Comparative sub-chronic toxicity studies in rats of two indistinguishable herbal plants, Cynanchum wilfordii (Maxim.) Hemsley and Cynanchum auriculatum Royle ex Wight.

Sub-chronic toxicity studies using rats have been conducted for Cynanchum wilfordii (Maxim.) Hemsley (CW) and Cynanchum auriculatum Royle ex Wight (CA). CW water extract didn't show any adverse effects whereas administering CW powder decreased body weights in complication with decreased food consumptions. In the case of CA water extract, triglyceride and absolute/relative liver weights were elevated and vacuolation was observed in liver. Treated CA powder in male rats increased alanine aminotransferase and aspartate aminotransferase and induced single cell necrosis and multinucleated hepatocyte in liver. As for female rats, increased absolute/relative weights and hypertrophy/vacuolation in adrenal glands and vacuolation in ovaries were observed when administered CA powder. In conclusion, no observed adverse effect level (NOAEL) of CW water extract was over 5000 mg/kg/day, while NOAEL of CW powder was 700 mg/kg/day for female and 150 mg/kg/day for male. In case of CA, NOAEL of water extract was 1500 mg/kg/day for male and 2000 mg/kg/day for female, while NOAEL of powder was 150 mg/kg/day for both gender. To the best of our knowledge, this is the first sub-chronic toxicity study on the adverse effects, target organs and its dose levels of C. wilfordii (Maxim.) Hemsley and C. auriculatum Royle ex Wight following GLP protocols.

Genotoxicity test of eight natural color additives in the Korean market.

BACKGROUND: Various natural color additives are preferred by many consumers over synthetic color additives because they are perceived to be safer. However, most do not have sufficient toxicity data for safety assurance. Color ingredients in particular have some structures suspected of being toxic. Eight natural color additives, gardenia red, blue, and yellow; lac color; cochineal extract; beet red; Curcuma longa Linne extract (Curcuma extract); and Monascus red, currently permitted for use in Korea, were selected and subjected to genotoxicity tests. Acceptable daily intake values have not been allocated to these color additives (except for cochineal extract) due to the lack of toxicity data. We used genotoxicity testing-the bacterial reverse mutation test (Ames test), in vitro mammalian chromosomal aberration test, and in vivo alkaline comet test-for minimum safety assurance. RESULTS: Gardenia red and blue, cochineal extract, lac color, and beet red did not induce mutagenicity or chromosomal abnormalities. Gardenia yellow was mutagenic in the Ames test, but was not positive in the in vitro chromosomal aberration test or in vivo alkaline comet assay. Curcuma extract and Monascus red induced cytotoxicity in the Ames test at high concentrations in Salmonella typhimurium TA1537 and TA100, without showing mutagenicity. On cytotoxicity testing, Curcuma extract and Monascus red showed cytotoxicity at concentrations higher than 313 µg/ml in Chinese hamster ovary CHO-K1 cells and showed equivocal results in chromosomal aberration assay of the same cells. Curcuma extract and Monascus red produced significant increases in DNA damage at a dose of 2000 mg/kg b.w./day, and induced dose-dependent increases in % DNA in the tail and tail moment on in vivo comet assay. CONCLUSIONS: Six out of eight food colorants did not cause genotoxicity and cytotoxicity. However, Monascus red and Curcuma extract showed definite cytotoxicity and probable genotoxicity.

In silico prediction models for thyroid peroxidase inhibitors and their application to synthetic flavors.

Systematic toxicity tests are often waived for the synthetic flavors as they are added in a very small amount in foods. However, their safety for some endpoints such as endocrine disruption should be concerned as they are likely to be active in low levels. In this case, structure-activity-relationship (SAR) models are good alternatives. In this study, therefore, binary, ternary, and quaternary prediction models were designed using simple or complex machine-learning methods. Overall, hard-voting classifiers outperformed other methods. The test scores for the best binary, ternary, and quaternary models were 0.6635, 0.5083, and 0.5217, respectively. Along with model development, some substructures including primary aromatic amine, (enol)ether, phenol, heterocyclic sulfur, and heterocyclic nitrogen, dominantly occurred in the most highly active compounds. The best predicting models were applied to synthetic flavors, and 22 agents appeared to have a strong inhibitory potential towards TPO activities. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01041-y.

Survey for acrylamide in processed foods from Korean market and individual exposure estimation using a non-parametric probabilistic model.

Acrylamide, a known carcinogen, is formed during preparation of food containing reducing sugar and asparagine. Because acrylamide exposure of the population is primarily through food, the maximum levels of acrylamide in food were set by the European Commission in 2017. Moreover, in the 2016 Korean Total Diet study, acrylamide showed the lowest margin of exposure among 23 food-processing-related chemicals, necessitating risk reduction options. Therefore, the objective of this study was to determine the variation of acrylamide content in different food items and identify the food categories, to provide options for risk management. Acrylamide was analysed using high-performance liquid chromatography coupled with tandem mass spectrometry in more than 1,000 processed food items. To estimate acrylamide exposure, the analytical data obtained herein and the food consumption data of Korean National Health and Nutrition Examination Survey from 2013 to 2017 were used. A non-parametric technique of a probabilistic model was used for exposure estimation. Confectioneries (here this category includes potato and similar savoury snacks) contained a wide range of acrylamide content. Particularly, the highest acrylamide content was detected in a tea made of Jerusalem artichoke. The presence of acrylamide in turmeric along with the Jerusalem artichoke was reported in this study for the first time. The main contributors of dietary acrylamide exposure were confectioneries for youths aged 3-18 years and coffee for adults aged 19-80 years. Therefore, risk management in confectionery and coffee could help reduce acrylamide exposure for Koreans. In addition, the mitigation strategies for food containing high acrylamide content, such as Jerusalem artichoke tea, are needed to reduce acrylamide exposure to loyal consumers.

Carcinogenic risk associated with popular Korean dishes: An approach of combined risk assessments using Oral Slope Factor and BMDL10 values.

Cooking-related carcinogens are formed during the heating or processing of foods. To date, numerous studies analyzing carcinogens present in cooking ingredients or formed through different cooking methods have been conducted. However, combined risk assessment is important for practical reasons. The purpose of this study was to conduct a combined risk assessment of five cooking-related genotoxic carcinogens encompassing 25 chemicals: heterocyclic amines, acrylamide, furan, polycyclic aromatic hydrocarbons, and nitrosamines. Oral Slope Factor (OSF) and benchmark dose lower-bound confidence limit 10% (BMDL10) of the compounds were obtained from public databases, and the values for the compounds that did not have published reference values were approximated using related toxicity values. The high-risk contributing food items and cooking methods for each carcinogen were selected for the study based on the Korean Total Diet Study (TDS) and Korea National Health and Nutrition Examination Survey (KNHANES). Exposure to the carcinogens from selected dishes per serving was estimated based on concentrations determined in TDS and consumption data gathered from 24-h recalls in the 2014 to 2016 KNHANES. The combined cancer risks were obtained by summing the risks of individual compounds in a dish, which were calculated by multiplying the OSF values by the concentrations of carcinogens per serving. The combined risks were used to compare the risk of different dishes, not to calculate the lifetime risk from the individual dishes. The risks of the dishes prepared with potatoes were found to be high, whereas namul (vegetable dish) had the lowest risk. Soup or stew dishes exhibited relatively high risks. Estimated combined risks based on BMDL10 showed similar trends, except for fried potatoes and roasted or fried meat dishes. Combined risks of cooking-related carcinogens may vary based on the major contributors of individual carcinogens. The results of this study could provide an insightful guideline for selecting menus for consumers.

Erratum to "Distribution of Seven N-Nitrosamines in Food" [Toxicol. Res. 31 (2015) 279-298].

[This corrects the article on p. 279 in vol. 31, PMID: 26483887.].

Safety assessment of 16 sweeteners for the Korean population using dietary intake monitoring and poundage method.

A sweetener is a food additive that imparts a sweet taste to food products. Sweeteners have been increasingly used in Korea since the approval of sodium saccharin and d-sorbitol in 1962. Unlike food contaminants, humans are exposed to food additives only through the consumption of processed food products. For exposure assessments of sweeteners, the dietary intakes of food products containing acesulfame-K, aspartame, saccharin-Na, and sucralose were determined, and the resulting calculated estimated daily intake (EDI) values were compared directly with each additive's ADI. The poundage method was used to calculate the daily intake per capita for 12 additional sweeteners, such as lactitol, for which appropriate analytical methods for food products do not exist. The risk, as evaluated by comparing the EDI with the ADI, was determined to be 2.9% for acesulfame-K, 0.8% for aspartame, 3.6% for saccharin-Na, 4.3% for steviol glycosides, and 2.1% for sucralose. No hazardous effect was predicted for the other 11 sweeteners, including lactitol.

Simultaneous determination of sodium saccharin, aspartame, acesulfame-K and sucralose in food consumed in Korea using high-performance liquid chromatography and evaporative light-scattering detection.

Four artificial sweeteners, i.e., sodium saccharin, aspartame, acesulfame-K and sucralose, are permitted for use in Korea, and recent regulatory changes have expanded the number of food categories in which they may be used. Four artificial sweeteners were determined simultaneously in more than 900 food items from 30 food categories that are commercially available in Korean markets, including both domestic and imported products, using high-performance liquid chromatography and evaporative light-scattering detection (ELSD). A new procedure using 75% acetone to remove fat was applied for sample preparation. The levels detected in all samples were below the maximum permitted use levels established in Korea. Despite the increased number of categories, the only one in which sodium saccharin was newly found was takju, an alcoholic beverage. Sodium saccharin was not found in other beverages in the food analysis or in the food label survey, even though its use was reported in a previous study, suggesting that consumer preference outweighs regulatory decisions. When the analytical results were combined with food-consumption data obtained from the Korea National Health and Nutrition Examination Survey 2010-14, the estimated daily intakes of all the sweeteners were considered safe.

Distribution of Seven N-Nitrosamines in Food.

N-nitrosamines, which are classified as carcinogens by IARC and US EPA, can be easily found in various foods. They are reaction products between nitrogen oxide and secondary amines, but can also be generated during fermentation. Ever since the 1960s, when nitrite, used as a preservative in processed meats, was suspected to generate N-nitrosamines, the usage of the food additive has been debated. However, the benefit of nitrite in food supply could not be ignored and the risk-benefit analysis has become a key issue in the use of the additive. For a risk analysis, an accurate estimation of the hazardous material is necessary; therefore, analytical methods for nitrosamines have continuously evolved from the 1950s. Solid supported liquid-liquid extraction and solid phase extractions have replaced the distillation for the clean-up steps, and tandem mass spectrometry is employed for higher selectivity and sensitivity. In the present study, for a better estimation of N-nitrosamine intake, the total diet study samples were prepared for the N-nitrosamines analysis. In order to obtain the most sensitive results, a partial preparation procedure was developed and modified for different food matrices. Among seven N-nitrosamines (N-nitrosodimethylamine, N-nitrosomethylethylamine, N-nitrosodiethylamine, N-nitrosodibutylamine, N-nitrosopiperidine, N-nitrosopyrrolidine, and N-nitrosomorpholine) analyzed in the present study, N-nitrosodiethylamine has shown the highest detection rate in agricultural foods, while N-nitrosodimethylamine has appeared most frequently in livestock and fishery food products. The concentration of N-nitrosodimethylamine was the highest in seasoning.

In vitro metabolic conversion of the organic breakdown products of glucosinolate to goitrogenic thiocyanate anion.

BACKGROUND: Glucosinolates are abundant in Brassicaceae vegetables, and they are degraded into various organic breakdown products (BPs) (R-CN, -NCS and -SCN) by myrosinase when plant tissues are damaged. This study was designed to investigate whether these BPs could be broken further into goitrogenic thiocyanate anions (SCN(-) ) metabolically and/or spontaneously. Ten glucosinolates were chosen for this study based on the various structures of their side chains. SCN(-) and cyanide anions (CN(-) ) liberated from the BPs of these glucosinolates were quantified after incubation with human liver S9 and rhodanese. RESULTS: Upon treatment with metabolic enzymes, CN(-) was produced from all organic thiocyanates, aliphatic and benzyl nitriles, then a substantial amount of produced CN(-) was further metabolized to SCN(-) by rhodanese. All organic thiocyanates and allyl isothiocyanate were metabolized to produce SCN(-), without involving CN(-) production. Spontaneous degradation to SCN(-) in an aqueous environment was observed only in 4-(methylthio)butyl thiocyanate, though the enzymatic reaction rate exceeded the spontaneous one. Among these BPs, the major source of SCN(-) was organic thiocyanates. CONCLUSION: The results show that some organic nitriles, organic thiocyanates and allyl isothiocyanate may be regarded as potential sources of SCN(-) through metabolism when people ingest glucosinolate-containing vegetables.

Supplementation of Seaweeds Extracts Suppresses Azoxymethane-induced Aberrant DNA Methylation in Colon and Liver of ICR Mice.

BACKGROUND: Seamustard and seatangle are commonly consumed seaweeds in Korea and rich sources of non-digestible polysaccharides which possess biological activities. However anti-mutagenic and anti-cancer activities of these seaweeds under physiological condition have not been clarified yet. The objective of this study was to investigate the effect of seaweeds consumption on azoxymethane (AOM) -induced DNA methylation at N(7) and O(6) position of guanine base, an indicator of DNA damage related to cancer initiation. METHODS: THIRTY ICR MICE WERE DIVIDED INTO FIVE GROUPS AND FED ONE OF THE FOLLOWING DIETS FOR TWO WEEKS: control diet, diet containing 10% water-soluble or water-insoluble fraction of seamustard or seatangle. After two weeks of experimental diet AOM was injected at 6 hours before sacrifice and N(7)-methylguanine (N(7)-meG) and O(6)-methylguanine (O(6)-meG) from the colon and liver DNA were quantified using a gas chromatography-mass spectroscopy. RESULTS: Water-soluble fractions of both seamustard and seatangle significantly reduced AOM-induced production of N(7)-meG guanine in colon and liver. Also water-soluble fractions of these seaweeds suppressed the level of methylation at O(6)-guanine of colon and liver directly responsible for tumorigenesis. While water-insoluble fraction of seamustard suppressed the production of N(7)-meG in liver this seaweed fraction decreased O(6)-meG and the ratio of O(6)/N(7)-meG in liver. Water insoluble fraction of seatangle decreased both O(6)- and N(7)-meG in colon and liver. Supplementation of all seaweeds extracts increased fecal weight of animals and the increase of fecal weight by water-insoluble fraction of seaweeds were higher than that by water-soluble fraction. CONCLUSION: Seamustard and seatangle intake may effectively prevent colon and liver carcinogenesis by decreasing DNA damage and the mechanism of inhibiting carcinogenesis by seaweeds in a long term study are warranted.

Determination of goitrogenic metabolites in the serum of male wistar rat fed structurally different glucosinolates.

Glucosinolates (GLSs) are abundant in cruciferous vegetables and reported to have anti thyroidal effects. Four GLSs (sinigrin, progoitrin, glucoerucin, and glucotropaeolin) were administered orally to rats, and the breakdown products of GLSs (GLS-BPs: thiocyanate ions, cyanide ions, organic isothiocyanates, organic nitriles, and organic thiocyanates) were measured in serum. Thiocyanate ions were measured by colorimetric method, and cyanide ions were measured with CI-GC-MS. Organic isothiocyanates and their metabolites were measured with the cyclocondensation assay. Organic nitriles and organic thiocyanates were measured with EI-GC-MS. In all treatment groups except for progoitrin, thiocyanate ions were the highest among the five GLS-BPs. In the progoitrin treated group, a high concentration of organic isothiocyanates (goitrin) was detected. In the glucoerucin treated group, a relatively low amount of goitrogenic substances was observed. The metabolism to thiocyanate ions happened within five hours of the administration, and the distribution of GLSs varied with the side chain. GLSs with side chains that can form stable carbocation seemed to facilitate the degradation reaction and produce a large amount of goitrogenic thiocyanate ions. Because goitrogenic metabolites can be formed without myrosinase, the inactivation of myrosinase during cooking would have no effect on the anti-nutritional effect of GLSs in cruciferous vegetables.

Determination of cyanogenic compounds in edible plants by ion chromatography.

Cyanogenic glycosides are HCN-producing phytotoxins; HCN is a powerful and a rapidly acting poison. It is not difficult to find plants containing these compounds in the food supply and/or in medicinal herb collections. The objective of this study was to investigate the distribution of total cyanide in nine genera (Dolichos, Ginkgo, Hordeum, Linum, Phaseolus, Prunus, Phyllostachys, Phytolacca, and Portulaca) of edible plants and the effect of the processing on cyanide concentration. Total cyanide content was measured by ion chromatography following acid hydrolysis and distillation. Kernels of Prunus genus are used medicinally, but they possess the highest level of total cyanide of up to 2259.81 CN(-)/g dry weight. Trace amounts of cyanogenic compounds were detected in foodstuffs such as mungbeans and bamboo shoots. Currently, except for the WHO guideline for cassava, there is no global standard for the allowed amount of cyanogenic compounds in foodstuffs. However, our data emphasize the need for the guidelines if plants containing cyanogenic glycosidesare to be developed as dietary supplements.

Dietary aloin, aloesin, or aloe-gel exerts anti-inflammatory activity in a rat colitis model.

AIMS: Aloe has been a very popular folk remedy for inflammation-related pathological conditions despite the lack of studies reporting its efficacy in vivo. The present study evaluated the anti-inflammatory effects of aloe components (aloin, aloesin and aloe-gel) known to be biologically active in the rat model of colitis. MAIN METHODS: Male Sprague Dawley rats were fed experimental diets for 2 weeks before and during the induction of colitis. Drinking water containing 3% dextran sulfate sodium (DSS) was provided for 1 week to induce colitis. At the end of the experimental period, clinical and biochemical markers were compared. KEY FINDINGS: Plasma leukotriene B(4) (LTB(4)) and tumor necrosis factor-α (TNF-α) concentrations were significantly decreased in all groups supplemented with aloe components compared to the colitis control group (p<0.05). Animals fed both a 0.1% and 0.5% aloesin supplemented diet showed colonic myeloperoxidase (MPO) activities which were decreased by 32.2% and 40.1%, respectively (p<0.05). Colonic mucosa TNF-α and interleukin-1ß (IL-1ß) mRNA expressions were significantly reduced in all animals fed aloin, aloesin, or aloe-gel (p<0.05). SIGNIFICANCE: Dietary supplementation of aloe components ameliorates intestinal inflammatory responses in a DSS-induced ulcerative colitis rat model. In particular, aloesin was the most potent inhibitor. Further studies are required for a more complete understanding of the specific mechanism of the action of these supplements.

Metabolites of amygdalin under simulated human digestive fluids.

In the present study, degradation of amygdalin in the human digestive fluids and absorption of its metabolites by the human small intestine were evaluated by simulating a gastrointestinal digestion model combined with a human intestinal cell culture. Orally administered amygdalin was degraded into prunasin by digestive enzymes after passing through the salivary and gastrointestinal phases. Prunasin, the major metabolite of amygdalin in the digestive fluids, was incubated in a caco-2 cell culture system. Prunasin was degraded into the mandelonitrile by ß-glucosidase and then hydroxylated across the small intestinal wall, producing hydroxymandelonitrile (149 Da). Results from this study suggest that risk assessment of amygdalin from food consumption can be done in a more accurate way by determining a pathway of amygdalin metabolism in the simulating human upper gastrointestinal tract.

Intestinal absorption of aloin, aloe-emodin, and aloesin; A comparative study using two in vitro absorption models.

Aloe products are one of the top selling health-functional foods in Korea, however the adequate level of intake to achieve desirable effects are not well understood. The objective of this study was to determine the intestinal uptake and metabolism of physiologically active aloe components using in vitro intestinal absorption model. The Caco-2 cell monolayer and the everted gut sac were incubated with 5-50 microM of aloin, aloe-emodin, and aloesin. The basolateral appearance of test compounds and their glucuronosyl or sulfated forms were quantified using HPLC. The % absorption of aloin, aloe-emodin, and aloesin was ranged from 5.51% to 6.60%, 6.60% to 11.32%, and 7.61% to 13.64%, respectively. Up to 18.15%, 18.18%, and 38.86% of aloin, aloe-emodin, and aloesin, respectively, was absorbed as glucuronidated or sulfated form. These results suggest that a significant amount is transformed during absorption. The absorption rate of test compounds except aloesin was similar in two models; more aloesin was absorbed in the everted gut sac than in the Caco-2 monolayer. These results provide information to establish adequate intake level of aloe supplements to maintain effective plasma level.

Evaluation of aloin and aloe-emodin as anti-inflammatory agents in aloe by using murine macrophages.

The aloe ingredients responsible for physiological effects and the concentrations required to exert their biological activities are not fully understood. This study compares the anti-inflammatory effects of aloin and aloe-emodin with other polyphenols. Our results demonstrated that aloe-emodin dose-dependently inhibited inducible nitric oxide synthase (iNOS) mRNA expression and nitric oxide (NO) production at 5-40 microM. In addition, the levels of cyclooxygenase-2 (COX-2) mRNA and prostaglandin E2 (PGE2) production were suppressed by 40 microM aloe-emodin. Aloin also suppressed the production of NO at 5-40 microM, although it did not suppress PGE2 production. The present results indicate that aloin and aloe-emodin possibly suppress the inflammatory responses by blocking iNOS and COX-2 mRNA expression. The anti-inflammatory effect of aloe-emodin was comparable to that of kaempferol and quercetin, indicating aloe-emodin as a possible key constituent responsible for the anti-inflammatory activity of aloe.

Estimated dietary intake of thiocyanate from Brassicaceae family in Korean diet.

Glucosinolate, sulfur-containing organic anions bonded to glucose, is found in plants including the family of Brassicaceae. Glucosinolate is hydrolyzed by myrosinase and produces various by-products that possess biological activities. Among the decomposed products, thiocyanate is known for its adverse effects on thyroid metabolism due to competition with iodine. This is of concern in that Korean dietary habits consist of consumption of large amounts of Brassicaceae vegetables such as cabbage and radishes, which may be correlated with high incidence of thyroid dysfunction. Thus, quantification of thiocyanate in Brassicaceae vegetables was performed by hydrolysis and spectrophotometrical detection. Average daily intake of Brassicaceae vegetables was obtained from the Third Korea National Health and Nutrition Examination Survey (KNHANES III), 2005-Nutrition Survey and from The Vegetable Production Statistics, 2007. Average daily intake of thiocyanate through Brassicaceae vegetables in Korea was estimated to be 16.3 micromol SCN(-)/d/person. When this was compared to published animal studies, average thiocyanate intake per person was lower than doses required to produce adverse effects. However, further studies may be warranted to ensure safety with sufficient margins of safety.

Conversion of Apricot Cyanogenic Glycosides to Thiocyanate by Liver and Colon Enzymes.

Some of the edible plants like apricot kernel, flaxseed, and cassava generate hydrogen cyanide (HCN) when cyanogenic glycosides are hydrolyzed. Rhodanese (thiosulfate: cyanide sulfurtransferases of TSTs; EC: 2.8.1.1) is a sulfide-detoxifying enzymes that converts cyanides into thiocyanate and sulfite. This enzyme exists in a liver and kidneys in abundance. The present study is to evaluate the conversion of apricot cyanogenic glycosides into thiocyanate by human hepatic (HepG2) and colonal (HT-29) cells, and the induction of the enzymes in the rat. The effects of short term exposure of amygdalin to rats have also been investigated. Cytosolic, mitochondrial, and microsomal fractions from HepG2 and HT-29 cells and normal male Spraque-Dawley rats were used. When apricot kernel extract was used as substrate, the rhodanese activity in liver cells was higher than the activity in colon cells, both from established human cell line or animal tissue. The cytosolic fractions showed the highest rhodanese activity in all of the cells, exhibiting two to three times that of microsomal fractions. Moreover, the cell homogenates could metabolize apricot extract to thiocyanate suggesting cellular hydrolysis of cyanogenic glycoside to cyanide ion, followed by a sulfur transfer to thiocyanate. After the consumption of amygdalin for 14 days, growth of rats began to decrease relative to that of the control group though a significant change in thyroid has not been observed. The resulting data support the conversion to thiocyanate, which relate to the thyroid dysfunction caused by the chronic dietary intake of cyanide. Because Korean eats a lot of Brassicaceae vegetables such as Chinese cabbage and radish, the results of this study might indicate the involvement of rhodanese in prolonged exposure of cyanogenic glycosides.

Plasma, tissue and urinary levels of aloin in rats after the administration of pure aloin.

Aloin is a physiologically active anthraquinone present in aloe. There are two isomers of aloin, aloin A and aloin B, occurring as a mixture of diastereomers. The objective of this study was to determine the bioavailability and tissue distribution of aloin. Rats were gavaged with 11.8g/kg aloin, and the levels of aloin and its conjugates were measured in plasma, tissues, and urine. Plasma aloin level showed a peak at 1hr after the administration and the concentration was 59.07+/-10.5 ng/ml. The 24 h cumulated urinary aloin was 0.03% of the initial dose. These results suggest that aloin is absorbed and reaches a peak plasma level within 1-1.5 h after the administration and a significant portion is possibly metabolized or is excreted in feces. These results can apply to the determination of the adequate intake level of aloe and aloe products to achieve the desired biological effect, and to interprete in vitro study results.