n-feruloylserotonin and Atherosclerosis

Pulse wave velocity (PWV) has been used clinically as a direct measure of arterial stiffness. We investigated the inhibitory effects of defatted safflower seed extract (SSE) and serotonin derivatives (N-(p-coumaroyl)serotonin, N-feruloylserotonin; CS+FS), which are the active components in SSE, on hypercholesterolemia and atherosclerosis, using PWV in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. SSE and CS+FS were supplemented with a commercial diet containing 0.5% cholesterol for 8 weeks in male KHC rabbits, aged 2 months. Pulse waves were recorded at different aortic positions using two catheters with micromanometers under pentobarbital anesthesia. The atherosclerotic lesioned area in the aorta was significantly reduced in the SSE and CS+FS groups, without significant changes in serum cholesterol and triglyceride levels among the three groups after supplementation. Local PWV (LPWV) in the middle thoracic and distal abdominal aortas was significantly smaller in the SSE and CS+FS groups than in the control group. PWV in the entire aorta was also significantly lower in the SSE and CS+FS groups, compared with that in the control group. Pressure-strain elastic modulus, an index of wall distensibility, was significantly lower in the middle thoracic and middle abdominal aortas in the SSE and CS+FS groups than in the control group. Wall thickness was also significantly smaller in the middle thoracic aorta in the SSE and CS+FS groups compared with that in the control group. Serotonin derivatives inhibited the progress of atherosclerosis and ameliorated wall distensibility, which contributed, in part, to the lowering of LPWV. Serotonin derivatives may be beneficial in improving vascular distensibility and in reducing cardiovascular risk.

Topics: Animals; Aorta; Atherosclerosis; Body Weight; Carthamus tinctorius; Cholesterol, Dietary; Dietary Supplements; Eating; Hypercholesterolemia; Male; Myocardium; Plant Oils; Pulse; Rabbits; Serotonin; Tensile Strength; Thiobarbituric Acid Reactive Substances

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.

Topics: Animals; Antioxidants; Apolipoproteins E; Atherosclerosis; Carthamus tinctorius; Chromatography, High Pressure Liquid; Lipid Peroxidation; Lipoproteins, LDL; Male; Mice; Mice, Inbred C57BL; Plant Extracts; Seeds; Serotonin