S 36 Research Article Elimination and metabolism of sesamol, a bioactive compound in sesame oil, in rats Kuo-Ching Jan 1 , Chi-Tang Ho 1, 2 and Lucy Sun Hwang 1 1 Graduate Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan 2 Department of Food Science, Rutgers University, New Brunswick, NJ, USA Sesamol, generally regarded as a main antioxidative component in sesame oil, is generated from ses- amolin upon roasting of sesame seed or during bleaching process of sesame oil. This investigation studied the bioavailability and excretion of sesamol in Sprague-Dawley rats. After oral administration of sesamol (p.o. 100 mg/kg) to SD rats, the changes in concentration of sesamol were determined in various excreta within 24 h period. Our results showed that sesamol conjugated metabolites were rap- idly eliminated from urine and feces in 0 – 4 h. The majority of intact sesamol glucuronide was excreted in the urine. It is suggested that sesamol conjugated metabolites are primarily eliminated from the plasma via the kidney by active tubular secretion. LC-MS/MS analyses of rat excreta showed that sesamol can be converted to 2-methoxybenzene-1,4-diol and benzene-1,2,4-triol in vivo by rat. Keywords: Benzene-1,2,4-triol / Elimination / 2-Methoxybenzene-1,4-diol / Sesamol / Sesamol glucuronide / Received: June 2, 2008; revised: June 25, 2008; accepted: July 2, 2008 1 Introduction Sesame, an important oilseed derived from Sesamum indi- cum, is one of the oldest oilseeds known to humans and is considered to have nutritional value as well as medicinal effects. The seed contains two lignans, sesamin, and sesa- molin. Upon roasting sesame seeds, sesamolin is converted to sesamol [1, 2]. Sesamol has been found to have antioxi- dative effects [3] and to induce growth arrest and apoptosis in cancer cells [4]. Recently, the antiphotooxidative activity of sesamol for oil has been reported to be due to the scav- enging of singlet oxygen [5]. Sesamol has a phenolic and a benzodioxole group in its molecular structure. The phenolic groups of molecules are generally responsible for the antioxidant activity of many natural products [6– 9]. On the other hand, benzodioxole derivatives are widely distributed in nature and have been shown to possess antitumor, antioxidant and many other biological activities [10– 13]. These activities have been attributed to the effect on various enzymes as well as scav- enging of reactive oxygen species. Sesamol could also attenuate the production of nitric oxide and hydrogen per- oxide and reduce monoamine oxidase activity in glial astro- cyte cells [14]. Since a distinct relationship exists between monoamine oxidase activity and the development of neuro- degenerative diseases associated with aging such as Alz- heimer's disease and stroke, sesamol might play a role in the prevention of these types of diseases. In addition, fibri- nolysis is considered as a risk factor for severe cardiovascu- lar diseases such as myocardial infarction and stroke [15– 17]. Sesamol may enhance overall vascular fibrinolytic capacity through regulating gene expression of plasmino- gen activator [18]. However, there are no comprehensive and in-depth investigations on the elimination and metabo- lism of sesamol in vivo. The aim of this study was to eluci- date the metabolic fate of sesamol after its oral administra- tion in rats. 2 Materials and methods 2.1 Chemicals Sesamol, D-saccharic acid-1,4-lactone, hesperetin, 2-meth- oxybenzene-1,4-diol, benzene-1,2,4-triol, and sulfatase (Helix pomatia, S-9626) were obtained from Sigma– Aldrich (St. Louis, MO, USA). All other chemicals used were of analytical grade. Liquid chromatographic grade solvents and reagents were obtained from Mallinckrodt Correspondence: Professor Lucy Sun Hwang, Graduate Institute of Food Science and Technology, National Taiwan University, Taipei, Tai- wan E-mail: lshwang@ntu.edu.tw Fax: +886-2-23620849 Abbreviations: SGF, simulated gastric; SIF, intestinal fluid; SRM, se- lected reaction monitoring i 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.mnf-journal.com DOI 10.1002/mnfr.200800214 Mol. Nutr. Food Res. 2009, 53, S36 – S43