Study on CIS Lycopene

In 1903, Schunck studied the absorption spectrum of lycopene and compared it with the absorption spectrum of carotene. He found that the two absorption spectra were significantly different, and officially named it lycopene. Lycopene lacks the β-ionone ring structure and has no physiological activity of vitamin A. Therefore, lycopene has strong anti-cell proliferation ability and can reduce the incidence of cancer, cardiovascular disease, etc., regulate immunity, and delay aging. Currently, lycopene is mainly used in two ways: as a food coloring agent or a highly effective food antioxidant; and as a functional food or health food to prevent cancer. However, because lycopene is unstable, the lycopene in plants is all all-trans, while in various tissues of the human body, it is mainly the cis isomer, which is therefore more easily absorbed by the body. This article summarizes the structure, physiological function, and effect of lycopene isomerization on its physiological activity of lycopene, as well as the common types of lycopene isomerization reactions (thermo-induced, thermo-promoted, and photo-induced isomerization reactions) at home and abroad, providing a theoretical basis for the development of high-physiological-activity lycopene products.

1. Structural characteristics of lycopene

Lycopene is a kind of carotenoid with remarkable physiological activity, and is abundant in ripe tomato fruits and tomato products. The molecular formula of lycopene is C40H56, molecular weight 536.85, melting point 174 °C (trans), dark red needle-like crystals, and it is fat-soluble. Lycopene's two non-conjugated C-C double bonds and 11 conjugated double bonds result in poor stability [1], and it is prone to oxidative degradation or cis-trans isomerization. The structure of lycopene is shown in Figure 1.

Lycopene has a total of 11 conjugated double bonds, so intramolecular rotation is not possible, and due to the steric hindrance effect, the number of molecular rearrangements is limited, so there are only 72 cis isomers, rather than the theoretical 2,048 [2].

2 Physiological functions of lycopene

2.1 Anti-aging

Lycopene has strong in vitro singlet oxygen quenching ability (quenching rate constant kq= 31×109 M-1 ·s-1) and the effect of scavenging peroxyl radicals. Compared with other carotenoids, the kq value of lycopene is 100 times that of α-carotene and 2.2 times that of β-carotene. Lycopene can react with active oxygen fragments such as H2O2 and NO2, inhibiting damage to lymphocyte membranes or cell death caused by NO2 free radicals, and thus delaying the aging process [3].

2.2 Cancer prevention

Studies have shown that lycopene has a preventive effect against 13 types of cancer, and that lycopene intake has been found to be negatively correlated with cancer incidence [3-4]. Randomized controlled studies in the health care sector have confirmed that tomatoes and tomato products reduce the risk of prostate cancer. Edward Giovannucci et al. [5] have experimentally demonstrated that other carotenoids do not have this effect, and pointed out that lycopene reduces the risk of cancer by increasing the concentration of prostate-specific antigen and increasing the mortality rate of apoptotic cells in tumors. The main mechanism of carcinogenesis is the inhibition or destruction of communication between intercellular connections, and lycopene can induce this communication function to prevent carcinogenesis. Nancy J. Engelmann et al. [6] found that in addition to lycopene, hexahydrolycopene and octahydrolycopene may also play a vital role in cancer prevention.

2.3 Prevention of cardiovascular disease

Cardiovascular disease is responsible for one third of all deaths worldwide each year. However, the mortality rate from cardiovascular disease in the Mediterranean region is very low, because the “Mediterranean diet” is rich in plant nutrients, the main functional substance of which is lycopene [7]. Howard et al. [8] conducted a long-term test on nearly 40,000 middle-aged and elderly women to observe the relationship between lycopene intake and cardiovascular disease. The results showed that eating foods high in lycopene (such as ketchup and sauce) or foods mixed with tomato and oil is more beneficial for the prevention of cardiovascular disease. Lycopene can prevent the oxidation of low-density lipoprotein and the synthesis of cholesterol, thereby reducing the amount of lycopene in the blood [9], which has the same effect as drugs used to treat cardiovascular disease and hyperlipidemia.

3 The effect of lycopene isomerization on its physiological activity

Lycopene present in natural plants is mostly trans, but in animals and humans, the proportion of cis increases and the proportion of trans decreases. The content of cis isomers in human blood is over 60%. Most trans isomers are converted to cis during digestion in the gastrointestinal tract. Trans isomers are prone to precipitate and form crystals, which affect absorption.

Lycopene's conjugated double bond makes it unstable and prone to isomerization, but this is also the basis for its physiological function. Isomerization of lycopene is mostly caused by factors such as light, heat, and acid. When isomerization occurs and lycopene becomes cis, mainly in the following aspects: first, the cis isomer has a lower melting point; second, the cis isomer is more easily soluble; third, the cis isomer has stronger antioxidant activity; fourth, the cis isomer is more easily absorbed by the body; and fifth, the cis isomer has absorption at shorter wavelengths and is less able to form color than the trans isomer.

4 Lycopene isomerization methods

The cis-isomerization of lycopene is of significant importance in enhancing the physiological activity of lycopene and reducing the risk of disease [10-13]. The common types of lycopene isomerization reactions are mainly thermo-induced, thermo-promoted and photo-induced isomerization reactions.

4.1 Thermo-induced isomerization reaction

Lycopene can be rapidly converted from all-trans to cis under certain conditions or when heated in an organic phase. This reaction is called thermo-induced isomerization. Patent EP 1358139 A1 [14] discloses a method for extracting cis lycopene in an organic phase by heating and refluxing, which extracts 5-cis lycopene with a low content and is a cumbersome process that takes a long time. In addition, Li Hong [15] used conventional heating with ethyl acetate and high-temperature heating with ethyl lactate to carry out the isomerization reaction, It was found that the cis configuration ratio could reach 78% to 85% after 10 to 12 hours of reaction. Zhang Lianfu et al. [16] used a short-time thermal reflux/cholate adsorption-separation-recovery solvent process. After 5 to 10 hours of reaction, the cis configuration ratio of lycopene reached 65% to 95%.

Wu Dacheng et al. [17] mixed tomato sauce with cooking oil, heated, filtered, and then evaporated the clear liquid by heating in a circulation process. After condensation and reflux, the cis content in lycopene reached 11.5% to 48.1%. Honda et al. [18] used CHCl3 as a solvent for a thermally induced isomerization reaction. After 24 hours, the total cis-lycopene content was 48.4%; Zhang et al. [19] refluxed lycopene with ethyl acetate as the solvent for 24 h, and the total cis-lycopene content was 49.9%; Colle et al. [20] heated tomato paste to increase the cis-lycopene content. The cis ratio can reach 15% when heated at temperatures below 140 °C. In another study by Colle et al. [21], the same method was used, with olive oil as the oil carrier for the tomato sauce, and the heating treatment was carried out. This method can increase the total cis content to 28.5% to 55.2%. The above studies show that direct heating can promote the isomerization of lycopene, but the heat treatment process not only easily degrades lycopene, but also has a serious impact on the quality of lycopene-related products, greatly limiting its scope of application.

4.2 Isomerization promoted by heat

Isomerization promoted by heat refers to the reaction of isomerization of lycopene in an organic phase using a catalyst. Liu Qinghui et al. [22] used ethylene glycol and sec-butyl alcohol as the lycopene isomerization solvents, and sodium sulfate and sodium bisulfite as the co-catalysts to carry out the lycopene isomerization experiment. The results showed that the isomerization effect was better when ethylene glycol and sodium sulfate were used as solvents. Honda et al. [23] used acetone as the solvent and FeCl3 as the catalyst. After reacting for 3 h, the cis-lycopene ratio reached 79.9%. Because the catalyst added to the reaction is highly oxidizing, it is difficult to remove it from the reaction product, which severely limits the production and practical application of lycopene isomerization products.

4.3 Photochemical isomerization reaction

Lycopene powder is treated under direct light or the catalysis of a photosensitizer to produce lycopene isomerization. This process is called photoisomerization. Treatment under direct light conditions is to place lycopene under certain temperature and wavelength conditions and isolate it from oxygen to cause cis-trans conversion of the double bond group. Wang Xuesong et al. [24] used direct photochemical synthesis technology to irradiate with a 450 W high-pressure mercury lamp under nitrogen protection through a cut-off filter that could cut off different wavelengths, and controlled the reaction temperature to obtain 73% cis isomers. This method has high yield of cis isomers, but there are problems such as high cost and easy production of by-products. Photochemical isomerization reactions using photosensitizers as catalysts mainly use iodine as the catalyst. For example, Zechmeister L et al. [25] have carried out related research that can increase the cis isomer content to 80%. However, this reaction requires a special device, so it is difficult to apply in practice.

At present, research on the isomerization of lycopene at home and abroad mainly focuses on three types of reactions: thermo-induced, thermo-promoted and photo-induced isomerization reactions. However, these three reaction types all have certain disadvantages. In the future, an isomerization treatment method should be found that can not only increase the content of cis-isomers, but also be simple to operate and low in cost.

5 Outlook

Lycopene powder is one of the most important antioxidant nutrients, but its bioavailability is very low, which is related to its physiological activity and specific isomers. At present, there are many functional studies on lycopene, but there is very limited research on lycopene isomerization. Therefore, studying an efficient lycopene isomerization process can help improve the absorption and utilization of lycopene in the body.

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