Lycopene What Does It Do?

Lycopene is currently the most effective single-molecule oxygen radical scavenger among the natural antioxidants discovered, and is known as the “plant gold” [1]. Lycopene is mostly found in red, pink and orange ripe fruits and vegetables, including tomatoes, carrots, papayas, watermelons and cranberries [2-3]. It has attracted much attention due to its biological activities such as anti-oxidation, anti-inflammation and anti-cancer, and has been applied in the food industry. The Dietary Reference Intakes for Chinese Residents (2023 Edition) mentions that the recommended daily intake of lycopene for adults is 15 mg/d, but the human body cannot synthesize it and it can only be ingested from food [4]. Therefore, it is crucial to study efficient extraction methods to meet the growing demand.

Studies have shown that the content of cis and trans isomers of lycopene changes when lycopene is extracted using different extraction methods and conditions, which in turn affects the bioavailability and biological activity of lycopene. In addition, food dispersion systems and the interaction between food components and lycopene also have an important effect on the bioavailability of lycopene [5]. This article summarizes the various biological activities and mechanisms of lycopene through a systematic collection, analysis and synthesis of existing research results. It compares the principles and characteristics of different extraction methods, summarizes the effects of extraction methods and conditions on its isomerization and its application in the food industry, and provides a theoretical basis for the development of high-quality functional foods with lycopene.

1 Properties and structure of lycopene

Lycopene (C40H56) is a carotenoid with a relative molecular mass of 536.85 and a melting point of 174 °C [6]. It is insoluble in water, sparingly soluble in alcohol, and readily soluble in organic solvents such as tetrahydrofuran, trichloromethane, hexane, acetone, and petroleum ether. Lycopene is sensitive to oxidants, acids, heat, light, and metal cations such as copper and iron[7]. It is very unstable, so improper processing methods and storage conditions can easily degrade lycopene, reducing its content in the product and weakening its efficacy.

Lycopene is a straight-chain hydrocarbon containing 11 conjugated double bonds and 2 non-conjugated double bonds. It belongs to the isoprene compound family[8] and has multiple cis-trans isomers. Under the influence of light, heat or catalysts, the all-trans configuration of lycopene is converted to the cis isomer[9]. The all-trans molecule of lycopene is a fully stretched planar configuration (see Figure 1 for the structure). The methyl groups and hydrogen atoms on the carbon atoms adjacent to the double bond are prone to overlap, and the atoms at the first and fourth positions on the straight chain have non-bonding interactions. The mutual attraction of the two causes the molecular structure to bend and twist at different angles, resulting in lycopene isomerization. However, due to steric hindrance, hindered intramolecular rotation and a limited number of molecular rearrangements, only 72 different favorable conformations can be formed [10].

The most common cis isomers are 5-cis, 9-cis, 13-cis and 15-cis lycopene, and the most stable conformation is 5-cis lycopene [11]. The all-trans structure of lycopene is the most stable thermodynamic form, so most naturally occurring lycopene is in the all-trans configuration [12]. However, the bioavailability of all-trans lycopene is very low. Its special isoprene structure is very susceptible to oxidation by environmental factors during the extraction process [13], which reduces the extraction rate and bioavailability of lycopene. Studies have shown [14] that the cis-isomer of lycopene has a higher bioavailability because it is more easily digested and absorbed than the trans-isomer [15]. Therefore, lycopene is mainly in the cis-configuration (>50%) in human tissues.

2 Biological activity of lycopene

In recent years, research on the biological activity of lycopene has focused on its antioxidant, anti-inflammatory, cancer-preventing and sleep-regulating effects.

2.1 Antioxidant effect

Lycopene powder is one of the strongest antioxidants in plants [16]. The conjugated double bond system in its molecule makes it the most effective substance among carotenoids for quenching singlet oxygen [17]. Lycopene is twice as effective as beta-carotene in quenching singlet oxygen [18]. It can directly scavenge oxygen free radicals, and by promoting the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, it can inhibit lipid peroxidation and activate the endogenous antioxidant enzyme system, thereby reducing oxidative stress damage to cells and tissues (Figure 2) [19-20]. In addition, the antioxidant activity of lycopene has also been studied. For example, PATARO et al. [21] used the Fe2+ (ferric ion reducing antioxidant power, FRAP) test to measure the antioxidant capacity of lycopene in tomato skin. Pretreatment with a pulsed electric field the antioxidant activity of all-trans lycopene was improved. WANG et al. [22] compared the antioxidant activity of lycopene containing 5%, 30% and 55% cis isomers. Using DPPH and ABTS as indicators, the fifty percent inhibiting concentrations (IC50) of the samples were 140, 110, and 80 μg/mL, and 80, 60, and 35 μg/mL, respectively, indicating that the antioxidant activity of lycopene increased with the increase of the cis isomer content.

2.2 Anti-inflammatory effect

At present, research on the mechanism of lycopene's anti-inflammatory effect is still in the exploratory stage. For example, Zhang Dan et al. [23] found through animal experiments that lycopene reduces inflammation by inhibiting the activation of the nuclear factor κB (nuclear factor kappa-B, NF-κB) protein in the inflammatory pathway; it also reduces the level of serum inflammatory factors and protects the kidneys. Zhao Qinx et al. [24] studied the therapeutic effect of lycopene in combination with quercetin and curcumin on chronic prostatitis in rats and found that lycopene can reduce the expression level of inflammatory factors, inhibit the phosphorylation of NF-κB, and enhance the transcriptional activity of Nrf2 to treat prostatitis in rats.

SHEN et al. [25] studied the effect of lycopene on cardiovascular disease induced by di(2-ethylhexyl) phthalate in the hearts of specific pathogen free (SPF) grade mice. The results showed that lycopene causes an increase in cardiac glutathione peroxidase (GSH-Px) activity and an increase in cardiac glutathione (GSH) levels, which in turn suppresses the oxidative stress caused by di(2-ethylhexyl) phthalate and prevents cardiovascular disease caused by chronic inflammation.

In addition, lycopene also regulates the body's immune function through a variety of mechanisms. Studies have found that lycopene can promote the body's humoral and cellular immunity, protect phagocytes from oxidative damage, inhibit the activation of the NF-κB signaling pathway [26] and the production of inflammatory cytokines (Figure 3) [27]. These mechanisms together promote the body's immune balance, help to resist inflammation, and play an important role in maintaining health and preventing disease. However, due to the fat-soluble nature of lycopene, it has low solubility in water and is difficult to extract, resulting in low bioavailability. Therefore, some studies have constructed a lycopene delivery system such as lipid microparticles [28] to significantly improve its stability and water solubility and increase its bioavailability. In addition, a co-digestion system composed of lycopene and flavonoids can effectively enhance its absorption rate and bioavailability in the body [29].

2.3 Anti-cancer effect

Lycopene is a natural compound with potential anti-cancer effects. It can affect the cell cycle, regulate the expression of phosphorylated extracellular signal-regulated kinase proteins, change the intestinal flora, affect cancer development, and prevent colorectal cancer [30]. Lycopene can also effectively inhibit the proliferation of prostate cancer cells, promote apoptosis, prevent or treat prostate cancer by blocking gap junction molecules and inhibiting colony formation, affecting cell adhesion and migration, increasing antioxidant and anti-proliferative effects, and reducing inflammatory cytokines[31].

In addition, the possible mechanisms by which lycopene prevents esophageal cancer mainly include: improving the expression level of poly (ADP-ribose) polymerase-modified proteins (PARylation, PARy); significantly reducing the expression of inflammatory cytokines and cysteine protease proteins, inhibiting NF-κB and cyclooxygenase, and promoting apoptosis of cancer cells [32]. Zhu Yunchen et al. [33] studied the effect of lycopene on the stemness of breast cancer stem cells. The results showed that lycopene inhibited the NF-κB signaling pathway by suppressing reactive oxygen species, thereby inhibiting breast cancer stem cell stemness and enhancing its therapeutic sensitivity. In summary, lycopene exerts anticancer effects through multiple mechanisms, thereby preventing related diseases, and deserves attention and promotion in the daily diet.

2.4 Regulates sleep

Long-term consumption of lycopene-rich foods can effectively improve the cognitive and memory abilities of the elderly [34] and prevent neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease [35]. Lycopene protects the central nervous system of the brain through various mechanisms, such as inhibiting oxidative stress, improving mitochondrial function, regulating inflammatory responses, and inhibiting apoptosis [36-37], while also having a certain effect on improving sleep disorders.

EL MORSY et al. [38] found that lycopene can activate the brain-derived neurotrophic factor (BDNF) pathway, an indicator of insomnia, inhibit neuronal apoptosis, and enhance synaptic plasticity. Lycopene can also reduce the deposition of amyloid β-protein (Aβ) by inhibiting the activation of the toll-like receptor 4 (TLR4) and NF-κB (Figure 4) [39], thereby improving the neuroinflammatory response induced by it. KHAN et al. [40] investigated the relationship between sleep duration and lycopene-rich diet intake, and the results showed that a lycopene-rich diet has a positive effect on sleep regulation [41]. From a neurobiological perspective, this may be caused by the anti-inflammatory effect of lycopene, and the mechanism may be that it improves oxidative stress and activates the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway [42-43]. Under stress conditions, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system are activated for an extended period of time, resulting in HPA axis dysfunction and insomnia [44], which indicates a correlation between lycopene and sleep regulation.

3 Lycopene extraction technology

In recent years, lycopene has been used in various foods due to its excellent properties, which has attracted widespread attention to the extraction technology of lycopene. Therefore, the principles, advantages and disadvantages of the extraction technologies of lycopene are summarized and compared, as shown in Table 1.

As can be seen from Table 1, there are currently six common technologies for extracting lycopene, of which the organic solvent extraction method is the most widely used. In industrial production and laboratory extraction of lycopene, organic solvents such as petroleum ether and acetone are often used [54]. However, organic solvents are harmful to the human body and therefore cannot be used in the food industry. Supercritical CO2 extraction is a green and safe method for extracting lycopene and is expected to be used in the food and pharmaceutical industries. Secondly, auxiliary extraction techniques can improve the quality of lycopene and increase its extraction efficiency.

In addition, different extraction methods and conditions have different effects on the proportion of lycopene isomers. For example, factors such as the temperature, pressure, and solvent type used in the extraction process can affect the isomerization of lycopene [55]: high temperature and long extraction conditions usually promote thermal isomerization, while low temperature or specific solvents can help maintain the original isomeric structure of lycopene. For example, Deng Aihua et al. [56] studied the effects of supercritical extraction parameters on the yield and activity of lycopene. They found that when extracting lycopene, the yield of lycopene increased with the temperature starting at 40 °C and at pressures of 20–40 MPa. When the supercritical extraction temperature exceeded 70 °C, will have a significant effect on the antioxidant activity and composition of the lycopene isomers. Therefore, according to application requirements, the extraction conditions and processing technology should be optimized to increase the proportion of lycopene isomers and their biological activity, with a view to developing more efficient natural food ingredients and promoting their application in the food sector.

4. Application of lycopene in the food sector

Since the content of lycopene in ordinary food is low and cannot meet the needs of all types of people, the development of lycopene-enriched health foods has emerged.

4. 1 For dietary supplements

Dietary supplements are used as a supplement to the diet. They are nutritional health products that use vitamins, minerals, plant extracts, etc. as the main raw materials to supplement essential nutrients and bioactive substances for specific groups of people, to balance nutrient intake and regulate body functions [57]. At present, most dietary supplements with lycopene as the main active ingredient are in the form of soft capsules. Consuming lycopene soft capsules can effectively reduce diseases caused by free radical damage, improve immunity, and prevent disease and aging [58]. For example, Sui Jingjing et al. [59] studied the effect of lycopene ganoderma lucidum spore oil soft capsules on immune function. The results showed that consuming the soft capsules is safe and harmless, and can improve the body's immune function, providing a strong scientific basis for the development of new products. Zhao Wenfa et al. [60] investigated the hypolipidemic effect of sea buckthorn oil lycopene soft capsules on experimental hyperlipidemic rats. The results showed that the soft capsules could significantly reduce the levels of total serum cholesterol, serum triglycerides, and low-density cholesterol in the serum of hyperlipidemic rats, while having no significant effect on the level of high-density lipoprotein cholesterol. This proves that sea buckthorn oil lycopene soft capsules have a hypolipidemic effect.

4.2 For baked goods

Adding lycopene to baked goods can improve their antioxidant properties and effectively prevent a decline in nutritional quality during production, packaging, transportation and storage [61]. AHMAD BHAT et al. [62] studied the effect of lycopene on the nutritional quality and shelf life of wholemeal flour biscuits. The results showed that after the addition of the active ingredient, there were no adverse changes in the physical and sensory properties of the dough and biscuits, and the DPPH free radical scavenging activity and lipid peroxidation inhibition of the products were significantly improved. LUISA GARCÍA et al. [63] produced lycopene-enriched hamburger meat products and found that adding lycopene to hamburger meat products not only gave them a unique color, but also maintained good sensory properties. In addition, supplementing baked goods with lycopene is a potential nutritional intervention to prevent obesity, as the strong antioxidant capacity of lycopene improves lipid metabolism and prevents the formation of peroxylipids [64].

4.3 Use as a food additive

Lycopene is used in the production of meat products as a preservative substitute. Adding it to chicken not only reduces oxidation, but also effectively improves its color and texture, extending the shelf life [65]. Secondly, lycopene can also be combined with nitrites to convert nitrates into nitric oxide, reducing the residue of toxic additives in food [66]. Thirdly, lycopene can also be used as a food coloring agent in sports drinks, compound fruit juice drinks and the development of new drinks [67]. BOCKUVIENE et al. [68] developed a new water-soluble lycopene delivery system by complexing lycopene with low-molecular-weight chitosan, expanding its application in food processing. Furthermore, lycopene is also used as a natural coloring agent instead of synthetic dyes in food [69].

Chernyshova et al. [70] made a lycopene ice cream and found that the product could relieve inflammation in the body and reduce the risk of acne. In addition, oxidative stress is an important factor in the formation of peroxides. STOLL et al. [71] studied the effect of carotenoid extract poly(acid) membranes on the storage of edible oils. The results showed that the use of natural antioxidants such as lycopene to prepare active packaging is an effective way to inhibit the formation of peroxides. Finally, lycopene can also be added to edible oil as an effective dietary stabilizer to replace synthetic preservatives and inhibit oxidation during long-term storage [72].

4.4 Other applications

Lycopene is insoluble in water and is easily degraded by environmental influences. The use of microencapsulation technology can improve its stability, so that lycopene can maintain better color and storage stability during the extrusion of rice flour, cake processing and other processes. In addition, this technology can also achieve controlled or targeted release of functional ingredients. Wang Deping et al. [73] used lycopene as the core material, and cassava starch, potato starch, and high-acyl vegetable gel as the wall material ingredients to develop a new type of high-physiological-function lycopene pearl powder round soda water, which has the effect of neutralizing stomach acid. In addition, in food industry applications, it extends the tomato industry chain and promotes the comprehensive utilization and development of lycopene.

5 Summary and outlook

In summary, lycopene is an important natural plant extract with a variety of biological activities and health functions. These properties make lycopene have broad application prospects in the food industry, especially in the field of food. Its diverse applications have attracted widespread attention to the extraction technology of lycopene. When extracting lycopene, the extraction method and conditions need to be considered comprehensively to increase the proportion of the cis-isomer of lycopene, with the aim of preparing highly effective natural functional food ingredients.

At the same time, lycopene faces some problems and challenges in production and application: 1) production technology constraints [74]: the production of lycopene still has some technical difficulties, such as low extraction efficiency and high cost, which limits its large-scale application; 2) market acceptance [75]: although the health benefits of lycopene have been scientifically recognized, the market's acceptance of new functional ingredients varies, especially as it may vary between different cultures and regions; 3) regulations and standards [75]: the safety standards for food additives vary in different countries and regions, which poses a challenge to the international promotion of lycopene products; 4) single product form and function: at present, products with lycopene as the main functional ingredient mainly exist in the form of soft capsules, and their functions are mainly concentrated on enhancing the body's immunity. Other foods with bioactive applications are in urgent need of further development. With further research into the extraction technology and mechanism of lycopene, more new types of health food will appear in the future.

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