Serotonin Derivatives, Major Safflower (Carthamus tinctorius L.) Seed Antioxidants, Inhibit Low-Density Lipoprotein (LDL) Oxidation and Atherosclerosis in Apolipoprotein E-Deficient Mice
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The effects of defatted safflower seed extract and its phenolic constituents, serotonin derivatives, onatherosclerosis 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 orcopper ions. Two serotonin derivatives [N-(p-coumaroyl)serotonin, CS; N-feruloylserotonin, FS] andtheir glucosides were identified as the major phenolic constituents of the extract. The study withchemically synthesized materials revealed that a majority of the antioxidative activity of SSE wasattributable to the aglycones of these two serotonin derivatives. Orally administered CS and FSsuppressed CuSO4-induced plasma oxidation ex vivo. Long-term (15 week) dietary supplementationof SSE (1.0 wt %/wt) and synthetic serotonin derivatives (0.2-0.4%) significantly reduced theatherosclerotic 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 titersdecreased concomitantly with the reduction of lesion formation. Serotonin derivatives were detectedas 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 andattenuate atherosclerotic lesion development possibly because of the inhibition of oxidized LDLformation through their strong antioxidative activity.Keywords: Safflower; serotonin derivatives; antioxidants; LDL oxidation; apoE-deficient mice

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