Title
Lycopene synergistically inhibits LDL oxidation in
combination with vitamin E, glabridin, rosmarinic acid, carnosic acid, or
garlic.
Source
Antioxidants & Redox
Signaling. 2(3):491-506, 2000 Fall.
Abstract
Several lines of evidence suggest that oxidatively modified low-density
lipoprotein (LDL) is atherogenic, and that atherosclerosis can be attenuated
by natural antioxidants, which inhibit LDL oxidation. This
study was conducted to determine the effect of tomato
lycopene alone, or in combination with other natural
antioxidants, on LDL oxidation. LDL (100 microg of
protein/ml) was incubated with increasing concentrations of
lycopene or of tomato oleoresin (lipid extract of tomatoes
containing 6% lycopene, 0.1% beta-carotene, 1% vitamin E,
and polyphenols), after which it was oxidized by the addition of 5
micromol/liter of CuSO4. Tomato oleoresin exhibited superior capacity to
inhibit LDL oxidation in comparison to pure lycopene, by up
to five-fold [97% vs. 22% inhibition of thiobarbituric acid reactive
substances (TBARS) formation, and 93% vs. 27% inhibition of lipid peroxides
formation, respectively]. Because tomato oleoresin also contains, in addition
to lycopene, vitamin E, flavonoids, and phenolics, a
possible cooperative interaction between lycopene and such
natural antioxidants was studied. A combination of
lycopene (5 micromol/liter) with vitamin E
(alpha-tocopherol) in the concentration range of 1-10 micromol/liter resulted
in an inhibition of copper ion-induced LDL oxidation that was significantly
greater than the expected additive individual inhibitions. The synergistic
antioxidative effect of lycopene with vitamin E was not
shared by gamma-to-cotrienol. The polyphenols glabridin (derived from
licorice), rosmarinic acid or carnosic acid (derived from rosemary), as well
as garlic (which contains a mixture of natural antioxidants)
inhibited LDL oxidation in a dose-dependent manner. When
lycopene (5 micromol/liter) was added to LDL in combination
with glabridin, rosmarinic acid, carnosic acid, or garlic, synergistic
antioxidative effects were obtained against LDL oxidation induced either by
copper ions or by the radical generator AAPH. Similar interactive effects
seen with lycopene were also observed with beta-carotene,
but, however, to a lesser extent of synergism. Because natural
antioxidants exist in nature in combination, the in vivo
relevance of lycopene in combination with other natural
antioxidants was studied. Four healthy subjects were
administered a fatty meal containing 30 mg of lycopene in
the form of tomato oleoresin. The lycopene concentration in
postprandial plasma was elevated by 70% in comparison to plasma obtained
before meal consumption. Postprandial LDL isolated 5 hr after meal
consumption exhibited a significant (p < 0.01) reduced susceptibility to
oxidation by 21%. We conclude that lycopene acts
synergistically, as an effective antioxidant against LDL oxidation, with
several natural antioxidants such as vitamin E, the
flavonoid glabridin, the phenolics rosmarinic acid and carnosic acid, and
garlic. These observations suggest a superior antiatherogenic characteristic
to a combination of different natural antioxidants over that
of an individual one.
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