Novel antioxidative metabolites in rat liver with ingested sesamin.
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.
Nakai
Masaaki
M
Institute for Health Care Science, Suntory Ltd., 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan. Masaaki_Nakai@suntory.co.jp
Harada
Masami
M
Nakahara
Koichi
K
Akimoto
Kengo
K
Shibata
Hiroshi
H
Miki
Wataru
W
Kiso
Yoshinobu
Y
D000818:Animals; D000975:Antioxidants / Q000032:analysis* / Q000378:metabolism* / Q000494:pharmacology; D001646:Bile / Q000737:chemistry; D001713:Biphenyl Compounds; D002851:Chromatography, High Pressure Liquid; D004149:Dioxoles / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000737:chemistry; D017665:Hydroxyl Radical / Q000737:chemistry; D017705:Lignans / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010851:Picrates / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization
D000975:Antioxidants; D001713:Biphenyl Compounds; D004149:Dioxoles; D016166:Free Radical Scavengers; D017705:Lignans; D010851:Picrates; D017665:Hydroxyl Radical; C004931:1,1-diphenyl-2-picrylhydrazyl; C054125:sesamin