Namino Tomimori

Scope: Sesamin is a major lignan in sesame seeds and has various physiological effects. Although metabolism of sesamin by cytochrome P450 or intestinal microflora has been reported, little is known concerning the mass balance, pharmacokinetics, and tissue distribution of sesamin.Methods and results: Absorption, distribution, metabolism, and excretion of [¹⁴C]sesamin were investigated after a single oral dose of 5 mg/kg in rats. Sesamin was absorbed with peak plasma radioactivity at 1.0 h and declined with a terminal half‐life 4.7 h. The cumulative excretion of radioactivity was 37.5 ± 3.1% in urine and 58.7 ± 4.8% in feces. In bile duct‐cannulated rats, the cumulative excretion of radioactivity was 66.3 ± 8.4% in bile and 27.8 ± 10.2% in urine. Tissue distribution was investigated using quantitative whole‐body autoradiography. Radioactivity was widely distributed over the whole body and was highly detected in the liver and kidney. The metabolites profile was examined using radiochromatography. Sesamin was mainly distributed in the form of conjugate metabolites.Conclusions: Sesamin was absorbed efficiently and distributed over the whole body. In particular, sesamin was highly distributed in the form of the metabolites in the liver and kidney. The results of this study are useful in elucidating the action mechanism of sesamin.

A single‐blind, placebo‐controlled, parallel‐group and multiple oral dose study was conducted in 48 healthy subjects to investigate the pharmacokinetics and safety of multiple oral doses of sesame lignans (sesamin and episesamin). Subjects were randomly divided into two groups. Each subject was administered 50 mg of sesame lignans (sesamin/episesamin = 1/1) or placebo once daily for 28 days. The pharmacokinetics of the sesame lignans were investigated using 10 of the 24 subjects in the sesame lignans group. No serious adverse events were observed in this study. Sesamin was absorbed with a peak plasma concentration at 5.0 h. The plasma concentration of the main metabolite, SC‐1, reached a peak at 5.0 h and decreased rapidly with a terminal half‐life of 2.4 h. Episesamin was also absorbed with a peak plasma concentration at 5.0 h and decreased with a terminal half‐life of 7.1 h. The plasma concentration of the main metabolite, EC‐1, reached a peak at 5.0 h and decreased rapidly with a terminal half‐life of 3.4 h. The plasma concentrations of sesamin and episesamin reached a steady state by day 7. Sesame lignans were confirmed to be safe and tolerable in healthy subjects. The results of the pharmacokinetic study demonstrate that no accumulation was observed following multiple 50 mg doses of sesame lignans. Copyright © 2013 John Wiley & Sons, Ltd.

Episesamin is an isomer of sesamin, resulting from the refining process of non-roasted sesame seed oil. Episesamin has two methylendioxyphenyl groups on exo and endo faces of the bicyclic skeleton. The side methylendioxyphenyl group was metabolized by cytochrome-P450. Seven metabolites of episesamin were found in rat bile after treatment with glucuronidase/arylsulfatase and were identified using NMR and MS. The seven metabolites were (7α,7′β,8α,8′α)-3,4-dihydroxy-3′,4′-methylenedioxy-7,9′:7′,9-diepoxylignane (EC-1-1), (7α,7′β,8α,8′α)-3,4-methylenedioxy-3′,4′-dihydroxy-7,9′:7′,9-diepoxylignane (EC-1-2) and (7α,7′β,8α,8′α)-3,4:3′,4′-bis(dihydroxy)-7,9′:7′,9-diepoxylignane (EC-2), (7α,7′β,8α,8′α)-3-methoxy-4-hydroxy-3′,4′-methylenedioxy-7,9′:7′,9-diepoxylignane (EC-1m-1), (7α,7′β,8α,8′α)-3,4-methylenedioxy-3′-methoxy-4′-hydroxy-7,9′:7′,9-diepoxylignane (EC-1m-2), (7α,7′β,8α,8′α)-3-methoxy-4-hydroxy-3′,4′-dihydroxy-7,9′:7′,9-diepoxylignane (EC-2m-1) and (7α,7′β,8α,8′α)-3,4-dihydroxy-3′-methoxy-4′-hydroxy-7,9′:7′,9-diepoxylignane (EC-2m-2). EC-1-1, EC-1-2 and EC-2 were also identified as metabolites of episesamin in human liver microsomes. These results suggested that similar metabolic pathways of episesamin could be proposed in rats and humans.