Pharmacokinetics of Cycloalliin, an Organosulfur Compound Found in Garlic and Onion, in Rats
详细信息 查看全文
- 作者：Makoto Ichikawa ; Ikuko Mizuno ; Jiro Yoshida ; Nagatoshi Ide ; Mitsuyasu Ushijima ; Yukihiro Kodera ; Minoru Hayama ; Kazuhisa Ono
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2006
- 出版时间：December 27, 2006
- 年：2006
- 卷：54
- 期：26
- 页码：9811 - 9819
- 全文大小：123K
- 年卷期：v.54,no.26(December 27, 2006)
- ISSN：1520-5118
文摘
Cycloalliin, an organosulfur compound found in garlic and onion, has been reported to exert severalbiological activities and also to remain stable during storage and processing. In this study, weinvestigated the pharmacokinetics of cycloalliin in rats after intravenous or oral administration.Cycloalliin and its metabolite, (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid, in plasma, urine, feces,and organs was determined by a validated liquid chromatography-mass spectrometry method. Whenadministered intravenously at 50 mg/kg, cycloalliin was rapidly eliminated from blood and excretedinto urine, and its total recovery in urine was 97.8% ± 1.3% in 48 h. After oral administration, cycloalliinappeared rapidly in plasma, with a tmax of 0.47 ± 0.03 h at 25 mg/kg and 0.67 ± 0.14 h at 50 mg/kg.Orally administered cycloalliin was distributed in heart, lung, liver, spleen, and especially kidney.The Cmax and AUC0-inf values of cycloalliin at 50 mg/kg were approximately 5 times those at 25mg/kg. When administered orally at 50 mg/kg, cycloalliin was excreted into urine (17.6% ± 4.2%)but not feces. However, the total fecal excretion of (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acidwas 67.3% ± 5.9% (value corrected for cycloalliin equivalents). In addition, no (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid was detected in plasma (<0.1 
g/mL), and negligible amounts (1.0%± 0.3%) were excreted into urine. In in vitro experiments, cycloalliin was reduced to (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid during anaerobic incubation with cecal contents of rats. These dataindicated that the low bioavailability (3.73% and 9.65% at 25 and 50 mg/kg, respectively) of cycloalliinwas due mainly to reduction to (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid by the intestinal floraand also poor absorption in the upper gastrointestinal tract. These findings are helpful for understandingthe biological effects of cycloalliin.
g/mL), and negligible amounts (1.0%± 0.3%) were excreted into urine. In in vitro experiments, cycloalliin was reduced to (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid during anaerobic incubation with cecal contents of rats. These dataindicated that the low bioavailability (3.73% and 9.65% at 25 and 50 mg/kg, respectively) of cycloalliinwas due mainly to reduction to (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid by the intestinal floraand also poor absorption in the upper gastrointestinal tract. These findings are helpful for understandingthe biological effects of cycloalliin.