title: Serotonin derivatives, major safflower (Carthamus tinctorius L.) seed antioxidants, inhibit low-density lipoprotein (LDL) oxidation and atherosclerosis in apolipoprotein E-deficient mice.
abstract: The effects of defatted safflower seed extract and its phenolic constituents, serotonin derivatives, on atherosclerosis were studied. Ethanol-ethyl acetate extract of safflower seeds (SSE) inhibited low-density lipoprotein (LDL) oxidation induced in vitro by an azo-containing free-radical initiator V70 or copper ions. Two serotonin derivatives [N-(p-coumaroyl)serotonin, CS; N-feruloylserotonin, FS] and their glucosides were identified as the major phenolic constituents of the extract. The study with chemically synthesized materials revealed that a majority of the antioxidative activity of SSE was attributable to the aglycones of these two serotonin derivatives. Orally administered CS and FS suppressed CuSO(4)-induced plasma oxidation ex vivo. Long-term (15 week) dietary supplementation of SSE (1.0 wt %/wt) and synthetic serotonin derivatives (0.2-0.4%) significantly reduced the atherosclerotic lesion area in the aortic sinus of apolipoprotein E-deficient mice (29.2-79.7% reduction). The plasma level of both lipid peroxides and anti-oxidized LDL autoantibody titers decreased concomitantly with the reduction of lesion formation. Serotonin derivatives were detected as both intact and conjugated metabolites in the plasma of C57BL/6J mice fed on 1.0% SSE diet. These findings demonstrate that serotonin derivatives of SSE are absorbed into circulation and attenuate atherosclerotic lesion development possibly because of the inhibition of oxidized LDL formation through their strong antioxidative activity.
authors.affiliation: Research Institute for Health Fundamentals, Ajinomoto Co., Inc., Kawasaki 210-8681, Japan. naoto_koyama@ajinomoto.com
authors.forename: Naoto
authors.initials: N
authors.lastname: Koyama
authors.forename: Kanna
authors.initials: K
authors.lastname: Kuribayashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Seki
authors.forename: Katsunori
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Furuhata
authors.forename: Katsuya
authors.initials: K
authors.lastname: Suzuki
authors.forename: Harumi
authors.initials: H
authors.lastname: Arisaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Amino
authors.forename: Koichi
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000517:prevention & control*; D031187:Carthamus tinctorius / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000494:pharmacology; D012639:Seeds / Q000737:chemistry; D012701:Serotonin / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D010936:Plant Extracts; C512561:N-feruloylserotonin; D012701:Serotonin; C114774:N-(p-coumaroyl)serotonin