Novel Antioxidative Metabolites in Rat Liver with Ingested Sesamin

Abstract

Sesamin, a major lignan in sesame oil, is known to have many biological activities, especially protective effects against oxidative damage in the liver. As sesamin itself has no antioxidative properties in vitro, to elucidate the mechanism of its antioxidative effects, the reaction products of sesamin in rat liver homogenate were analyzed. The methylenedioxyphenyl moiety in the structure of sesamin was shown to be changed into a dihydrophenyl (catechol) moiety. The enzymatic reaction products in vitro were identified as (1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3,3,0]octane and (1R,2S,5R,6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane, which showed strong radical scavenging activities; the latter was a novel compound. The same metabolites were found as glucuronic acid and/or sulfic acid conjugates in substantial amounts in rat bile after oral administration of sesamin. It is suggested that sesamin is a prodrug and the metabolites containing the catechol moieties in their structures are responsible for the protective effects of sesamin against oxidative damage in the liver.

Formation of two methylenedioxy bridges by a Sesamum CYP81Q protein yielding a furofuran lignan, (+)-sesamin

“…It has a growth-retarding effect on some plants, as well as a synergistic effect with pyretherum insecticides (5,6). (ϩ)-Sesamin has been shown to have a wide range of biological effects: protection against ethanol-and carbon tetrachloride-induced liver damage (7,8), improvement of fatty acid metabolism (9)(10)(11), antiinflammatory effects (12), increased vitamin E activities (13,14), inhibition of vascular superoxide production (15,16), and induction of nitric oxide (17). Therefore, it is an extremely interesting natural compound from the viewpoint of health care (18).…”

Optimization Protocol for the Microwave-Assisted Extraction of Antioxidant Components from Pinus elliottii Needles Using Response Surface Methodology

“…Superoxide anion radical (O2 − ) scavenging activity was analyzed by electron spin resonance (ESR) spectroscopy, which used the 5,5-dimethyl-1-pyrroline N-oxide (DMPO) spin adduct generated by the hypoxanthine and xanthine oxidase reaction (Nakai et al 2003). ESR spectra were recorded with a JEOL JES-FR30 spectrometer (Tokyo, Japan), which used an aqueous quartz flat cell (JEOL LC-12 ESR cuvette; internal size 60 × 10 × 0.31 mm; effective volume of 160 μL).…”

“…Hydroxy radical (·OH) scavenging activity was analyzed in the same way as superoxide anion radical scavenging activity, which used the DMPO spin adduct generated by the Fenton reaction (Nakai et al 2003). The absolute concentration of DMPO-·OH was determined by the double integration of the ESR spectrum.…”

Evaluation of Antioxidative Effects of Sesamin on the In vivo Hepatic Reducing Abilities by a Radiofrequency ESR Method

“…1). 1 The multiple biological functions of sesamin and episesamin that have been previously reported include the inhibition of ∆5-desaturase, 2 antioxidant activities, [3][4][5][6][7][8] and anti-inflammatory and antihypertensive effects. [8][9][10] Several studies have described the suppressive effects of sesamin on lipid peroxidation in vivo.…”

“…3,4 The scavenging effects of sesamin and episesamin (sesamin:episesamin = 51.1:48.2, w/w) on superoxide anion radical (O2 • -) and hydroxyl radical (·OH) were very weak in vitro. 6,11 A previous study that used an electron spin resonance (ESR) spin trapping assay found the O2 • -scavenging activity of a mixture of sesamin and episesamin (final concentration, 50 μM) was 3.0%, while the ·OH scavenging activity of the mixture (final concentration, 250 μM) was 2.3%. 11 On the other hand, Nakai et al reported that sesamin was metabolized in the liver to (1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo [3,3,0]octane (SC-1) and (1R,2S,5R,6S)-2,6-bis-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo [3,3,0]octane (SC-2), which can act as a strong antioxidant.…”