**3. Chemical composition of lycopene**

Lycopene is a lipophelic, 40-carbon atom highly unsaturated, straight chain hydrocarbon containing 11 conjugated and 2 non-conjugated double bonds. The all-trans isomer of lycopene is the most predominant isomer in fresh tomatoes and is the most thermodynamically stable from (figure 1). The many conjugated double bonds of lycopene make it a potentially powerful antioxidant, a characteristic believed to be responsible for its beneficial effects. The antioxidant activity of lycopene is high light by its singlet oxygen-quenching property and its ability to trap peroxy1 radicals. This singlet quenching ability of lycopene is twice as high as that of βcarotene and 10 times higher than that of α-tocopherol and butylated hydroxyl toluene.

**Figure 1.** All-*trans* Lycopene.

490 Lipoproteins – Role in Health and Diseases

other lycopene containing fruits and vegetables.

**3. Chemical composition of lycopene** 

Source Lycopene content (mg/100g wet basis)

**Table 1.** shows the lycopene content of tomatoes, some commonly consumed tomato products and

and may help lower the risk of chronic diseases including cancer and heart disease.

Lycopene is a lipophelic, 40-carbon atom highly unsaturated, straight chain hydrocarbon containing 11 conjugated and 2 non-conjugated double bonds. The all-trans isomer of lycopene is the most predominant isomer in fresh tomatoes and is the most thermodynamically stable from (figure 1). The many conjugated double bonds of lycopene make it a potentially powerful antioxidant, a characteristic believed to be responsible for its beneficial effects. The antioxidant

Lycopene is also widely distributed in the human body. It is one of the major carotenoids found in the human serum (between 21 and 43% of total carotenoids) with plasma levels ranging from 0.22 to 1.06 nmol/ml (Cohen, 2002). It is also found in various tissues throughout the body such as the liver, kidney, adrenal glands, tests, ovaries and the prostate gland (Basu & Imrhan, 2006). Unlike other carotenoids like α-and β-carotene, lycopene lacks the β.:onone rang structure common to other carotenooids (Agarwal & Rao, 2000). Although it lacks provitamine an activity, lycopene is known to be a potent antioxidant (Livny *et al.,* 2002). Reactive oxygen (ROS) species have been implicated in playing a major role in the causation and progression of several chronic diseases. These ROS are highly reactive oxidant molecules that are generated endogenously through regular metabolic activity. They react with cellular components, causing oxidative damage to such critical cellular biomolecules as lipids, proteins and DNA. Antioxidants are protective agents that inactive ROS and therefore, significantly delay or prevent oxidative damage associated with chronic disease risk. Lycopene is one of the most potent antioxidants among the dietary carotenoids

Tomatoes fresh 0.72 – 20 Tomato juice 5.00 – 11.60 Tomato sauce 6.20 Tomato paste 5.40 – 15.00 Tomato soup 7.99 Ketchup 9.90 – 13.44 Pizza sauce 12.71 Watermelon 2.30 – 7.20 Pink guava 5.23 – 5.50 Pink grapefruit 0.35 – 3.36 Papaya 0.11 – 5.30 Carrot 0.65 – 0.78 Pumpkin 0.38 – 0.46 Sweet potato 0.02 – 0.11 Apricot 0.01- 0..05

As a result of the 11 conjugated carbon-carbon double bonds in its backbone, lycopene can theoretically assume 211 or 2048 geometrical configurations (Omani & Aluko, 2005).

However, it is now known that the biosynthesis in plants leads to the all-*trans*-form, and this is independent of its thermodynamic stability. In human plasma, lycopene is an isomeric mixture, containing at least 60% of the total lycopene as cis- isomers ( Kim *et al.,* 2012).

All-*trans*, 5-*cis*, 9-*cis*, 13-*cis*, and 15-*cis* are the most commonly identified isomeric forms of lycopene with the stability sequence being 5-*cis*>all-*trans*>9-*cis*>13-*cis*>15- *cis*>7-*cis*>11-*cis*, (Agarwal & Rao, 2000) so that the 5-*cis*-form is thermodynamically more stable than the all*trans*-isomer. Whereas a large number of geometrical isomers are theoretically possible for all-*trans* lycopene, according to only certain ethylenic groups of a lycopene molecule can participate in *cis-trans* isomerization because of steric hindrance. In fact, only about 72 lycopene *cis* isomers are structurally favorable. Figure 2 illustrates the structural distinctions of the predominant lycopene geometrical isomers.

**Figure 2.** Geometrical isomers of lycopene

#### **4. Mechanisms action of lycopene**

A cellular and molecular study have shown lycopene to be one of the most potent antioxidants and has been suggested to prevent atherogenesis by protecting critical bimolecules such as DNA, proteins, lipids and low density lipoproteins (Pool-zobel *et al.,* 1997). Lycopene, because of its high number of conjugated double bonds, exhibits higher singlet oxygen quenching ability compared to β-carotene or α-tocopherol (Di-Mascio *et al.,* 1989). Cis lycopene has been shown to predominate in both benign and malignant prostate tissues, suggesting a possible beneficial effect of high cis-isomer concentrations, and also the involvement of tissue isomerases in vivo isomerization from all trans to cis form (Clinton *et al.,* 1996). Where as Levin *et al.,* (1997) have shown that 9- cis- β-carotene is a better antioxidant than its all-trans counterpart, no such mechanistic data have been reported in case of individual lycopene isomers. Handley *et al.,* (2003) reported a significant increase in 5-cis lycopene concentrations following a 1- week lycopene-restricted diet, and a subsequent reduction in 5-cis, and a concomitant increase in cis-β, cis-D and cis-E lycopene isomers during the 15-day dietary intervention with tomato products in healthy individuals. Although this study reported a decrease in LDL oxidizability due to the intervention with tomato lycopene, the individual antioxidant role of lycopene isomers and their inter conversions remain unclear. At a physiological concentration of 0.3 μmol/1, lycopene has been shown to inhibit growth of non-neoplastic human prostate epithelial cells in vitro, through cell cycle arrest which may be of significant implications in preventing benign prostate hyperplasia, a risk factor for prostate cancer (Obermuller-Jevic *et al.,* 2003). Lycopene has also been shown to significantly reduce LNCaP human prostate cancer cell survival in a dose-dependent manner, and this anti-neoplastic action may be explained by increased DNA damage at high lycopene concentrations (> 5μm), whereas lower levels of lycopene reduced malondialdehyde formation, with no effects on DNA (Hwang & Bowen, 2005). Physiologically attainable concentrations of lycopene have been shown to induce mitochondrial apoptosis in LNCaP human prostate cancer cells, although no effects were observed on cellular proliferation or necrosis (Hantz *et al.,* 2005). Lycopene has also been shown to interfere in lipid metabolism, lipid oxidation and corresponding development of atherosclerosis. Lycopene treatment has been shown to cause a 37% suppression of cellular cholesterol synthesis in J-774A.1 macrophage cell line, and augment the activity of macrophage LDL receptors (Fuhrman *et al.,* 1997). Oxidized LDLs are highly atherogenic as they stimulate cholesterol accumulation and foam cell formation, initiating the fatty streaks of atherosclerosis (Libby, 2006). LDL susceptibility to oxidative modifications is decrease by an acyl analog of platelet-activating (PAF), acyl-PAF, which experts its beneficial role during the initiation and progression of atherosclerosis. Purified lycopene in association with αtocopherol or tomato lipophillic 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 (5μmol/I) with α-toopherol in the concentration range of 1-10μmol/I resulted in a significant greater inhibition of in vitro LDL oxidation, than the expected additive individual inhibitions. In this study, purified lycopene was also shown to act synergistically with other natural antioxidants like the flavonoid glabridin, the phenolics rosmarinic acid and carnosic acid, and garlic acid in inhibiting LDL oxidation in vitro. These observations suggested a superior antiatherogeneic characteristic of tomato oleoresin over pure lycopene. The combination of lycopene with other natural antioxidants, as in tomatoes, may be more potent in inhibiting lipid peroxidation, than lycopene per se. The antiatherogenic effects of lycopene are generally believed to be due to its antioxidant properties. Dietary lycopene increases blood and tissue lycopene levels and acting as an antioxidant, lycopene traps reactive oxygen species and reduce the oxidative damage to lipids (lipoproteins and membrane lipids), proteins including important enzymes, and DNA, therapy lowering oxidative stress. This reduced oxidative stress then leads to a reduced risk for chronic diseases associated with oxidative stress such as cardiovascular disease (Omani & Aluko 2005). Alternatively, some non-oxidative mechanisms may be responsible for the beneficial effects of lycopene. The increased lycopene status in the body may regulate gene functions, improve intercellular communication, modulate hormone and immune response, or regulate metabolism, thus lowering the risk for chronic disease (Agarwl & Rao, 2000). A possible mechanism speculated for the protective role of lycopene in heart disease is via the inhibition of cellular HMGCoA reducate, the rate-limiting enzyme in cholesterol synthesis (Fuhrman *et al.,* 1997).
