Lycopene in hydrophobic deep eutectic solvent with natural catalysts: A promising strategy to simultaneously promote lycopene Z-isomerization and extraction.

Lycopene Z-isomerization and degradation in a series of hydrophobic natural deep eutectic solvents (HNDES) was firstly studied. The highest lycopene retention (about 84.6%) was found in HNDES composed of thymol and menthol (TM), and fatty acid-based HNDES promoted lycopene Z-isomerization (about 70% for total Z-isomers) and degradation. The addition of allyl isothiocyanate (AITC), diallyl disulfide (DADS) and capric acid into TM promoted Z-isomerization of lycopene (80% for total Z-isomers), especially 5Z-isomer (>30%), while lycopene remaining rate in TM/-capric acid was below 20%. During lycopene extraction from tomato power and watermelon juice by TM, the ratios of Z-isomer significantly (p < 0.05) increased especially with AITC and DADS (up to about 80%), and extraction yields increased even > 100% with capric acid. Lycopene in TM/-capric acid extracts showed low degradation with Z-isomers increasing during storage. TM with capric acid could simultaneously promote lycopene Z-isomerization and extraction.

Lycopene protects against Bisphenol A induced toxicity on the submandibular salivary glands via the upregulation of PPAR-γ and modulation of Wnt/ß-catenin signaling.

BACKGROUND AND AIM: The submandibular salivary glands (SMG) represent a suitable model for studying epithelial cell growth and differentiation. Bisphenol A (BPA) is a xenoestrogen, synthesized to produce polymers such as polycarbonates and epoxy resins. There are concerns about the occurrence of BPA in food, water as well as its appearance in human tissues and body fluids. Lycopene (LYC) is a carotenoid compound that exerts antioxidant and anti-inflammatory properties. This work was performed to study possible protective effect of LYC against BPA toxicity in SMG. MATERIAL AND METHODS: 40 albino rats were divided into 4 groups; Group I: served as controls. Group II: rats received LYC (4 mg/kg, p.o), Group III: rats received BPA (10 mg/kg, p.o) and Group IV: rats received LYC (4 mg/kg, p.o) and BPA (10 mg/kg, p.o). All drugs were administered for 45 days then under anesthesia, rats were sacrificed. The SMG specimens were taken for histological and biochemical studies. RESULTS: BPA resulted in a significant rise of malondialdehyde, tumor necrosis factor-α and interleukine-1ß. In contrast, the tissue levels of glutathione and PPAR-γ were significantly decreased. BPA activated Wnt/ß-catenin pathway evidenced by upregulating WNT3a, ß-catenin and c-myc expression. Moreover, SMG of BPA showed degenerative changes that affected the parenchymal and stromal elements of the glands. The immunohistochemical localization of cytokeratin 5,6 and 18 of BPA rats revealed weak immunostaining of the serous secretory cells, myoepithelial cells and ductal cells. Upon treatment with LYC, glutathione and PPAR-γ were restored. CONCLUSION: LYC acted as a protective agent against BPA-induced pathological changes in SMG.

Stability and digestibility of encapsulated lycopene in different emulsion systems stabilized by acid-modified soybean lipophilic protein.

BACKGROUND: Owing to the harsh acidic environment of the stomach, acid-resistant emulsion products have wide-ranging applications in the food industry. Herein, natural soybean lipophilic protein (LP) was used to establish coarse emulsions, nanoemulsions, emulsion gels, and high internal phase Pickering emulsions (HIPPE) under acidic conditions. Furthermore, the carrying characteristics of the acid-resistant emulsion system with lycopene were explored. RESULTS: Comparisons of particle sizes, potentials, microstructures, and rheology of the four carrier systems revealed that HIPPE has a single particle-size distribution, the largest zeta potential, and an elastic gel-like network structure. Comparison of encapsulation rates indicated that HIPPE had the best effect on encapsulating lycopene, reaching approximately 90%. The pH stability, storage stability, and simulated in vitro digestion experiments showed that the four emulsions that were stable under acidic conditions had good acid resistance. Among them, the acid-induced LP-stabilized HIPPE had the best storage stability and superior compatibility with the harsh acidic environment of the stomach, which not only achieved the purpose of delaying the release of lipids but also conferred better protection to lycopene in the gastric tract; moreover, it achieved the best bioavailability. CONCLUSION: LP-stabilized HIPPE has the best stability and can yield better absorption and utilization of lycopene by the body. The results of this study are helpful for the development of acid-resistant functional emulsion foods that are conducive to the absorption of lycopene. © 2022 Society of Chemical Industry.

Removal of lycopene substrate inhibition enables high carotenoid productivity in Yarrowia lipolytica.

Substrate inhibition of enzymes can be a major obstacle to the production of valuable chemicals in engineered microorganisms. Here, we show substrate inhibition of lycopene cyclase as the main limitation in carotenoid biosynthesis in Yarrowia lipolytica. To overcome this bottleneck, we exploit two independent approaches. Structure-guided protein engineering yields a variant, Y27R, characterized by complete loss of substrate inhibition without reduction of enzymatic activity. Alternatively, establishing a geranylgeranyl pyrophosphate synthase-mediated flux flow restrictor also prevents the onset of substrate inhibition by diverting metabolic flux away from the inhibitory metabolite while maintaining sufficient flux towards product formation. Both approaches result in high levels of near-exclusive ß-carotene production. Ultimately, we construct strains capable of producing 39.5 g/L ß-carotene at a productivity of 0.165 g/L/h in bioreactor fermentations (a 1441-fold improvement over the initial strain). Our findings provide effective approaches for removing substrate inhibition in engineering pathways for efficient synthesis of natural products.

The structural and functional characteristics of soluble dietary fibers modified from tomato pomace with increased content of lycopene.

The tomato pomace, a by-product of tomato processing, was rich in nutrients such as lycopene (Lyc), vitamins, phenols and soluble dietary fibers (SDF). Homogenization combined with enzymatic hydrolysis (HE) was firstly applied to obtain HE-pomace. The yield of Lyc was raised by 57.2% after HE treatment by the optimal condition. The extraction rate of HE-SDF was increased by 73.4%. In order to clarify the relationship between the SDF and the release of Lyc, SDFs were characterized by structural analysis and morphological determination. The results suggested that HE-SDF possessed smaller molecular weight and loose microstructure with shorter chains. It implied that the degradation of dietary fiber led to the release of Lyc molecules. Besides, HE-SDF exhibited stronger capacity of water-holding, glucose adsorption and bile acid binding. In conclusion, HE treatment possessed the potential to be applied as an excellent modification method, which improved the nutritional and economic value of tomato pomace.

Red Tomato Products as an Alternative to Reduce Synthetic Dyes in the Food Industry: A Review.

Most dyes used in the food industry are synthetic and can be a health hazard. Red tomato may serve as a natural alternative dye to replace synthetic colorants. This study aimed to review the literature on the addition of red tomato products (powder tomato, paste, freeze-dried, tomato peel powder, tomato pomace) to reduce the usage of synthetic dyes in the food industry. Red tomato products have been used as coloring in pasta, bologna, sausages, cookies, crackers, macaroons, hamburgers, breads, muffins, cheeses, and nuggets. The trans-cis isomerization of lycopene by oxidative processes directly affects the color of the pigment. The lycopene contained in tomato has antioxidant activity and could reduce or eliminate other oxidants and/or synthetic preservatives in food. Moreover, tomatoes in foods have high sensory scores, nutritional appeal, and marketing potential. However, its use as a food colorant has been not extensively explored. Therefore, further studies are still required, especially on the stability of carotenoids in tomatoes used in processed foods.

Multifaceted Effects of Lycopene: A Boulevard to the Multitarget-Based Treatment for Cancer.

Lycopene is a pigment belonging to the group of carotenoids and it is among the most carefully studied antioxidants found especially in fruit and vegetables. As a carotenoid, lycopene exerts beneficial effects on human health by protecting lipids, proteins, and DNA from damage by oxidation. Lycopene is a powerful oxygen inactivator in the singlet state. This is suggestive of the fact that lycopene harbors comparatively stronger antioxidant properties over other carotenoids normally present in plasma. Lycopene is also reported to hinder cancer cell proliferation. The uncontrolled, rapid division of cells is a characteristic of the metabolism of cancer cells. Evidently, lycopene causes a delay in the progression of the cell cycle, which explains its antitumor activity. Furthermore, lycopene can block cell transformation by reducing the loss of contact inhibition of cancer cells. This paper collects recent studies of scientific evidence that show the multiple beneficial properties of lycopene, which acts with different molecular and cellular mechanisms.

Acetylated cashew gum and fucan for incorporation of lycopene rich extract from red guava (Psidium guajava L.) in nanostructured systems: Antioxidant and antitumor capacity.

Industrial application of lycopene is limited due to its chemical instability and low bioavailability. This study proposes the development of fucan-coated acetylated cashew gum nanoparticles (NFGa) and acetylated cashew gum nanoparticles (NGa) for incorporation of the lycopene-rich extract from red guava (LEG). Size, polydispersity, zeta potential, nanoparticles concentration, encapsulation efficiency, transmission electron microscopy (TEM) and atomic force microscopy (AFM) were used to characterize nanoparticles. The antioxidant activity was determinated and cell viability was evaluated in the human breast cancer cells (MCF-7) and human keratinocytes (HaCaT) by MTT assay. The toxic effect was evaluated by hemolysis test and by Galleria mellonella model. NFGa showed higher stability than NGa, having a size of 162.10 ± 3.21 nm, polydispersity of 0.348 ± 0.019, zeta potential -30.70 ± 0.53 mV, concentration of 6.4 × 109 nanoparticles/mL and 60% LEG encapsulation. Microscopic analysis revealed a spherical and smooth shape of NFGa. NFGa showed antioxidant capacity by ABTS method and ORAC assay. The NFGa presented significant cytotoxicity against MCF-7 from the lowest concentration tested (6.25-200 µg/mL) and did not affect the cell viability of the HaCaT. NFGa showed non-toxic effect in the in vitro and in vivo models. Therefore, NFGa may have a promising application in LEG stabilization for antioxidant and antitumor purposes.

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.

pH-Dependent complexation between ß-lactoglobulin and lycopene: Multi-spectroscopy, molecular docking and dynamic simulation study.

This study aims to investigate the effect of pH levels (pH 7.0 and pH 8.1) on binding ability of ß-lactoglobulin (ß-LG) with lycopene (LYC) and elucidate interaction mechanisms using multi-spectroscopy and molecular docking study. ß-LG at pH 8.1 showed a stronger binding affinity to lycopene than that at pH 7.0 according to binding constant, binding number, energy transfer efficiency, and surface hydrophobicity. Lycopene bound to protein mainly by van der Waals force in the form of static quenching mode and preferred to interact with ß-LG at the top of barrel for both pH levels. Molecular dynamic simulation revealed that ß-LG/LYC complex at pH 8.1 was more stable than at pH 7.0. ß-LG/LYC complexes formed at pH 8.1 showed significantly higher ABTS radical scavenging activity than samples at pH 7.0 (p < 0.05). Data obtained may contribute valuable information for preparing a whey protein-based delivery system for lycopene.

Photogeneration of Long-Lived Triplet States through Singlet Fission in Lycopene H-Aggregates.

Molecular triplet excitons produced through singlet fission (SF) usually have shorter triplet lifetimes due to exciton-exciton recombination and relaxation pathways, thereby resulting in complex device architectures for SF-boosted solar cells. Using broadband transient absorption spectroscopy, we here show that the photoexcitation of nanostructured lycopene H-aggregates at room temperature produces free triplets with an unprecedented 35-fold enhancement in the lifetime compared to those localized on the monomer backbone. The observed rise of a spectrally blue-shifted correlated T-T pair state in ∼19 ps with distinct vibronic features provides the basis for SF-induced triplet generation.

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.

Tomato and lycopene and multiple health outcomes: Umbrella review.

Lycopene is a potent lipophilic antioxidant in tomato. We aim to clarify the evidence for associations between tomato and lycopene and multiple health outcomes. Umbrella review of meta-analyses and systematic reviews was performed in humans. A total of 174 articles were searched, 17 articles with 20 health outcomes were identified by eligibility criteria. Tomato intake was inversely associated with all-cause mortality, coronary heart disease mortality, cerebrovascular disease mortality, prostate cancer, and gastric cancer. Dietary lycopene intake or serum lycopene was inversely associated with all-cause mortality, prostate cancer, stroke, cardiovascular disease, metabolic syndrome, and male infertility. Caution was warranted for potential allergy and pollution. The quality of the vast majority of evidence by GRADE was low or very low with the remaining six as moderate. The intake of tomato or lycopene was generally safe and beneficial for multiple health outcomes in humans. But the quality of the evidence was not high.

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.

Development of a Highly Water-Soluble Lycopene Cyclodextrin Ternary Formulation by the Integrated Experimental and Modeling Techniques.

Lycopene, the aliphatic hydrocarbon carotenoid with abundant bioactivities, has instability, extremely poor water solubility, and low oral bioavailability. The study aimed to develop a highly water-soluble and practical lycopene formulation to improve the oral bioavailability and efficiency of lycopene. Environment-friendly hot-melt extrusion (HME) technique was applied to fabricate lycopene-cyclodextrin-polyethylene glycol 6000 (PEG 6000) ternary systems, which possessed highly aqueous solubility (897.665 µg mL-1), almost 32-fold higher than that of the reported lycopene binary inclusion (27.1 ± 3.2 µg mL-1). The dissolution rate was significantly accelerated compared to pure lycopene. The molecular mechanism was further investigated by the integrated experimental and modeling tools. Molecular dynamics (MD) simulation revealed lycopene molecule was wrapped within the aggregates of hydroxypropyl-beta-cyclodextrin (HP-ß-CD) and PEG 6000 through extensive hydrogen bond interactions, which was experimentally validated by DSC, XRD, and FTIR spectrum analysis. The third component PEG 6000 facilitated the process of HME and augmented hydrogen bond interactions with HP-ß-CD. Moreover, lycopene inclusions exhibited significant antitumor activity via inhibiting cell proliferation and inducing apoptosis. The pharmacokinetic studies showed the relative bioavailability of lycopene ternary preparation was up to 313.08% and the Cmax was 4.9-fold higher than that of the marketed tablet. In conclusion, the lycopene cyclodextrin ternary formulation developed by the modified HME techniques is suitable for industrial production, while PEG 6000 plays a vital part in the multicomponent systems to increase solubility, dissolution rate, and oral bioavailability of lycopene. The combination of experimental and computational tools is able to benefit the development of multicomponent formulations accurately and effectively.

Biological Activities of Z-Lycopenes Contained in Food.

Mono-(5Z)-, -(9Z)-, and -(13Z)-lycopenes are found in food containing processed tomato products, while tetra-Z-(7Z, 9Z, 7'Z, 9'Z)-lycopene (prolycopene) is found in tangerine-strain tomatoes. We prepared pure mono-Z-lycopenes from all-E-lycopene via chemical reaction (heating in CH2Cl2 at 80℃ for 1 h) followed by purification using preparative silica gel HPLC, while prolycopene was isolated from tangerine tomatoes by partitioning with n-hexane and 90% MeOH followed by silica gel column chromatography. A simple method of distinguishing the mono-Z-lycopenes using the 13C NMR chemical shifts of their Z-methyl carbons is proposed. Additionally, the 1O2 quenching and 3T3-L1 cell differentiation activities of the compounds were then compared with all-E-lycopene for the first time. All the evaluated Z-isomers showed 1O2 quenching activities that were equal to or slightly lower than that of all-E-lycopene, with the IC50 values for the 1O2 quenching activities of (all-E)-, (5Z)-, (9Z)-, (13Z)-, and (7Z, 9Z, 7'Z, 9'Z)-lycopene being 4.4±0.36, 4.0±1.44, 5.3±1.08, 6.9±1.67, and 8.7±0.34 µM, respectively. The mouse 3T3-L1 cell differentiation activities followed the order: (all-E) > (9Z) > (5Z) ≈ (9Z) ≈ (13Z) ≈ (7Z, 9Z, 7'Z, 9'Z).

Biotechnological Advances in Lycopene ß-Cyclases.

Lycopene ß-cyclase is one of the key enzymes in the biosynthesis of carotenoids, which catalyzes the ß-cyclization of both ends of lycopene to produce ß-carotene. Lycopene ß-cyclases are found in a wide range of sources, mainly plants and microorganisms. Lycopene ß-cyclases have been extensively studied for their important catalytic activity, including for use in genetic engineering to modify plants and microorganisms, as a blocking target for lycopene industrial production strains, and for their genetic and physiological effects related to microorganic and plant biological traits. This review of lycopene ß-cyclases summarizes the major studies on their basic classification, functional activity, metabolic engineering, and plant science.