Lycopene Synergistically Inhibits LDL Oxidation in Combination with Vitamin E, Glabridin, Rosmarinic Acid, Carnosic Acid, or Garlic

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.

Tomatoes versus lycopene in oxidative stress and carcinogenesis: conclusions from clinical trials

“…This study also confirms the synergy among tomato antioxidants, including lycopene, in reducing lipid peroxidation, as reported by in vitro data (Fuhrman et al, 2000). As patients with type II diabetes are at an increased risk of developing coronary heart disease, and oxidized LDLs have been shown to contribute to this risk of arterial disease (Libby, 2006), tomato product supplementation maybe of potential benefit in these patients.…”

“…Purified lycopene in association with a-tocopherol or tomato lipophilic extracts has been shown to enhance acyl-PAF biosynthesis in endothelial cells during oxidative stress (Balestrieri et al, 2004). Fuhrman et al (2000) further reported comparative data in which tomato oleoresin exhibited superior capacity to inhibit in vitro LDL oxidation in comparison with pure lycopene, by up to fivefold. A combination of purified lycopene (5 mmol/l) with a-tocopherol in the concentration range of 1-10 mmol/l resulted in a significant greater inhibition of in vitro LDL oxidation, than the expected additive individual inhibitions.…”

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

“…The transfection of Nm23 c DNA into various cancer cell lines results in the suppression of metastatic potential such as in motility, invasion or colonization indicating that Nm23 as a potential metastasis suppressor gene that could function on the invasion and migration steps of the metastatic pathway (Khan et al, 2001;Liu et al, 2002). There are about eight human Nm23 genes were characterized, of which the H1 gene is most closely correlated with the metastatic phenotype in human breast carcinoma, colorectal carcinoma, ovarian carcinoma and hepatocarcinoma (Fuhrman et al, 2000;Sies and Stahl, 2003). In human tissues, the two most abundantly expressed Nm23 genes are Nm23-H1 and Nm23-H2 or NME1 and NME2, respectively.…”

Does rosmarinic acid underestimate as an experimental cardiovascular drug?

“…The presence of rosmarinic acid (RA) in medicinal plants, herbs and spices, has been generated healthy and beneficial effects. Among these were several RA biological activities, including antioxidant, astringent, anti-inflammatory, antimicrobial, antiangiogenic, antiviral, antirheumatic, antiallergic, antidepressant, antidiabetic, and antitumor [2][3][4][5][6][7][8][9][10][11][12][13] . However, reports on its activity in the cardiovascular system are scarce.…”