New Insights into Molecular Mechanism behind Anti-Cancer Activities of Lycopene.

Lycopene is a well-known compound found commonly in tomatoes which brings wide range of health benefits against cardiovascular diseases and cancers. From an anti-cancer perspective, lycopene is often associated with reduced risk of prostate cancer and people often look for it as a dietary supplement which may help to prevent cancer. Previous scientific evidence exhibited that the anti-cancer activity of lycopene relies on its ability to suppress oncogene expressions and induce proapoptotic pathways. To further explore the real potential of lycopene in cancer prevention, this review discusses the new insights and perspectives on the anti-cancer activities of lycopene which could help to drive new direction for research. The relationship between inflammation and cancer is being highlighted, whereby lycopene suppresses cancer via resolution of inflammation are also discussed herein. The immune system was found to be a part of the anti-cancer system of lycopene as it modulates immune cells to suppress tumor growth and progression. Lycopene, which is under the family of carotenoids, was found to play special role in suppressing lung cancer.

Using Green Biosynthesized Lycopene-Coated Selenium Nanoparticles to Rescue Renal Damage in Glycerol-Induced Acute Kidney Injury in Rats.

PURPOSE: Selenium nanoparticles (SeNPs) have recently gained much attention in nanomedicine applications owing to their unique biological properties. Biosynthesis of SeNPs using nutraceuticals as lycopene (LYC) maximizes their stability and bioactivities. In this context, this study aimed to elucidate the renoprotective activity of SeNPs coated with LYC (LYC-SeNPs) in the acute kidney injury (AKI) model. METHODS: Rats were divided into six groups: control, AKI (glycerol-treated), AKI+sodium selenite (Na2SeO3; 0.5 mg/kg), AKI+LYC (10 mg/kg), AKI+LYC-SeNPs (0.5 mg/kg) and treated for 14 days. RESULTS: Glycerol treatment evoked significant increases in rhabdomyolysis-related markers (creatine kinase and LDH). Furthermore, relative kidney weight, Kim-1, neutrophil gelatinase-associated lipocalin (NGAL), serum urea, and creatinine in the AKI group were elevated. Glycerol-injected rats displayed declines in reduced glutathione level, and superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities, paralleled with downregulations in Nfe2l2 and Hmox-1 expressions and high renal MDA and NO contents. Glycerol-induced renal inflammation was evident by rises in TNF-α, IL-1ß, IL-6, and upregulated Nos2 expression. Also, apoptotic (elevated caspase-3, Bax, and cytochrome-c with lowered Bcl-2) and necroptotic (elevated Pipk3 expression) changes were reported in damaged renal tissue. Co-treatment with Na2SeO3, LYC, or LYC-SeNPs restored the biochemical, molecular, and histological alterations in AKI. In comparison with Na2SeO3 or LYC treatment, LYC-SeNPs had the best nephroprotective profile. CONCLUSION: Our findings authentically revealed that LYC-SeNPs co-administration could be a prospective candidate against AKI-mediated renal damage via antioxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic activities.

Supercritical CO2 extraction of lycopene from pink grapefruit (Citrus paradise Macfad) and its degradation studies during storage.

Lycopene was extracted from pink grapefruit using SC-CO2 and rice bran oil as co-solvent. Response surface methodology was employed to evaluate the individual and interactive effects of three process parameters varied at five levels i.e. pressure (250, 300, 375, 450 & 500 bar), temperature (55, 60, 70, 80 & 85 °C), and extraction time (60, 90, 135, 180 & 210 min). Single optimum point for multiple response variables was achieved at 325 bar, 64 °C, and 143 min with overall desirability of 0.92 at which 70.52 ± 3.65% (lycopene extraction efficiency) and 11154 ± 148 ppm (γ-oryzanol) were predicted. Extraction temperatures of more than 80 °C and time beyond 180 min led to the isomerization of lycopene. Lycopene storage at 3 °C, 10 °C, & 25 °C showed average k and half-life values as 0.018, 0.030, & 0.075 and 40, 23, & 9 days, respectively for first-order degradation kinetics; depicting faster degradation at higher storage temperatures.

Fabrication of Pickering emulsion based on particles combining pectin and zein: Effects of pectin methylation.

Although the stabilization of Pickering emulsions based on the interaction of pectin and zein is known to be effective, the effects of the degree of methylation (DM) of pectin on the stability of Pickering emulsions remains unclear. In the present study, pectin/zein particle dispersions (PZDs) were fabricated by anti-solvent precipitation based on different DM values of pectin (13.70 %-71.42 %). Differential Scanning Calorimetry (DSC) curves and Fourier transform infrared spectroscopy (FTIR) confirmed the methyl ester carbonyl and carbonyl groups significantly affected the formation of hydrogen bonds, which consequently resulting in the secondary conformation of PZDs as reflected by circular dichroism (CD). The PZDs fabricated by pectin with DM values higher than 35.50 % formation of the network between the barriers of the droplets, showed high stability against pH (3.0-9.0) and Ca2+ (60-300 mM) at an oil fraction (φ) of 0.60. Furthermore, the Pickering emulsions showed good lycopene protective effects.

Synergistic Effects of Food Ingredients and Vegetable Oils on Thermal Isomerization of Lycopene.

Recent investigations have demonstrated that some food ingredients and vegetable oils, such as onion, garlic, and sesame oil, enhanced thermal Z-isomerization of (all-E)-lycopene in tomatoes. However, the synergistic effects of these ingredients and oils have not yet been investigated. This study aims at clarifying how the combined use of lycopene Z-isomerization-promoting food ingredients and vegetable oils impacts thermal Z-isomerization of (all-E)-lycopene in tomato puree. Apart from a few exceptions, when olive oil was used as a reaction medium, the combined use of garlic, cabbage, broccoli, shiitake mushroom, and makonbu improved the total Z-isomer ratio of lycopene after heating compared to the separate use of the tested ingredients. However, when onion was used together with the other ingredients, the Z-isomer ratio significantly decreased compared to its individual use. Moreover, when garlic, cabbage, broccoli, shiitake mushroom, and makonbu were used with sesame and mustard oils, that exhibit higher Z-isomerizationpromoting effect than that of olive oil, the lycopene Z-isomerization reaction was further enhanced. However, when onion was combined with these oils, the Z-isomer ratio decreased compared to that measured upon the combined use of onion with olive oil. Our results on these synergistic effects are not only important for the food and drink manufacturing industries but also for daily home cooking.

Versatile Nutraceutical Potentials of Watermelon-A Modest Fruit Loaded with Pharmaceutically Valuable Phytochemicals.

Watermelon (Citrulus lantus) is an important horticultural crop which belongs to the Curcubitaceae family. The nutraceutical potential of watermelon has been illustrated by several researchers, which makes it a better choice of functional food. Watermelon has been used to treat various ailments, such as cardio-vascular diseases, aging related ailments, obesity, diabetes, ulcers, and various types of cancers. The medicinal properties of watermelon are attributed by the presence of important phytochemicals with pharmaceutical values such as lycopene, citrulline, and other polyphenolic compounds. Watermelon acts as vital source of l-citrulline, a neutral-alpha amino acid which is the precursor of l-arginine, an essential amino acid necessary for protein synthesis. Supplementation of l-citrulline and lycopene displayed numerous health benefits in in vitro and in vivo studies. Similarly, the dietary intake of watermelon has proven benefits as functional food in humans for weight management. Apart from the fruits, the extracts prepared from the seeds, sprouts, and leaves also evidenced medicinal properties. The present review provides a comprehensive overview of benefits of watermelon for the treatment of various ailments.

Potential Role of Lycopene in the Prevention of Postmenopausal Bone Loss: Evidence from Molecular to Clinical Studies.

Osteoporosis is a metabolic bone disease characterized by reduced bone mineral density, which affects the quality of life of the aging population. Furthermore, disruption of bone microarchitecture and the alteration of non-collagenous protein in bones lead to higher fracture risk. This is most common in postmenopausal women. Certain medications are being used for the treatment of osteoporosis; however, these may be accompanied by undesirable side effects. Phytochemicals from fruits and vegetables are a source of micronutrients for the maintenance of bone health. Among them, lycopene has recently been shown to have a potential protective effect against bone loss. Lycopene is a lipid-soluble carotenoid that exists in both all-trans and cis-configurations in nature. Tomato and tomato products are rich sources of lycopene. Several human epidemiological studies, supplemented by in vivo and in vitro studies, have shown decreased bone loss following the consumption of lycopene/tomato. However, there are still limited studies that have evaluated the effect of lycopene on the prevention of bone loss in postmenopausal women. Therefore, the aim of this review is to summarize the relevant literature on the potential impact of lycopene on postmenopausal bone loss with molecular and clinical evidence, including an overview of bone biology and the pathophysiology of osteoporosis.

Production of (Z)-Lycopene-Rich Tomato Concentrate: A Natural Catalyst-Utilized and Oil-Based Study for Practical Applications.

Since lycopene Z-isomers exhibit greater bioavailability and biological activity than the naturally occurring all-E-isomer, efficient manufacturing methods for (Z)-lycopene-rich materials are urgently needed. Herein, a method was developed for Z-isomerization of (all-E)-lycopene in tomato oleoresin using heat treatment and a natural catalyst, viz. allyl isothiocyanate (AITC). For practical application of this isomerization technology, no organic solvents were used, and instead, oils and fats were used as the reaction medium. The Z-isomerization of (all-E)-lycopene was promoted by heating (>120 °C) even when oil and fat media were used. Allyl isothiocyanate enhanced thermal Z-isomerization and improved the (5Z)-lycopene content, which shows higher biological activity compared to the other Z-isomers. The thermal isomerization efficiency with AITC was further improved by using certain vegetable oils such as argan and olive oils. In addition, the storage stability of (Z)-lycopene-rich tomato concentrates dispersed in olive oil was evaluated. The total Z-isomer ratio and lycopene concentration decreased with longer storage periods, and it was revealed that (5Z)-lycopene showed excellent storage stability among the mono-Z-isomers.

Extraction of Carotenoids from Tomato Pomace via Water-Induced Hydrocolloidal Complexation.

Agro-industrial waste is a largely untapped natural resource of bioactive compounds including carotenoids and pectin. However, conventional solvent extraction involves the excessive use of organic solvents, costly equipment, and tedious operation. These limitations of conventional extraction methods could be prospectively overcome by the carotenoid-pectin hydrocolloidal complexation. The complexation of lycopene and pectin was efficiently promoted in an aqueous environment, resulting in the colloidal complexes that can be subsequently recovered by sedimentation or centrifugation. In this study, the potential of carotenoid-pectin complexation on tomato pomace containing carotenoids and pectin was evaluated. Tomato pomace is a rich source of lycopene, ß-carotene as well as pectin, making it suitable as the raw material for the carotenoid extraction. The extraction of carotenoid and pectin from tomato pomace was optimized using response surface methodology. The maximum recovery was 9.43 mg carotenoid fractions/100 g tomato pomace, while the purity of carotenoid-rich fractions was 92%. The antioxidant capacity of carotenoids extracted from the complexation method was found to be higher than that from the solvent extraction method. Moreover, extraction yield and antioxidant capacity of carotenoid obtained from the carotenoid-pectin complexation were comparable to that from solvent extraction. The carotenoid-pectin complexation is a promising green approach to valorize agro by-products for the extraction of valuable carotenoids.

Enhanced Lycopene Extraction from Tomato Peels by Optimized Mixed-Polarity Solvent Mixtures.

Mounting evidence from clinical and epidemiological studies suggests that lycopene, the most abundant carotenoid in tomatoes, may be beneficial in the prevention or treatment of some important diseases. Ripe tomato peels are the richest source of lycopene, but the use of conventional solvent extraction methods without pretreatment of the plant material results in very poor recovery. The reason lies in the localization of lycopene in the plant tissue and the low permeability of the latter to solvent molecules. In this paper, a mixture design procedure was used to formulate solvent mixtures allowing the recovery of lycopene from non-pretreated tomato peels. Two ternary systems were investigated: (a) n-hexane-ethanol-acetone and (b) ethyl lactate-ethanol-acetone. Optimization of the ternary mixture composition led to a recovery of over 90% of the lycopene present in the peels. The high extraction efficiency was explained in terms of lycopene affinity combined with the ability to swell the plant material. A tomato oleoresin with high antioxidant activity and a lycopene content of about 13% (w/w) was also produced. Overall, the results indicate that highly effective solvents for direct recovery of lycopene from tomato peels can be easily prepared by a mixture design approach.

Impact of onions in tomato-based sauces on isomerization and bioaccessibility of colorless carotenes: phytoene and phytofluene.

Onions as an interesting ingredient have been proved to promote Z-isomerization of lycopene and increase bioaccessibility of total-lycopene. Phytoene (PT) and phytofluene (PTF), the precursors of lycopene, are colorless carotenes, which are attracting much attention and are also abundant in tomatoes. Therefore, onions might also affect the distribution and bioaccessibility of PT and PTF isomers during heating tomato (hot-break and cold-break purees)-onion-extra virgin olive oil (EVOO) sauces. The addition of onions (or diallyl disulfide present in onions) into tomato purees did not cause degradation of PT or PTF; however it favored E/Z-isomerization of PT and PTF by reducing the proportions of their natural Z-isomers (Z-15-PT and Z2,3-PTF) and decreased the bioaccessibility of total-PT and total-PTF. Simultaneously, a complex picture was obtained for the effect of onions on the bioaccessibility of individual PT and PTF isomers, depending on the precise isomer. Bioaccessibility of PT and PTF isomers in tomato-based sauces decreased in the order: 15-Z-PT > all-E-PT; Z2,3-PTF > all-E-PTF > Z4 or Z5-PTF; total-PT > total-PTF. E-isomerization of PT and PTF enhanced by onions during heating tomato-onion purees decreased their bioaccessibility.

Influence of ß-Carotene and Lycopene on Oxidation of Ethyl Linoleate in One- and Disperse-Phased Model Systems.

The induction period (IP) of ethyl linoleate stressed at 60 °C was monitored via the formation of hydroperoxides. The addition of lycopene (1% w/w) increased the IP from 7.0 to 10.0 h to prove the strong antioxidative potential in contrast to ß-carotene with pro-oxidative effects (IP: 6.0 h), both showing strong scavenging activity under fast degradation. When peroxidation was induced by singlet oxygen, both carotenoids effectively inhibited the formation of hydroperoxides, with quenching activity only observed at low singlet oxygen concentrations, while scavenging still dominated. Thus, carotenoids did not interact with the introduced singlet oxygen but rather with the radical intermediates of fat oxidation. These experiments were then transferred to lecithin-based micelles more related to biological systems, where singlet oxygen was generated in the outer aqueous phase. Lycopene and ß-carotene delayed or inhibited lipid peroxidation depending on concentration. In this setup, ß-carotene showed exclusively quenching activity, while lycopene was additionally degraded to about 70%.

Supercritical CO2 extraction of tomato pomace: Evaluation of the solubility of lycopene in tomato oil as limiting factor of the process performance.

This work considered lycopene (lyc) amount and (all-E)-lyc:Z-lyc (E:Z) ratio as driving parameters of the tomato pomace (TP) supercritical CO2 extraction (SFE_CO2) performance. By testing lyc concentrations solubilization in tomato seed oil and E:Z ratios of 75:25, 59:39 and 25:75, full and partial equations (SE) were calculated. The application of mass balances to experimental TP_SFE_CO2 highlighted an extraction yield of 84.6% TP lyc, although the recovery into the extract was 48.4% of the extracted lyc (lyc = 1339 µg g-1 oil). The SE application to TP_SFE_CO2 data confirmed that partial solubilization mainly depended on oil availability vs. lyc amount. Thus an improved TP_SFE_CO2 was designed in which 703 g of exogenous tomato oil will be fluxed from the co-solvent tank: the new process will produce 884 g kg-1 d.m. of extract with an expected recovery of 99.3% of the extractable lyc (lyc = 502 µg g-1 oil).

Effect of tomato (Solanum lycopersicum L.) lycopene-rich extract on the kinetics of rancidity and shelf-life of linseed (Linum usitatissimum L.) oil.

The effect of tomato lycopene-rich extract (TLE) addition on shelf-life of linseed oil was evaluated. Linseed oil was extracted by cold pressing and TLE by supercritical CO2. Linseed oils with and without TLE addition were characterized for moisture, color, refractive index, fatty acid composition and antioxidants. Adding TLE to 80 mg lycopene/kg oil improved linseed oil stability, showing the same induction time at 110 °C (by Rancimat) of control linseed oil with 200 mg/kg butylhydroxytoluene. The increase of free fatty acid, peroxide value, p-anisidine value, K232 and K268 at 40, 50, and 60 °C until 90 days followed first-order kinetics. Rancidity rate augmented with temperature. TLE addition slowed oil degradation without changing the mechanism since the Arrhenius lines were parallel. Mean Ea were respectively 38.2, 24.7, 38.0, 38.2, 41.5 kJ/mol. TLE addition increased linseed oil shelf-life by 31% (Rancimat) and by 42% (stability kinetics during storage).

Se Nanoparticles Induce Changes in the Growth, Antioxidant Responses, and Fruit Quality of Tomato Developed under NaCl Stress.

Nanotechnology represents an opportunity to improve the use of elements in agriculture. Selenium is an element that is beneficial to plants and essential to the human diet. The size of nanoparticles gives them characteristics that can enhance the benefits that selenium provides to plants. The objective of the present study was to determine the effects of selenium nanoparticles on the growth, antioxidant responses, and fruit quality of tomato developed under NaCl stress. Four doses of selenium nanoparticles (1, 5, 10, and 20 mg L-1) under NaCl stress, only NaCl, and a control were evaluated. The results showed that the impact of salinity on the growth of the tomato crop can be reduced with the application of selenium nanoparticles. However, the amount of both enzymatic and non-enzymatic compounds significantly increased in the leaves and fruits of tomato. The results suggest that the application of selenium nanoparticles generated a positive effect against salinity in the tomato crop; moreover, it had a positive impact on the content of beneficial biocompounds for human health in tomato fruits.

A D-optimal mixture design of tomato-based sauce formulations: effects of onion and EVOO on lycopene isomerization and bioaccessibility.

A D-optimal mixture design was used to study the effects of onion and extra virgin olive oil (EVOO) on lycopene Z-isomerization, lycopene diffusion into oil (expressed as a partition factor between tomato-based puree and oil) and in vitro bioaccessibility of lycopene isomers after thermal treatment of tomato-based puree consisting of tomato (75-100%), onion (0-20%) and EVOO (0-5%). A decrease of tomato puree could improve lycopene Z-isomerization, lycopene diffusion and lycopene bioaccessibility. The component interactions had an important influence on the Z-isomerization of lycopene, besides the linear mixtures of components. However, only linear mixtures of components appeared to have significant effects on the diffusion and bioaccessibility of lycopene, in which EVOO had the highest positive effect followed by onion. The bioaccessibility of lycopene isomers in every tomato-based sauce formulation decreased in the order: 13-Z-lycopene > 9-Z-lycopene > 5-Z-lycopene > all-E-lycopene. The bioaccessibility of total-Z-lycopene was at least 10 times higher than that of all-E-lycopene. Proportions of total-Z-lycopene were correlated positively with the partition factor and bioaccessibility of total-lycopene, with an r over 0.730 (p = 0.0031). Therefore, increased Z-lycopene proportions probably contributed to enhanced lycopene diffusion and bioaccessibility. The positive effects of components, especially onion, on total-lycopene diffusion and bioaccessibility were probably because the components increased the Z-isomerization of lycopene during heating of tomato-based puree.

A facile water-induced complexation of lycopene and pectin from pink guava byproduct: Extraction, characterization and kinetic studies.

The redfleshed pulp discarded from pink guava puree industry is a rich source of lycopene and pectin. In this study, we developed a facile extraction process employing water as the primary extraction medium to isolate the lycopene and pectin from pink guava decanter. When the decanter was suspended in water, the complexation of lycopene and pectin formed the cloudy solution, where the colloidal complexes were recovered through centrifugation. The presence of lycopene and pectin in the complex was confirmed by the spectroscopic, microscopic and chromatographic analyses. The lycopene fractionated from the complexes had a purity level of 99% and was in all-trans configuration. The colloidal complexes yielding the highest concentration of lycopene was obtained at pH 7, 1% (w/v) solid loading and 25 °C. The experimental data of time-course extraction of lycopene-pectin complex were best fitted with two-site kinetic model, hinting the fast- and slow-release phases in the extraction process.

Heating tomato puree in the presence of lipids and onion: The impact of onion on lycopene isomerization.

Z-lycopene isomers are more bioavailable than all-E-lycopene, especially 5-Z-lycopene. Based on our observations, the addition of unblanched onion could favor Z-isomerization of lycopene (by more than 94%) during heating tomato-onion-extra virgin olive oil (EVOO) purees at 90 °C for 2 h. The increase in Z-lycopene was correlated linearly with the addition of unblanched onion, with R2 > 0.92, and increased rates of 5-Z-lycopene were 3-4 times higher than for 9-Z-lycopene and 13-Z-lycopene. Diallyl disulfide (DADS), formed by alliinase-catalyzed breakdown of non-volatile precursors in onion, contributed to these increases and correlated linearly (R2 > 0.79, 0-0.50 mg/g puree) with increased Z-lycopene. Increased rates of 5-Z-lycopene were also 3-4 times higher than for 9-Z-lycopene and 13-Z-lycopene. However, blanching of onion, in tomato-onion-EVOO purees, before heating, significantly decreased the effect of onion on Z-isomerization of lycopene.

Enhanced Z-isomerization of tomato lycopene through the optimal combination of food ingredients.

In tomatoes, most lycopene is present in the all-E-configuration and shows very low bioavailability, whereas the Z-isomers show higher bioavailability. Hence, for health reasons, it is expected that the ingestion of lycopene Z-isomers is preferable. Very recently, it was reported that onion and possibly garlic promoted thermal Z-isomerization of (all-E)-lycopene but there are no reports for other food ingredients. Here we show new food ingredients that enhance thermal Z-isomerization of lycopene in tomatoes and from the results, we guessed some causative components having the Z-isomerization promoting effect. A comprehensive investigation of food ingredients revealed that some vegetables (Allium sp., Brassica sp., and Raphanus sp.), shiitake mushroom (Lentinus edodes), and some edible seaweeds (Saccharina sp. and Ecklonia sp.) markedly promoted Z-isomerization of (all-E)-lycopene in tomato puree with heating at 80 °C for 1 h. Moreover, it was revealed that polysulfides, isothiocyanates, carbon disulfide, and iodine, which were commonly contained in the above food ingredients in considerable quantity, enhanced thermal Z-isomerization of (all-E)-lycopene. Our findings on the food ingredients and the food-derived catalysts having a carotenoid Z-isomerization promoting effect are important, not only for the food, drink, and dietary supplement manufacturing industries, but also for daily home cooking.

Plant-Derived Bioactives in Oral Mucosal Lesions: A Key Emphasis to Curcumin, Lycopene, Chamomile, Aloe vera, Green Tea and Coffee Properties.

Oral mucosal lesions have many etiologies, including viral or bacterial infections, local trauma or irritation, systemic disorders, and even excessive alcohol and tobacco consumption. Folk knowledge on medicinal plants and phytochemicals in the treatment of oral mucosal lesions has gained special attention among the scientific community. Thus, this review aims to provide a brief overview on the traditional knowledge of plants in the treatment of oral mucosal lesions. This review was carried out consulting reports between 2008 and 2018 of PubMed (Medline), Web of Science, Embase, Scopus, Cochrane Database, Science Direct, and Google Scholar. The chosen keywords were plant, phytochemical, oral mucosa, leukoplakia, oral lichen planus and oral health. A special emphasis was given to certain plants (e.g., chamomile, Aloe vera, green tea, and coffea) and plant-derived bioactives (e.g., curcumin, lycopene) with anti-oral mucosal lesion activity. Finally, preclinical (in vitro and in vivo) and clinical studies examining both the safety and efficacy of medicinal plants and their derived phytochemicals were also carefully addressed.