Review of the Structural Characteristics, Biological Functions, and Application Advances of Lycopene

Lycopene is a representative natural carotenoid that is widely distributed in tomatoes and tomato-based products, watermelon, guava, pink grapefruit, and other red fruits and vegetables. Among these sources, tomatoes and processed tomato products constitute the principal dietary sources of lycopene. Lycopene is an acyclic tetraterpene hydrocarbon containing an extended conjugated double-bond system, which accounts for its characteristic red color as well as its strong singlet oxygen-quenching capacity and free-radical-scavenging potential. In recent years, with the continued development of natural antioxidants, functional foods, nutritional interventions, and active-compound delivery systems, lycopene has evolved from a traditional subject of plant pigment research into an important functional molecule in food science, nutrition, pharmaceutics, and skin science.

Keywords: lycopene; carotenoid; antioxidant; functional food; natural pigment; bioavailability; delivery system

I. Basic Concepts of Lycopene

1.1 Chemical Definition and Molecular Characteristics

(1) Basic definition

Lycopene is a natural carotenoid with the molecular formula C40H56 and belongs to the tetraterpene class composed of eight isoprene units. Its molecular structure does not contain a beta-ionone ring and therefore differs from provitamin A carotenoids such as beta-carotene.

(2) Structural features

Lycopene contains multiple conjugated double bonds. This highly conjugated system constitutes the principal structural basis for its color properties, spectroscopic behavior, and antioxidant activity. Owing to this structural feature, lycopene is generally regarded as having particularly strong singlet oxygen-quenching capacity among carotenoids.

(3) Isomeric forms

In natural plant sources, lycopene is predominantly present in the all-trans configuration. However, during heat treatment, light exposure, storage, and in vivo metabolism, isomerization may occur, generating multiple cis isomers. These isomers differ in solubility, stability, and absorption behavior, which is highly relevant to nutritional evaluation and formulation development.

1.2 Source and Distribution Characteristics

(1) Plant sources

Lycopene is mainly derived from tomatoes and tomato-based products, but it is also found in watermelon, pink guava, pink grapefruit, and other plant-derived foods.

(2) Characteristics of dietary sources

From the perspective of actual dietary contribution, processed tomato products such as tomato sauce, tomato juice, and tomato paste often provide more bioavailable lycopene than fresh tomatoes. This is mainly because processing promotes cell structure disruption, pigment release, and isomer conversion.

(3) Distribution in the body

After absorption, lycopene is mainly transported by lipoproteins and accumulates in the liver, adipose tissue, adrenal glands, prostate, and other sites. This distribution pattern is one of the main reasons why lycopene continues to attract attention in studies of lipid metabolism, oxidative stress, and prostate-related biology.

II. Structural Features and Physicochemical Properties

2.1 Solubility and Stability

(1) Solubility

Lycopene is a highly hydrophobic molecule, is almost insoluble in water, and is readily soluble in lipids and certain organic solvents. Therefore, in food processing, extraction and purification, and formulation development, the lipid environment is a key determinant of its dispersion state and utilization efficiency.

(2) Stability

Lycopene is relatively sensitive to oxygen, light, heat, and metal ions, and is prone to oxidative cleavage and isomerization, which may lead to color fading and loss of activity. Accordingly, protection from light, low-oxygen conditions, and appropriate temperature control are all important during raw-material handling, sample storage, and end-product development.

(3) Dual effect of processing

Thermal processing can, on the one hand, promote the release of lycopene from plant tissues and increase its bioavailability; on the other hand, excessive processing may accelerate oxidative degradation. Therefore, optimization of processing conditions should not focus solely on increasing release efficiency, but rather on balancing release and structural stability.

2.2 Factors Affecting Bioavailability

(1) Lipid-dependent absorption

The absorption of lycopene depends on dietary lipids, bile acids, and micelle formation. In the absence of an appropriate lipid environment, intestinal absorption is often low.

(2) Food-matrix effects

Plant cell wall integrity, dietary fiber content, protein-binding state, and the type of coexisting lipids can all affect the release and absorption of lycopene from food matrices.

(3) Isomer differences

Cis isomers generally exhibit better micellar incorporation and higher bioavailability than the all-trans form. As a result, the proportion of cis-lycopene in human plasma and tissues is often higher than that in the original diet.

III. Biological Functions and Possible Mechanisms

3.1 Antioxidant Activity

(1) Singlet oxygen quenching

One of the most important biological characteristics of lycopene is its ability to quench singlet oxygen. Its long conjugated double-bond system efficiently absorbs and dissipates reactive oxygen energy, thereby reducing the risk of oxidative damage.

(2) Free-radical scavenging

Lycopene can also react with certain free radicals and reduce the propagation of lipid peroxidation chain reactions. However, in complex biological systems, its actual antioxidant effects depend not only on its intrinsic reactivity but also on concentration, microenvironment, and the broader antioxidant network.

(3) Synergy within antioxidant networks

In vivo, lycopene does not act in isolation. Rather, it participates in redox homeostasis together with vitamin C, vitamin E, glutathione, and multiple antioxidant enzyme systems. Accordingly, its function should be interpreted within the context of the integrated antioxidant network.

3.2 Regulation of Cell Signaling and Metabolism

(1) Oxidative stress-related pathways

Available evidence suggests that lycopene may influence signaling pathways related to oxidative stress and inflammation, including the Nrf2-associated antioxidant defense system and the NF-kB-associated inflammatory regulatory pathway.

(2) Regulation of lipid metabolism

Lycopene may also participate in the regulation of genes involved in cholesterol homeostasis, lipid synthesis, and fatty acid metabolism. For this reason, it has received considerable attention in studies of fatty liver disease, atherosclerosis, and metabolic syndrome.

(3) Effects on cell fate

In some cellular models, lycopene has been used to investigate its effects on cell proliferation, apoptosis, and differentiation markers. However, these findings are generally highly dependent on the specific model and experimental conditions and should not be overgeneralized.

3.3 Inflammation and Tissue-Protective Effects

(1) Regulation of inflammatory mediators

Under certain conditions, lycopene may influence the expression of inflammatory mediators and the amplification of oxidative stress-associated inflammatory responses, indicating potential utility in studies of chronic low-grade inflammation.

(2) Tissue-protection research

In experimental injury models, lycopene has frequently been used to evaluate protective effects on the liver, cardiovascular system, nervous system, and reproductive system. Common readouts include reduced lipid peroxidation, improved antioxidant enzyme activity, and attenuation of inflammatory responses.

IV. Major Application Areas

4.1 Applications in the Food Industry

(1) Use as a natural pigment

Lycopene can be used as a natural coloring component to improve food appearance and enhance red or orange-red visual characteristics. Compared with synthetic colorants, its advantages include natural origin and added functional value.

(2) Functional food development

Lycopene is widely used in the development of beverages, dairy products, soft gels, nutritional supplements, and compound functional foods intended to support antioxidant nutrition, phytonutrient supplementation, or cardiovascular health.

(3) Requirements for formulation design

Because lycopene is strongly lipophilic and highly sensitive to environmental conditions, food applications generally require coordinated optimization of the lipid phase, emulsification systems, and encapsulation technologies.

4.2 Applications in Nutrition and Health Intervention

(1) Dietary intervention studies

Lycopene intake and plasma lycopene levels are commonly used in nutritional epidemiology to evaluate relationships with oxidative stress status, lipid-metabolism indices, and the risk of certain chronic diseases.

(2) Metabolic health research

In studies of obesity, insulin resistance, and nonalcoholic fatty liver disease, lycopene is frequently used as a dietary bioactive component to evaluate its effects on lipid accumulation, inflammation, and oxidative injury.

(3) Prostate-related research

Because lycopene accumulates relatively strongly in prostate tissue, it has long attracted attention in studies of prostate nutrition and related diseases. However, the resulting evidence is more appropriately framed as mechanistic exploration and risk-associated observation rather than as a basis for simple deterministic intervention claims.

4.3 Applications in Pharmaceutics and Delivery Systems

(1) Significance for formulation development

Lycopene presents challenges including strong lipophilicity, limited stability, and restricted bioavailability. Accordingly, pharmaceutical research has primarily focused on optimization of its delivery systems.

(2) Common delivery forms

These include liposomes, nanoemulsions, solid lipid nanoparticles, microcapsules, and protein-polysaccharide composite encapsulation systems.

(3) Research objectives

The major aims are to improve dispersion stability, antioxidant protection, intestinal absorption efficiency, and storage shelf-life performance.

4.4 Applications in Cosmetics and Skin Care

(1) Antioxidant skincare direction

Because of its antioxidant potential and capacity to buffer photoinduced damage, lycopene has been used in studies of anti-pollution, anti-photoaging, and skin-barrier-protection formulations.

(2) Application limitations

Its deep color, susceptibility to oxidative degradation, and photosensitivity require the use of encapsulation, light protection, and synergistic antioxidant strategies in cosmetic systems.

V. Extraction, Preparation, and Quality Control

5.1 Extraction and Preparation Strategies

(1) Raw-material sources

Tomatoes and tomato-processing by-products, especially tomato skins and related side-stream materials, are important industrial raw materials for lycopene extraction.

(2) Extraction methods

Common methods include organic solvent extraction, supercritical fluid extraction, enzyme-assisted extraction, and combined physical approaches.

(3) Process objectives

Optimization of extraction processes should focus not only on yield, but also on control of oxidative loss, impurity removal, isomer stability, and compatibility with downstream formulation strategies.

5.2 Quality Control Considerations

(1) Content determination

High-performance liquid chromatography is commonly used for quantitative analysis of lycopene.

(2) Isomer analysis

Because different isomers differ in absorption behavior and stability, isomer distribution is also an important component of high-quality product evaluation.

(3) Stability evaluation

Quality control should include initial content, degradation rate during storage, color change, degree of isomerization, and formation of oxidation products.

VI. Key Factors Affecting Application Performance

6.1 Raw-Material and Matrix Factors

Raw-material variety, maturity, processing method, and plant tissue structure can all markedly affect lycopene content and release efficiency.

6.2 Processing and Storage Factors

Heat treatment, oxygen exposure, and light exposure all influence both lycopene release and degradation. Therefore, processing design and storage control are decisive factors.

6.3 Factors Affecting In Vivo Utilization

Dietary lipid intake, individual absorptive capacity, lipoprotein metabolic status, and dosage-form characteristics can all influence bioavailability and tissue distribution.

VII. Main Directions in Current Research

7.1 Antioxidant and Oxidative Stress Research

Lycopene is commonly used in oxidative stress models to investigate its effects on ROS levels, lipid peroxidation, antioxidant enzyme activity, and redox homeostasis.

7.2 Metabolic Health and Chronic Disease Research

Current work is focused primarily on its regulatory effects on lipid metabolism, inflammatory amplification, and oxidative injury, with particular emphasis on obesity, fatty liver disease, and cardiovascular-related phenotypes.

7.3 Formulation and Delivery System Research

Because of the limitations imposed by low stability and low bioavailability, optimization of delivery systems remains a major direction in lycopene research.

7.4 Combined Nutritional Intervention Research

Lycopene is often studied in combination with vitamin E, polyphenols, phytosterols, and other carotenoids in order to evaluate synergistic effects and the value of combined formulations.

VIII. Research and Application Considerations

8.1 Boundaries of Result Interpretation

Results from in vitro studies should not be directly extrapolated to human intervention outcomes, and epidemiological associations should not be simplistically interpreted as causal relationships.

8.2 Key Experimental Design Points

Experimental systems involving lycopene should minimize light exposure, maintain low temperature where appropriate, and reduce oxygen exposure. Proper solvent controls and vehicle controls should also be included.

8.3 Detection Strategies

If the research question involves absorption, processing effects, or delivery-system differences, reporting total lycopene content alone is usually insufficient. Isomer composition and its changes should also be evaluated.

IX. Aladdin-Related Products

9.1 Overview of Lycopene-Related Products

Catalog No.	Product Name	CAS No.	Grade and Purity
L1452550	Lycopene	502-65-8	≥95%
L465063	Lycopene	502-65-8	Moligand™, ≥98% (HPLC)

9.2 Key Reagents for Lycopene Antioxidant Evaluation, Delivery-System Construction, and Stability Control

Name	CAS No.	Experimental Stage	Principal Use	Practical Notes
Lycopene	502-65-8	Core active ingredient	Primary molecule used in antioxidant, lipid-metabolism, delivery-system, and stability studies	Should be stored protected from light, at low temperature, and under low-oxygen conditions; solution preparation and treatment procedures should minimize exposure time as much as possible
β-Carotene	7235-40-7	Carotenoid comparator	Used to compare antioxidant potency, stability, and delivery behavior among different carotenoids	Suitable for parallel design with lycopene to strengthen structure-function comparison
Lutein	127-40-2	Comparator compound	Used to compare oxidative-stress buffering capacity and encapsulation behavior in delivery systems	Suitable for combined nutritional intervention studies or carotenoid co-formulation research
Zeaxanthin	144-68-3	Comparator compound	Used to compare differences in tissue targeting and stability among lipophilic antioxidants	Particularly suitable for comparison with lycopene in lipophilic pigment systems
Vitamin E (α-Tocopherol)	59-02-9	Synergistic antioxidant studies	Used to construct lycopene-lipid-phase antioxidant networks and combined protective systems	Suitable for studies of synergistic antioxidation and lipid-phase protection; interpretation should not rely on a single endpoint alone
Ascorbic acid (Vitamin C)	50-81-7	Aqueous-phase synergistic antioxidant studies	Used to investigate water-phase/lipid-phase synergistic free-radical scavenging	Suitable for joint evaluation with vitamin E and lycopene in integrated antioxidant-network studies
Reduced glutathione (GSH)	70-18-8	Antioxidant network evaluation	Used together with lycopene to study improvement of intracellular redox homeostasis	Best interpreted together with ROS, MDA, and antioxidant enzyme activity data
N-Acetyl-L-cysteine (NAC)	616-91-1	Positive antioxidant control	Used as an antioxidant control group in oxidative-injury protection models	Better suited as a protective positive control and should not replace mechanistic interpretation of lycopene itself
DPPH	1898-66-4	In vitro free-radical scavenging evaluation	Used for rapid assessment of free-radical scavenging capacity of lycopene and lycopene formulations	Suitable for primary screening, but should not be directly extrapolated to in vivo antioxidant effects
ABTS	30931-67-0	In vitro antioxidant evaluation	Used to assess total antioxidant capacity of lycopene in different solvents or carriers	Suitable for comparing formulations and extracts, but reaction time and solvent background must be standardized
AAPH	2997-92-4	Peroxyl-radical generation	Used to establish radical-induced oxidation models for evaluating the protective effects of lycopene	Suitable for lipid-peroxidation and cell-protection experiments; blank and vehicle controls should be included simultaneously
DCFH-DA	4091-99-0	Cellular ROS detection	Used to measure total intracellular ROS changes after lycopene treatment	Suitable as an auxiliary cellular antioxidant endpoint, but does not replace direct quantification of lycopene content
1,1,3,3-Tetramethoxypropane	102-52-3	Lipid peroxidation evaluation	Used to construct MDA calibration standards and support analysis of lycopene-mediated inhibition of lipid peroxidation	Suitable for joint interpretation with ROS, SOD, and GSH data in protective-effect studies
Thiobarbituric acid (TBA)	504-17-6	Lipid peroxidation detection	Used in TBARS/MDA-related assays to evaluate the anti-lipid-peroxidation effects of lycopene	Suitable for injury models, but specificity is limited
Oleic acid	112-80-1	Lipid-metabolism model	Used to establish lipid-droplet accumulation and lipid-deposition models for evaluating the effects of lycopene on lipid metabolism	Commonly used in complex with BSA; suitable for fatty liver and obesity-related studies
Palmitic acid	57-10-3	Lipotoxicity model	Used to establish lipotoxicity models with enhanced oxidative stress and inflammation	Suitable for combined studies with lycopene to assess protective effects, but toxicity intensity must be tightly controlled
Bovine serum albumin (BSA)	9048-46-8	Fatty acid loading / vehicle control	Used to prepare oleate- or palmitate-loading systems and as a vehicle control for hydrophobic-molecule treatment	Suitable for cell models; matched BSA vehicle controls should be included
Cholesterol	57-88-5	Lipid-homeostasis studies	Used to establish cholesterol-loading models for analyzing the effects of lycopene on cholesterol homeostasis	Suitable for combination with lipid-metabolism gene endpoints and oxidative-stress readouts
Lecithin (phosphatidylcholine)	8002-43-5	Liposome construction	Used to prepare lycopene liposomes and improve dispersibility and oxidative protection	Suitable for delivery-system development; encapsulation efficiency and storage stability should be evaluated simultaneously
Cholesteryl oleate	303-43-5	Lipid-phase model / liposome modulation	Used to modulate lipid-phase membrane properties and investigate lycopene stability in lipid environments	Better suited for formulation studies and membrane-environment simulation
Polysorbate 80 (Tween 80)	9005-65-6	Nanoemulsion / dispersion systems	Used to improve aqueous dispersibility and emulsion stability of lycopene	Suitable for nanoemulsions and in vitro digestion pretreatment; concentration should be kept consistent
Poloxamer 188	9003-11-6	Nanodispersion stabilization	Used to improve dispersion stability of nanoparticle or emulsion systems	Suitable for delivery-system and storage-stability studies
Sodium alginate	9005-38-3	Microcapsule / encapsulation systems	Used to construct lycopene microcapsules and improve light protection and oxidative stability	Suitable for functional food and intestinal delivery research
Chitosan	9012-76-4	Encapsulation and interfacial protection	Used to construct polysaccharide-based encapsulation or composite delivery systems to improve stability and mucoadhesion	Suitable for combination with sodium alginate or proteins to investigate release behavior
Gelatin	9000-70-8	Microcapsule wall material	Used to construct protein-based encapsulation systems that improve processing and storage stability of lycopene	Suitable for food systems and spray-drying-related studies
β-Cyclodextrin	7585-39-9	Inclusion complexation / solubilization	Used to improve dispersibility and stability of lycopene and enhance homogeneity of treatment systems	Suitable for solubilization and protection studies, but interpretation should be combined with actual release behavior
Maltodextrin	9050-36-6	Spray-drying wall material	Used to construct powder-form lycopene encapsulation systems	Suitable for food and supplement development; content-retention rate should be measured concurrently
Gum arabic	9000-01-5	Encapsulation wall material	Used in emulsification and microcapsule wall-material studies to improve storage and processing stability	Commonly used together with maltodextrin in spray drying or composite wall-material systems
Zein	9010-66-6	Hydrophobic delivery carrier	Used to construct protein nanoparticles and improve lycopene encapsulation efficiency and controlled release	Suitable for pharmaceutical and nutritional delivery studies
Glyceryl monostearate	31566-31-1	Solid lipid nanoparticle systems	Used to construct solid lipid carriers that improve structural protection and sustained release of lycopene	Suitable for lipid-delivery studies; crystal form and encapsulation stability should be considered
Triolein	122-32-7	Oil-phase carrier	Used to construct lipid-soluble delivery systems and in vitro digestion/absorption models	Suitable for studying the effects of lipid environment on lycopene release and micellization
Medium-chain triglycerides (MCT)	65381-09-1	Delivery oil phase	Used to optimize nanoemulsion and soft-gel oil phases, improving dispersibility and processability	Better suited for formulation and oral-delivery studies
Sodium cholate	361-09-1	Micellization / digestion model	Used to establish in vitro digestion-absorption models and evaluate micellar incorporation of lycopene	Suitable for bioavailability studies; should be used together with lipid phase and digestive enzymes
Pancreatic lipase	9001-62-1	In vitro digestion model	Used to simulate intestinal lipid digestion and evaluate release of lycopene from delivery carriers	Commonly used together with sodium cholate for comparative bioavailability studies
Butylated hydroxytoluene (BHT)	128-37-0	Antioxidant protection during extraction/storage	Used to reduce oxidative degradation of lycopene during sample extraction and storage	Suitable for analytical pretreatment; the amount added should be fixed and explicitly reported
Ethoxyquin	91-53-2	Stability protection	Used to study the protective effects of antioxidants on lycopene storage stability	Better suited for process and formulation studies; applicability should match the intended use scenario

As a representative natural carotenoid, lycopene possesses not only distinctive pigment-related properties but also sustained application potential in antioxidant biology, physiological regulation, and functional-ingredient development. Its scientific value is not limited to free-radical scavenging alone, but rather lies in an integrated application system defined by its structural features, stability, bioavailability, and compatibility with delivery strategies. In food science, nutrition, pharmaceutics, and skin science, accurate understanding of the functional boundaries, processing behavior, and usage conditions of lycopene is fundamental to rigorous research and scientifically sound application.

For more related articles, please see below:

[1] Carotenoids

[2] Carotenoids: Structural Features, Dietary Sources and Research Applications – With an Aladdin Natural Pigments Product Selection Guide