and for the development of functional food.

• Natural Product Sciences
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• v.4 no.2
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• pp.105-114
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• 1998

The antimutagenic activity of a methanol extract of Ecklonia stolonifera (Laminariaceae) against aflatoxin $B_1\;(AFB_1)$ was demonstrated with the Salmonella typhimurium assay. The numbers of revertants per plate decreased significantly when this extract was added to the assay system using S. Salmonella typhimurium TA100. The methanol extract also exhibited significant inhibitory effects on the micronuclei formation in mouse peripheral blood reticulocytes and the DNA damage in mouse spleen lymphocytes induced by N-methyl-N-nitrosourea (MMU) and benzo(a)pyrene (B(a)P). The MeOH extract was then sequentially partitioned with $CH_2Cl_2,\;CH_2Cl_2$ insoluble intermediate, EtOAc, n-BuOH, and $H_2O$. All fractions possessed antimutagenic activity but the $H_2O$ fraction was inactive. Among active fractions, the EtOAc and $CH_2Cl_2$ insoluble intermediate fractions showed the highest activity. Column chromatography using $SiO_2$ and Sephadex LH-20 yielded phloroglucinol from the EtOAc fraction. Phloroglucinol also demonstrated significant antimutagenic activity, and inhibitory effects on the micronuclei formation in mouse peripheral blood reticulocytes and DNA damage in mouse spleen lymphocytes induced by MMU and B(a)P.