Selected Methods of Extracting Carotenoids, Characterization, and

Review pubs.acs.org/JAFC

Cite This: J. Agric. Food Chem. 2018, 66, 5925−5947

Selected Methods of Extracting Carotenoids, Characterization, and Health Concerns: A Review Parise Adadi,* Nadezhda Vasilyevna Barakova, and Elena Fedorovna Krivoshapkina

Downloaded via UNIV OF TOLEDO on June 29, 2018 at 13:29:13 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

ITMO University, Lomonosova Street 9, 191002, St. Petersburg, Russia Federation ABSTRACT: Carotenoids are the most powerful nutrients (medicine) on earth due to their potent antioxidant properties. The ability of these tetraterpenoids in obviating human chronic ailments like cancer, cardiovascular disease, osteoporosis, and diabetes has drawn public attention toward these novel compounds. Conventionally, carotenoids have been extracted from plant materials and agro-industrial byproduct using different solvents, but these procedures result in contaminating the target compound (carotenoids) with extraction solvents. Furthermore, some utilized solvents are not safe and hence are harmful to the environment. This has attracted criticism from consumers, ecologists, environmentalists, and public health workers. However, there is clear consumer preference for carotenoids from natural origin without traces of extracting solvent. Therefore, this review seeks to discuss methods for higher recovery of pure carotenoids without contamination from a solvent. Methods such as enzyme-based extraction, supercritical fluid extraction, microwave-assisted extraction, Soxhlet extraction, ultrasonic extraction, and postextraction treatment (saponification) are discussed. Merits and demerits of these methods along with health concerns during intake of carotenoids were also considered. KEYWORDS: antioxidant, cancer, α- and β-carotenes, functional food, plant materials

1. INTRODUCTION According to ref 1, carotenoids are a class of pigmented compounds that are synthesized in plants and microorganisms but not animals. They are responsible for photosynthetic mechanisms and protecting plants against photodamage. The chemical structure of carotenoids is composed of a polyene skeleton which usually consists of 40 carbon atoms and is either acyclic or terminated by one or two cyclic end groups.2 The colors of these pigments range from yellow to red and are found in tomatoes (lycopene Figure 1B), maize corn (zeaxanthin), and carrots (β-carotene).3 This group of valuable molecules are of interest to food and feed companies as well as chemical and pharmaceutical firms because of not only their capability as a vitamin A precursor but also their antioxidant, color, and antitumor activities.4 The potential role of carotenoids in averting prostate cancer and cardiovascular diseases in humans has recently gained attention globally. Owing to its antioxidant potency, it possesses the ability to act as a free radical scavenger. In biological systems, lycopene has the highest singlet oxygen-quenching rate among all the carotenoids.5−10 Carotenoids are used in cosmetic products (pomades) due to their photoprotection abilities against ultraviolet (UV) radiation. Keratinocytes (an epidermal cell which generates keratin to serves as a barrier) present in the epidermis of skin absorbs UV-B radiations (280−315 nm) and UV-A radiation (320−400 nm) which can lead to the development of erythema and UV-carcinogenesis, respectively.11 According to ref 12, researchers face challenges during extraction of these valuable compounds due to oxidation, losses, and time. Much time is wasted during incubation periods, for instance,13 using benzene and boiling methanol to wash crystals 10 times, which is time-consuming and not practical on an industrial scale of extraction. Conventionally, © 2018 American Chemical Society

carotenoids have been extracted from fruits and vegetables using different solvents, but in general, these procedures result in contaminating the extraction solvents. However, there is a clear consumer preference for carotenoids without traces of extracting solvent. For this reason, a great amount of resources (particularly huge sums of money) have been allocated for scientific research on the extraction of bioactive compounds for the development of these functional foods. The most potent antioxidant among all carotenoids is lycopene which is widely used in healthcare products, food, and cosmetics.14 With a huge population of low-income earners in most African countries, a large portion of the people cannot afford a daily balanced diet coupled with the fact that fruit consumption after a meal is not widely practiced among the people; hence, exposure to diseases which could be prevented by carotenoids becomes pronounced. Nutraceutical supplements of these carotenoids are already in the market for purchase. For example, FloraGLO-lutein, Cathatene 10% FT (fluid type), Lycotone-XX, and Alpha GPC capsules can be purchased and taken as a supplement or as food additives, i.e., adding to beverages. For these reasons, much research has sprung up with the scientific interest of investigating for alternate methods of extraction, different from the conventional solvent extractions. Therefore, enzyme-based extraction, supercritical fluid extraction, microwave-assisted extraction, Soxhlet extraction, and ultrasonic extraction are considered in this review as real options for carotenoid extraction. Furthermore, the classifications, type, and biosynthesis of carotenoids are discussed. Received: Revised: Accepted: Published: 5925

March 19, 2018 May 31, 2018 May 31, 2018 May 31, 2018 DOI: 10.1021/acs.jafc.8b01407 J. Agric. Food Chem. 2018, 66, 5925−5947

Review

Journal of Agricultural and Food Chemistry

Figure 1. Molecular structures of various carotenoids: (A) Canthaxanthin, (B) Lycopene, (C) Astaxanthin, (D) Lutein.

yolk.29−31 Sea buckthorn (Hippophae rhamnoides) was found to contain β-carotene, lycopene, and zeaxanthin. Moreover, oils from seed, fruit pulp (juice), and fruit residue of H. rhamnoides after removing juice is thought to also contain carotenoids in ranges of 30−250, 300−850, and 1280−1860 mg/g, respectively.32 Sommerburg et al.33 reported that orange pepper and wolfberry were rich in zeaxanthin. Spinach, celery (stalks and leaves), brussels sprouts and scallions, broccoli, and lettuce (green) were found to be good sources of lutein with varying quantities of 47%, 34%, 27%, 22%, and 15% respectively. According to ref 34, the skin pigmentation of birds, egg yolk, pigs, and some fishes (salmon) are imparted by zeaxanthin. The red hues in vegetables (tomatoes and its products, i.e., tomato sauce, tomato soup, and tomato juice) and fruits (watermelon, Gac) are the results of lycopene. Other sources include papaya, guava, apricot, autumn olive,35 Japanese persimmon,36 pitanga ripe fruit,37 red cabbage,38 carrot, red roots,39,40 and bitter melon.41 Tomatoes contain about 3.1 mg per 100 g of lycopene.31 A recent published paper42 revealed that dehydrating plant matrixes gave a higher yield of lycopene. Fresh and freeze-dried matrices of gac, tomato, and watermelon contains 1.34 ± 0.19, 0.22 ± 0.03, and 0.05 ± 0.01 and 4.5 ± 0.2, 10.6 ± 0.4, and 2.2 ± 0.1 (g/kg f-DW) of lycopene, respectively. Nevertheless, the freeze-dried matrices contain a 3-, 40-, and 82-fold greater total lipid content compared to the fresh plant materials, respectively. Neoxanthin and violaxanthin (xanthophyll epoxy-carotenoids) are predominant in potherbs. The major sources include leek (1.0 mg/100 mg), arugula (1.0 mg/100 g), lamb’s lettuce (0.9 mg/100 g), yellow bell peppers (4.4 mg/100 g), spinach

2. SOURCES OF CAROTENOIDS 2.1. Plant. Dark green vegetables, colored fruits, and flowers are the main sources of natural carotenoids.15 Food sources and the quantity of carotenoids present are shown in Table 1. According to refs 18 and 19, β-carotene, α-carotene, βcryptoxanthin, lycopene, lutein, zeaxanthin, neoxanthin, canthaxanthin, and capsanthin are the major carotenoids which can be extracted from fruits and vegetables due to the yelloworange pigments. Carrots, cantaloupe, spinach, lettuce, tomatoes, sweet potatoes, and broccoli are rich sources of βcarotene. Canola and golden rice are excellent sources as well. Some fruits and vegetables can serve as sources of both α- and β-carotenes. Ripening and conditions during processing affect the content of carotenoids; i.e., the ratio of β-carotene and β-cryptoxanthin can be altered.20,21 From previous studies,22−24 it was discovered the bioavailability of β-carotene would be improved drastically in the presence of dietary fat. β-Cryptoxanthin occurs predominately in Citrus unshiu MARC;25,26 however, fruits such as peach, papaya, orange, and tangerine also contain some amount.27 Persimmon (Diospyros kaki), squash/pumpkin (Cucurbita spp), pepper (red, orange) (C. annuum), and loquat (Eriobotrya japonica) are other sources of β-cryptoxanthin.28 Green leafy vegetables are a rich source for lutein and zeaxanthin. However, these yellow pigments are also in produce such as zucchini, spinach, broccoli, squash, kiwi fruit, grapes, orange juice, yellow capsicums, persimmons, tangerines, and mandarins. The highest concentrations of lutein and zeaxanthin are present in maize (60% of the total carotenoids) and egg 5926

DOI: 10.1021/acs.jafc.8b01407 J. Agric. Food Chem. 2018, 66, 5925−5947

Review

Journal of Agricultural and Food Chemistry Table 1. Carotenoids Content in Major Planta Sources Carrot (raw) Carrot (cooked) Pumpkin Winter Squash (Butternut) Plantains (raw) Banana (raw) Balsam-pear (raw) Carrot (raw) Carrot (cooked) Mango Mango canned Sweet potato cooked Pumpkin canned Peppers (raw) Pepper (cooked) Okra Apricots Asparagus Tomato (raw) Tomato (cooked) Tomato paste Tomato sauce Tomato soup Tomato juice Watermelon Papaya Pink grapefruit Pink guava Gac Mandarin oranges Tangerine Papaya Orange juice

Carotenoids α-carotene

β-carotene

Lycopene

β-Cryptoxanthin

Quantity-wet weight based (mg/100g)

Sources Spinach Broccoli Lettuce Green peas Watercress Maize Mandarin oranges Red pepper Yellow bell pepper Spinach Creamed spinach Beko (Oroxylum indicum) Beluntas (Pluchea indica) Cekur manis (Sauropus androgynu) Mengkudu (Morinda citrifolia) Paraga (Centella asiatica) Arugula Leek Lamb’s lettuce Paraga (Centella asiatica) Mengkudu (Morinda citrifolia) Cekur manis (Sauropus androgynu)

5.00 3.70 2.72 1.13 0.72 0.29 2.18 18.30 8.00 2.15 13.10 9.50 6.90 2.40 2.20 0.18 3.82 1.19 3.00 4.40 29.30 15.90 10.90 9.30 4.90 3.40 0.03 0.05 2−3 1.77 1.60 0.47 1.98

Carotenoids Lutein

Zeaxanthin

Violaxanthin

Quantity-wet weight based (mg/100g) 6.26 2.26 1.25 1.84 10.71 0.44 0.14 0.60 4.40 2.80 2.50 0.10 0.06 0.12 0.03

Neoxanthin

0.08 1.00 1.00 0.90 0.03 0.13 0.09

a Modified with permission from Stephen N. M. et al. Carotenoids: Types, Sources, and Biosynthesis in Plant Secondary Metabolites: Volume 2: Stimulation, Extraction, and Utilization; Siddiqui, M. W., Bansal, V., and Prasad, K., Eds. Copyright 2016 Apple Academic Press. http://www.appleacademicpress.com/plant-secondarymetabolitesvolume-2-stimulation-extraction-and-utilization/ 9781771883542.16,17

food and pharmaceutical industries. Algae are considered to be a rich source of other bioactive molecules which have a positive impact on human health.49,50 Alloxanthin, crocoxanthin, and monaxanthin (known as acetylenic carotenoids) are synthesized in some divisions while β-carotene and zeaxanthin are found in all the classes of algae. The strains Chlorococcales can produce carotenoids that include astaxanthin, echinenone, ketocarotenoids, and canthaxanthin.51,52 Del Campo et al.53 and Hagen et al.54 reported that Haematococcus pluvialis, Chlorococcum sp., Chlorella zof ingiensis, and Chlorella vulgaris (chlorophyte) synthesized predominantly astaxanthin and its derivatives. Zeaxanthin is found in both red (Porphyridium cruentum and Gracilaria Damaecornis) and brown algae (Macrocystis pyrifera) although they are predominant in species such as Nannochloropsis oculata, Chaetoceros gracilis, and Dunaliella salina.55−57 Red (Eucheuma isiforme etc.) and green (Chlorophyta) algal species are the major sources of lutein.52,56 Chlorophyta produced mainly violaxanthin and neoxanthin whereas Heterokontophyta, Haptophyta, Dinophyta, and Euglenophyta are the major source of diatoxanthin.58,52 According to refs 59 and 60, fucoxanthin can be extracted from brown algae (Sargassum binderi, Sargassum duplicatum, and Undaria pinnatif ida). Production of carotenoids by algae is directly influenced by certain conditions such as stress (alkaline pH, dark conditions), size of the inoculum, intensity of light,

(2.8 mg/100 g), and creamed spinach (2.5 mg/100 g) for Neoxanthin and violaxanthin, respectively.31 As cited in ref 43, angiosperms also contain a significant quota of neoxanthin and violaxanthin with Canna indica making 8% of the carotenoids. Fatimah et al.17 detected the highest amount of neoxanthin (235.36 ± 11.02 μg/g DW) and violaxanthin (83.98 ± 6.86 μg/g DW) in mengkudu and pegaga, respectively. Mushroom, Capsicum annum, and saffron plant are the main sources of canthaxanthin, capsanthin, capsorubin, crocin, and crocetin.44 Marine algae and crustaceans aside mushroom were also identified to contain canthaxanthin.45 Crocus sativus L. produces carotenoids such as crocin and crocetin which are mainly utilized as a colorant in the food industries.46 Moreover, Capsanthin is also used as a food colorant present in sweet and chili peppers.31 2.2. Microbial Sources. Microbial production of carotenoids allows for a more sustainable and environmentally friendly approach than some of the conventional chemical methods of extraction. Algae, fungi, bacteria, marine organisms (photosynthetic organisms), and vertebrates synthesize a wide variety of carotenoids44,47,48 (Table 2). 2.2.1. Algae and Marine Organism (Grasses and Animals). Specific functions and unique structure of carotenoids extracted from algae and other marine organisms are of interest in the 5927


5928

Cryptoxanthin Adonirubin, adonixanthin α- and β-bacterioruberin

Canthaxanthin

Echinenone, phoenicoxanthin Myxol Mytiloxanthin Caloxanthin Nostoxanthin

Siphonaxanthin Loroxanthin Antheraxanthin Alloxanthin Torulene and torularhodin Neurosporoxanthin

Neoxanthin Diatoxanthin Fucoxanthin

Lycopene Vialoxanthin

Lutein

α-Carotene Zeaxanthin

Haloferax alexandrines, Thraustochytrid strain KH10, Dietzia natronolimnaea HS-1

tunicates, mussels and oysters

Gonads of sea urchin

Muriellopsis sp., Chlorella protothecoides, Eucheuma isiforme, Chlorella zof ingiensis, Coccomyxa acidophila, Scenedesmus almeriensis, Botryococcus braunii, dolphin Haloarchaea Chlorophyta, Botryococcus braunii, Gracilaria birdiae, Posidonia oceanica, Cymodocea nodosa, Zostera noltii, Halophila stipulacea Chlorophyta, Posidonia oceanica, Cymodocea nodosa, Zostera noltii, Halophila stipulacea Heterokontophyta, Haptophyta, Dinophyta, Euglenophyta. Undari pinnatif ida, Heterokontophyta, Sargassum binderi, Sargassum duplicantum, Odontella aurita, Phaeodactylum tricornutum, Isochrysis af f. Galbana, Laminalia japonica, Hijikia f usiformis, Undaria pinnatif ida, Laminaria japonica, Alaria crassifolia, Cladosiphon okamuranus, Cystoseira hakodatensis, Eisenia bicyclis, Hijikia f usiformis, Ishige okamurae, Kjellmaniella crassifolia, Myagropsis myagroides, Padina tetrastromatica, Petalonia binghamiae Codium f ragile Euglenophyta, Chlorarachniophyta, Chlorophyta Gracilaria birdiae, Posidonia oceanica, Cymodocea nodosa, Zostera noltii, Halophila stipulacea Gracilaria birdiae

Nannochloropsis oculata, Chaetoceros gracilis, Dunaliella salina, Porphyridium cruentum, Gracilaria damaecornis, Macrocystis pyrifera, Botryococcus braunii, Gracilaria birdiae

Botryococcus braunii, Dunaliella salina, Gracilaria birdiae, Posidonia oceanica, Cymodocea nodosa, Zostera noltii, Halophila stipulacea, shellfish, sea urchin, starfish, holoturians, dolphin

β-Carotene

Rhodotorula minuta, Rhodosporidium sp., Verticillium agaricinum, Sporobolomyces roseus Neurospora crassa, Fusarium sp., Verticillium sp., Podospora anserine, Giberella fujikuroi, Phycomyces blakesleanus Phaf f ia rhodozyma

Blakeslea trispora

Blakeslea trispora, Phycomycus blakesleeanus, Choanephora cucurbitarum, Rhodotorula aurea, Rhodosporidium diobovatum, Aspergillus giganteus, Sporobolomyces roseus Rhodotobacter sphaeroides, Rhodotorula glutinis Rhodotorula acheniorum Rhodotorula mucilaginosa,

Fungi/yeast Xanthophyllomyces dendrorhous, Peniophora sp., Phaf f ia rhodozyma, Thraustochytrium strains ONC-T18 and CHN-1, Thraustochytriidae sp. AS4-A1, Aurantiochytrium sp. KH105

Algae, seagrasses, and marine animals

Haematococcus pulvialis, Chlorococcum sp., Chlorella zof ingiensis, Chlorella vulgaris, Botryococcus braunii, Thraustochytrid strain KH105, Arbacia lixula, Charonia sauliae, starfish, holoturians, crabs, shrimp, lobsters, shellfish, Whales

Carotenoids

Astaxanthin

Table 2. Microbial Sources of Carotenoidsa

Synechococcus sp.

Synechococcus sp. Synechococcus sp., Thermosynechococcus elongatus

Synechococcus sp., Thermosynechococcus elongates, Prochlorococcus marinus, Trichodesmium sp., Calothrix elenkenii, Synechocystis sp., Lyngbya sp. Prochlorococcus marinus Synechococcus sp., Thermosynechococcus elongates

Cyanobacteria

Bacteria

Paracoccus sp. strain DSM 11574 Halobacterium salinarium, Halobacterium sarcina

Bradyrhizobium sp., Paracoccus sp. strain DSM 11574

Erythobacter sp.

Paracoccus sp. strain DSM 11574 Flavobacteriaceae

Flavobacterium sp., Paracoccus zeaanthinifaciens

Agrobacterium aurantiacum, Paracoccus Carotinifaciens, Paracoccus sp. strain DSM 11574. Enterobacter sp. strain P41 Paracoccus sp. strain DSM 11574

Journal of Agricultural and Food Chemistry Review


Review

Sarcinaxanthin β-cryptoxanthin

sea squirt and sea pineapple (e.g., Halocynthia roretzi), Paracentrotus lividus

Heterocapsa triquetra, Symbiodinium, Anemonia sulcate, Amaroucium pliciferum

and the concentration of inorganic phosphates.31 Gracilaria birdiae is observed to produce antheraxanthin and alloxanthin while euglenophyta, chlorarachniophyta, chlorophyta, and codium fragile synthesized Loroxanthin and siphonaxanthin, respectively.52,61,62 According to ref 63, seagrasses are plants which are capable of flourishing along the coastlines (in both temperate and tropical conditions) of the world. This helps in balancing the marine ecosystem and biodiversity. The photosynthetic ability of the marine grasses is similar to that of terrestrial plants because of the different light exposure at variable depth hence constituting carotenoids of different quantities and quality.64,65 Casazza and Mazzella65 extracted six different kinds of carotenoids (lutein, zeaxanthin, violaxanthin, neoxanthin, and siphonaxanthin) from Mediterranean seagrass species, Posidonia oceanica, Cymodocea nodosa, Zostera noltii, and Halophila stipulacea. In another study, it was discovered that leaves of Cymodocea nodosa and Zostera marina contain seven photosynthetic carotenoids.66 Galasso et al.48 listed sponges, anemones, corals, jellyfishes, and ascidians among marine invertebrates exhibiting wide ranges of hues due to various carotenoids they contain. This could be as a result of metabolic transformations or from the feed they depend on because naturally they do not synthesize carotenoid de novo.67 Carotenoids present in sponges make them brilliantly colorful.68 Aryl carotenoids (isorenieratene, renieratene, and renierapurpurin) are predominant in sponges.69 Some corals and jellyfish were found to contain peridinin, pyrrhoxanthin, diadinoxanthin, and astaxanthin, respectively.68,70 Bivalves (oyster, clam, scallop, mussel, ark shell, etc.), sea slugs, sea snails, and sea hare contain lutein, zeaxanthin, fucoxanthin, apocarotenoids, diatoxanthin, diadinoxanthin, alloxanthin, etc. which originate from the food (microalgae) they consume. Some of these animals are carnivores.71−74 As stated in refs 73, 75, and 76, phytoplankton are the major sources of carotenoid for protochordata (tunicates) which includes ascidians. However, they can also originate as metabolites of fucoxanthin, diatoxanthin, and alloxanthin biosynthesis. Marine animals show a structural diversity of carotenoids such as β-carotene, fucoxanthin, peridinin, diatoxanthin, alloxanthin, and astaxanthin. These carotenoids are known to accumulate from the feed (algae and other animals) these organisms consume. Through biotransformation, the marine organisms could modify the various carotenoid in a series of pathways. Whales feed on krill and hence could accumulate astaxanthin. Octopus and cuttlefish were also found to be a major source of astaxanthin. It is revealed that dolphin is a source of β-carotene and lutein.68,77,78 Moreover, salmonid fish and perciformes also accumulate the esterified form of carotenoids in their tegument and gonads and lack the necessary enzymes to synthesis astaxanthin from other carotenoids but depend on crustacean zooplankton as the sole source. The bright yellow hues in the fins and skin of perciformes are a result of tunaxanthin.48,69 For extensive review about carotenoids in marine animals, refer to refs 47, 72, 74, 75, 79, and 80. 2.2.2. Fungi. According to ref 81, fungi and yeast such as Mucorales (Mucoromycotina), Blakeslea trispora, Phycomycus blakesleeanus, Choanephora cucurbitarum, and Rhodotorula aurea are predominant sources of carotenoids. Industrial production of food colorant (β-carotene) is mainly employed by B. trispora.

a Modified with permission from Stephen N. M. et al. Carotenoids: Types, Sources, and Biosynthesis in Plant Secondary Metabolites: Volume 2: Stimulation, Extraction, and Utilization; Siddiqui, M. W., Bansal, V., and Prasad, K., Eds. Copyright 2016 Apple Academic Press. http://www.appleacademicpress.com/plant-secondary-metabolites-volume-2-stimulation-extraction-and-utilization/ 9781771883542,48

Deinococcus radiodurans Micrococcus luteus Paracoccus sp. strain DSM 11574

Thermus thermophilus

Halocynthiaxanthin and Fuxoxanthinol Deinoxanthin

Carotenoids

Staphyloxanthin Peridinin Thermozeaxanthin

Table 2. continued

Algae, seagrasses, and marine animals

Fungi/yeast

Cyanobacteria

Bacteria

Staphylococcus aureus


5929


Review


in a significant increase in yield of β-carotene. Moreover, aerobic conditions also favor the formation of β-carotene when Lyngbya sp. and Synechocystis sp. were cultured. Irradiation or gene deletion altered the synthesis of canthaxanthin and βcarotene. Synechocystis sp. was also found to produce zeaxanthin.31,106,110 2.2.4. Bacteria. Nonphotosynthetic and nonphotosynthetic bacteria are found to produce major carotenoids (details discussed in refs 111 and 112). Carotenoids such as β-carotene, lycopene, canthaxanthin, zeaxanthin, astaxanthin, α-bacterioruberin, β-bacterioruberin, deinoxanthin, thermozeaxanthins, nostoxanthin, caloxanthin, sarcinaxanthin, and staphyloxanthin are found to be synthesized by numerous bacteria which have gained considerable attention due to the sustainability, natural products, and potential cost-effectiveness of this method. Microbial production is widely accepted by consumers113−124 unlike the chemical method of synthesis which has attracted criticism. Metabolic engineering has been utilized to developed novel Escherichia coli for producing carotenoid via fermentation. These strains produce a significant amount of carotenoids (i.e., lycopene, β-carotene, zeaxanthin, and astaxanthin).108,117,125−132 According to ref 133, a species of Paracoccus was discovered to produce β-carotene, echinenone, β-cryptoxanthin, canthaxanthin, astaxanthin, zeaxanthin, adonirubin, and adonixanthin. Systems of metabolic engineering have been applied to stimulate a precursor compound (isopentenyl diphosphate (IPP)) of carotenoid biosynthesis in E. coli of an endogenous 2C-methyl-D-erythritol 4-phosphate (MEP) pathway or mevalonate (MVA) pathway. Among five recombinant E. coli strains (MG1655, DH5α, S17-1, XL1-Blue, and BL21) that were compared, DH5α was found to produce 465 mg/L of βcarotene. Caloxanthin, zeaxanthin, and nostoxanthin were synthesized when CrtE, CrtB, CrtI, CrtY, CrtZ, CrtX, from P. ananatis and CrtG from Brevundimonas SD212 were inserted into E. coli.123,134 According to refs 135 and 136 high titers of zeaxanthin were synthesized by Flavobacterium sp. and Paracoccus zeaanthinifaciens. Bradyrhizobium sp., Agrobacterium aurantiacum, and Paracoccus carotinifaciens were found to accumulate high amounts of canthaxanthin and astaxanthin. Asker et al.137 reported the pleomorphic bacterial strain (TDMA-16T) as a producer of zeaxanthin and nostoxanthin. Enterobacter species P41 and halobacteria (Halobacterium salinarium and HalobacteriumSarcina) were observed to produce a significant amount of β-carotene and α-, βbacterioruberin, respectively.113,138 Lactobacillus plantarum strain CECT7531 and Staphylococcus aureus were identified to produce carotenoids such as 4,4′-diaponeurosporene and staphyloxanthin. S. aureus is immune to oxidative stress because of staphyloxanthin. Moreover, since staphyloxanthin is a membrane-bound carotenoid, it protects lipids but might also be involved in protecting proteins and DNA.139−141 Thermozeaxanthin, a rare carotenoid, was extracted from Thermus thermophiles, whereas nostoxanthin and sarcinaxanthin were found to be synthesized by Erythobacter sp. and Micrococcus luteus respectively.142−144 2.3. Type of Carotenoids. Carotenoids can be divided into three main categories, mainly based on the presence or absence of oxygen (lutein (Figure 1D), violaxanthin, zeaxanthin, and αcryptoxanthin), chemical structure, and others (apocarotenoids, homocarotenoids, secocarotenoids, norcarotenoids) (Figure 2).31 Other classes of carotenoids are listed in Table 3.

Finkelstein et al.82 patented their finding of how the yield of βcarotene is doubled when they employed B. trispora. βCarotene, γ-carotene, torulene, and torularhodin are predominant carotenoids found in species of Rhodotorula and Rhodosporidium.83 Lycopene can be synthesized by B. trispora by altering some media conditions (pH and concentration of salts and some amines) to impede proteins responsible for cyclization of lycopene to β-carotene.84 An ultrasonic treatment of B. trispora resulted in the production of 173 and 82 mg/L of β-carotene and lycopene, respectively.85 An increase in yield was observed in β-carotene from 44% to 65% and lycopene from 51% to 78% when n-hexane and n-dodecane were incorporated in the media. The addition of antibiotics, natural oils, amino acids, and vitamin A in culture media of B. trispora resulted in a significant increase in yield of β-carotene.86,87 Xanthophyllomyces dendrorhous and Phaf f ia rhodozyma are predominant producers of astaxanthin. However, X. dendrorhous is utilized for large-scale production of astaxanthin.88−95 Genetically stable astaxanthin-producing P. pastoris strains (PpEBILWZ) were successfully constructed by introducing the carotenogenic genes crtW (β-carotene ketolase) and crtZ (βcarotene hydroxylase) into a β-carotene-producing P. pastoris strain (Pp-EBIL) which was previously engineered.96,97 P. rhodozyma is also identified as producing carotenoids such as echinenone, 3-hydroxyechinenone, and phoenicoxanthin. Molecular tools such as genetic engineering have also been applied to alter carotenogenic genes for overexpression of lycopene, β-carotene, ζ -carotene, and astaxanthin.98−100 According to ref 101, Sporobolomyces roseus (phylloplane yeasts) was discovered to synthesize β-carotene, torulene, and torularhodin. Also, other yeasts such as Sporobolomyces salmonicolor and Sporobolomyces patagonicus are carotenoid producers. A recent review102 outlines the microbial (yeast) production of carotenoids taking into consideration the use of low-cost substrates (whey, potato medium, etc.) from agro-industrial wastes as well as the factors influencing the production. Valduga et al.103 state that carotenoids synthesized by yeasts remain in the cells; therefore, additional cost must be incurred for the recovery resulting in high costs of production. 2.2.3. Cyanobacteria. Cyanobacteria are capable of synthesizing numerous bioactive compounds including carotenoids. These compounds are utilized by pharmaceutical companies as a template for developing cancer drugs. βCarotene, zeaxanthin, astaxanthin, echinenone, and myxoxanthophyll are found to be the predominant carotenoids produced by these cyanobacteria. Nevertheless, other carotenoids (ε-carotene, γ-carotene, lycopene, canthaxanthin, oscillaxanthin) are also synthesized.104−106 Gombos and Vig107 observed CrtQ and CrtP (homologous desaturase genes) to account for the synthesis of lycopene and ζ-carotene, respectively. β-Carotene (52%), zeaxanthin (38%), and small amounts of caloxanthin, cryptoxanthin, and nostoxanthin were found to produce by Synechococcus sp. (PCC7942). Thermosynechococcus elongatus and Prochlorococcus marinus were found to be the predominant producers of β-carotene and zeaxanthin. The strains also synthesize nostoxanthin and αcarotene, respectively. A significant volume of β-carotene was formed by Trichodesmium sp., with retinyl palmitate esterase identified as the main enzymes responsible for overexpression.108,109,31 Similar to algae, altering oxygen concentration and light intensity could stimulate the production of these carotenoids. Cultivating Calothrix elenkenii under lights resulted 5930


Review


homocarotenoids, and secocarotenoids are terms used to describe specific carotenoids produced by an organism which differs based on the number of carbon atoms.31 Enzymatic and chemical (nonenzymatic) oxidative cleavage of carotenoids produces unique biologically important carotenoid derivatives called apocarotenoids. It possesses the capacity to inhibit mammalian cancer cell proliferation thus changing gene expression.145,146 The removal of terminal methylene groups (CH3, CH2, or CH) from carotenoids results in the formation of norcarotenoids which include 2,2′-dinorβ,β-carotene and 12,13,20-trinor-β,β-carotene.31 Sasaki et al.147 isolated new norcarotenoids (trihydroxy-β-ionone and sechydroxyaeginetic acid) from steamed roots of Rehmannia glutinosa var. hueichingensis. Homocarotenoids (decaprenoxanthin) are exclusively synthesized by some bacterial organisms where isoprene is introduced into the C40 backbone (formed by more than eight units).148,149 Secocarotenoids are formed based on a triterpenoid, rather than the normal tetraterpenoid backbone due to fission reaction.31 Maoka et al.150 extracted three secocarotenoids from seeds of Pittosporum tobira. 2.4. Biosynthesis. Carotenoid biosynthesis is regulated throughout the life cycles of the plant, algae, fungi, bacteria, and lichens with dynamic changes in composition matched to prevailing developmental requirements and in response to external environmental stimuli. Basically, it involves a series of transformations which includes reactions, desaturation, cyclization, hydroxylation, epoxidation, and epoxidefuranoxide rearrangement (Figure 3). Carotenoids synthesis is catalyzed by 25 carotenogenic (Crt) genes. These proteins catalyze different reactions. The precursors for the MEP-(glyceraldehyde-3phosphate, pyruvate) and mevalonate pathway (acetyl-CoA) respectively, as well as of cofactors, such as ATP and NADPH,

Figure 2. Classification of carotenoids. Adapted with permission from Stephen, N. M. et al. Carotenoids: Types, Sources, and Biosynthesis in Plant Secondary Metabolites: Volume 2: Stimulation, Extraction, and Utilization; Siddiqui, M. W., Bansal, V., and Prasad, K., Eds. Copyright 2016 Apple Academic Press. http://www.appleacademicpress.com/ plant-secondary-metabolites-volume-2-stimulation-extraction-andutilization/9781771883542.

Currently, there are about 600 identified carotenoids (lipidsoluble tetraterpenoids). Xanthophylls (zeaxanthin, neoxanthin, violaxanthin, and siphonaxanthin) is the term assigned to carotenoids which contain oxygen and are separated from carotenes based on their polarity and are synthesized in the plastids. Also, their synthesis does not require sunlight, hence, are predominant in light-starved plants (young and etiolated leaves). Nevertheless, carotenoids free of oxygen are called carotenes (lycopene α-carotene, β-carotene) and are exclusively hydrocarbon. The orange hue pigments are vital for photosynthesis; hence, light is involved in the synthesis of carotene.16 Structurally, carotenoids differ based on functional groups, i.e., hydroxyl and epoxy, and are called carotenols and epoxy carotenoids, respectively. Apocarotenoids, norcarotenoids,

Table 3. Classes of Carotenoids Based on Their Structure, and the Presence of Functional Groupa Chemical structure presence/absence of oxygen Apocarotenoids

Acyclic carotenes

Cyclic carotenes

Epoxy-carotenoids

Carotenols

Presence of oxygen

Absence of oxygen

Retinol Bixin Crocin Apo-8′-β-carotenal Apo-8′-lycopenal Mycorradicin Cachloxanthin Galloxanthin Sinensiaxanthin Persicachrome Sinensiachrome Valenciaxanthin Cochloxanthin micropteroxanthins

ζ-Carotene Phytoene Lycopene Neurosporene Phytofluene Prolycopene 1,2-Dihydrolycopene Rhodopin Chloroxanthin Lycoxanthin Spirilloxanthin

α-Carotene β-Carotene γ-Carotene δ-Carotene α-Zeacarotene β-Zeacarotene Tethyatene Torulene Renieratene Isorenieratene Chlorobactene Renierapurpurin

Antheraxanthin Auroxanthin Luteoxanthin Neoxanthin Violaxanthin Fucoxanthin Flavoxanthin Mutatoxanthin Cryptoflavin Latoxanthin Salmoxanthin Dinoxanthin Diadinoxanthin Lutein-5,6-epoxide β-Carotene-5,6-epoxide β-Carotene-5,8-epoxide

α-Cryptoxanthin β-Cryptoxanthin Lutein Rubixanthin Zeaxanthin Zeinoxanthin Fucoxanthinol Siphonaxanthin Alloxanthin Diatoxanthin Parasiloxanthin Nostoxanthin Loroxanthin Saproxanthin Caloxanthin Crustaxanthin Nigroxanthin Rhodopinol Lactucaxanthin Gobiusxanthin

Antheraxanthin Astaxanthin Auroxanthin Canthaxanthin Capsanthin Capsorubin α-Crypoxanthin β-Cryptoxanthin Crocetin Lutein Luteoxanthin Lycophyll Lycoxanthin Neoxanthin Rubixanthin Tunaxanthin Violaxanthin Zeaxanthin Zeinoxanthin Salmonxanthin

α-Carotene β-Carotene δ-Carotene γ-Carotene Lycopene Neurosporene Phytoene Phytofluene α-Zeacarotene β-Zeacarotene

a

Adapted with permission from Stephen, N. M. et al. Carotenoids: Types, Sources, and Biosynthesis in Plant Secondary Metabolites: Volume 2: Stimulation, Extraction, and Utilization; Siddiqui, M. W., Bansal, V., and Prasad, K., Eds. Copyright 2016 Apple Academic Press. http://www. appleacademicpress.com/plant-secondary-metabolites-volume-2-stimulation-extraction-and-utilization/9781771883542.68 5931


Review


Figure 3. An overview of biosynthetic pathways of carotenoids in plant, algae, cyanobacteria, and bacteria. Modified with permission from ref 4333401464437 (John Wiley and Sons, 2016) and Stephen, N. M. et al. Carotenoids: Types, Sources, and Biosynthesis in Plant Secondary Metabolites: Volume 2: Stimulation, Extraction, and Utilization; Siddiqui, M. W., Bansal, V., and Prasad, K., Eds. Copyright 2016 Apple Academic Press. http://www.appleacademicpress.com/plant-secondary-metabolites-volume-2-stimulation-extraction-and-utilization/9781771883542.

pink-colored lycopene (11 conjugated double bonds). Depending on the species, desaturation can be fulfilled by phytoene desaturase (CrtP), ζ-carotene desaturase (CrtQ), and carotene isomerase (CrtH) in the case of plant and algae. In bacteria and fungi, phytoene desaturase (CrtI) is responsible whereas in green sulfur bacteria three enzymes (CrtP, CrtQ, and CrtH) catalyze the reaction.159−161 Following refs 31 and 162, the biogenesis pathways branch leading to the synthesis of various carotenoids. Transformation of acyclic lycopene is carried out by enzymes such as lycopene cyclases, ε-cyclase, and β-cyclase to synthesize α- and βcarotene, respectively. CrtY, CrtL, CruA, and CruP catalyzed the activities of lycopene cyclase. Carotenes (α- and β- carotene) serve as precursors for carotenoids such as xanthophylls, lutein, and zeaxanthin with the aid of β- and ε-ring specific hydroxylases (CrtG, CrtR) and β-ketolases (CrtO-mono

are synthesized via glycolysis which is important for the formation of 5-carbon (C5) isopentenyl-pyrophosphate (IPP) and dimethylallyl-pyrophosphate (DMAPP). Regulation of MEP is possible by two enzymes mainly, 1-deoxyxylulose-5phosphate synthase (DXS) and 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), whereas the mevalonate pathway is catalyzed by AtoB, MvaA, MvaS, Mvak 1&2, and MvaD. A central intermediate geranylgeranyl diphosphate (GGPP) is then synthesized, catalyzed by prenyl transferase (CrtE). A 40carbon phytoene is formed due to condensation of two GGPPs by phytoene synthase (CrtB).151−158,149 A desaturation reaction (dehydrogenation) occurs where double bonds are sequentially introduced at the side of phytoene to form a 5 conjugated double bond compound called phytofluene as well as ζ-carotene (7 conjugated double bonds), neurosporene (9 conjugated double bonds), and finally the 5932


Review

Journal of Agricultural and Food Chemistry Table 4. Carotenoids Extracted from Different Plant Materials Using Enzymesa Reference

Source

167, 168 169, 170

Marigold Chilli

171, 172 173 174 175, 176

Carrot Carrot spent Tomato Olives

177 177 177 177 177 177 167 167 167 167 167 168 168 168 168 178

Tomato Tomato Tomato Tomato Tomato Tomato Marigold Marigold Marigold Marigold Marigold Tagetes erecta Tagetes erecta Tagetes erecta Tagetes erecta Marigold Flowers Marigold Flowers Marigold Flowers Tomato pastes Tomato pastes Tomato pastes Tomato pastes

178 178 179 179 179 179 a

Carotenoids

% increase in yield over conventional method

Enzymes used

Lutein carotenoids and capsaicin Carotenes Carotenes Lycopene Chlorophyll Carotenoids Lycopene Lycopene Lycopene Lycopene Lycopene Lycopene Carotenoids Carotenoid Carotenoids Carotenoid Carotenoids Carotenoids Carotenoids Carotenoids Carotenoids Carotenoids

Cellulase, hemicellulase pectinase 0.01−0.1%w/w Cellulase, hemicellulase, Pectinase

2−5-fold increase carotenoid-11, capsaicin-7

Pectinase, cellulase Pectinase + hemicellulose Pectinase, cellulose Pectinase + hemicellulose

41−49 _ 20 _

Celluclast/Novozyme Viscozyme Flavourzyme Celluclast/Novozyme + Viscozyme Celluclast/Novozyme + Flavourzyme Celluclast/Novozyme + Viscozyme + Flavourzyme Rapidase-Press Pectinase-Cep Econase-cep Cytolase-0 Cytolase-m129 Viscozyme Viscozyme + HT-Proteolytic Viscozyme + HT-Proteolytic + Pectinex Viscozyme + HT-Proteolytic (silaged flower) Cellulase 0.5 mL/100 g

18−22 18−22 18−22 ∼153 44−67 44−67 _ _ _ _ _ ∼85 ∼90 ∼98 ∼100 _

Carotenoids

Cellulase + Hemicellulase + Pectinase 0.5 mL/100 g−0.2 g/100 g−0.5 mL/100 g

_

Carotenoids

Cellulase + Hemicellulase + Pectinase 0.8 mL/100 g−0.4 g/100 g−0.8 mL/100 g

_

Lycopene

Citrozym Ultra L

∼40

Lycopene

Peclyve LI

∼85−90

Lycopene

Peclyve EP

∼75−80

Lycopene

Citrozym C

∼65−70

Modified with permission from ref 4345950156258 (Taylor & Francis, 2010).177−179

are embedded.166 Each enzyme has a specific function subsequently; plant materials utilized in extracting carotenoids require different enzymes for effective destruction of cell walls in order to release the carotenoid with cellular fluids. Table 4 shows carotenoids obtained from different sources with the aid of enzymes. The merits of enzymatic extraction include the following: (1) reduced extraction time; (2) enhanced extractability/yield; (3) minimized quantity of solvent involved in extraction/in some circumstances elimination of solvent totally, when vegetable oils are utilized as solvents; (4) it is environmentally friendly and does not arouse criticism; (5) renewable (enzyme can be purified and reuse); (6) relatively cheaper than organic solvents; (7) enzymes are flexible and specific; (8) many reactions can be achieved with a few enzymes. The main drawbacks of this method are enzymes are expensive to purchase, liable to degradation, and hence, care should be taken not to exceed the maximum operating temperature specified by the manufacturer. Tomato tissue is composed of pectin and cellulose hemicellulose, and enzymes applied have pectinolytic, cellulolytic, and hemicellulolytic activities respectively, consequently enhancing the extractability of lycopene 6-fold when compared to an untreated sample.178

ketolase, CrtW). The activity of an enzyme violaxanthin deepoxidase leads to introduction of an epo side group to transform zeaxanthin to violaxanthin.47,16 Homocarotenoids (i.e., flavuxanthin) and apocarotenoids (i.e., neurosporaxanthin) are able to be synthesized by bacteria and fungi, respectively, with the former and latter catalyzed by enzymatic activities of lycopene elongase and carotenoid oxygenase. Flavuxanthin serves as the precursor to synthesize decaprenoxanthin by the action of ε-cyclase.163,31 It is estimated that about 108 tons/ year of carotenoids are produced, mainly lutein, violaxanthin, neoxanthin, and fucoxanthin (predominant in macroalgae and microalgae).164

3. METHODS OF EXTRACTING CAROTENOIDS 3.1. Enzyme-Based Extraction. The enzyme-based extraction method mainly depends on the selection of appropriate enzymes (pectinase, cellulase, etc.), optimum operational conditions (temperature, pH, etc.), and the substrate (material). According to ref 165, the yield of lycopene increased up to 20 times higher as compared to other methods via optimal enzyme concentration and process time. Enzymes have the ability to destroy the structure of plant cells which houses the chloroplast membrane from which the carotenoids 5933


Review

Journal of Agricultural and Food Chemistry Roberts180 states that the architecture of the plant cell wall constitutes cellulose, a linear polymer of β-1,4-linked glucose, and hemicelluloses, which form a fairly rigid network that interacts with a gel-like matrix of hydrated pectin substances. Degradation of this polysaccharide creates a pore space for solvent penetration into the plant products inevitably improving the efficiency and yield of carotenoids.178 A well documented literature review on application of enzymes in the extraction of oil from sunflower and soybean, rapeseed, corn, coconut, olives, avocado, including extraction of rice bran oil, etc. has been revised in refs 181−185, and Lenucci et al.177 reported that the combined use of food-grade commercial plant cell-wall glycosidases improved considerably the extraction of lycopene oleoresin from the tomato matrix. The highest titer (30.6 ± 2.1 mg cm−3) of lycopene of the hydrolyzed matrices was detected in the treatment with Celluclast/Novozyme + Viscozyme followed by Celluclast/Novozyme + Viscozyme + Flavourzyme (30.1 ± 2.3 mg cm−3). However, Celluclast/ Novozyme + Flavourzyme, Celluclast/Novozyme, and Viscozyme also gave better yields (21.2 ± 1.5, 18.1 ± 1.3, 16.1 ± and 1.5 mg cm−3, respectively) whereas the lowest titers were associated with Flavourzyme (8.7 ± 0.6 mg cm−3) and the control (8.3 ± 0.8 mg cm−3). Dominquez et al.182 reported an increase in yield and quality of oil when they applied enzymes to oilseeds during extraction of oil. Their work also pointed out the merit of using enzymes over the conventional solvent methods which is generally problematic in terms of efficiency and purity. Food industries have utilized these enzymes for decades, in winemaking, brewing beer, starch processing, ripening cheese, the transformation of starch to high fructose corn syrup and to obtain ferulic acid from sugar beet pulp.186 Ç inar187 assessed the effects of different enzyme (cellulase, pectinase) concentrations and time during extraction of carotenoids from carrots, sweet potatoes, and orange peels. From the experimental results, she concluded that the maximum carotenoid yield was obtained by the combination of 5 mL pectinase/100 and 0.1 g cellulase/100 g in orange peels followed by sweet potatoes (5 mL pectinase/ 100 g, 1 g cellulase/100 g for 12 and 18 h, respectively). The application of enzymes (pectinase and cellulase) destroyed the cell wall of plant materials (orange peels, sweet potatoes, and carrots) prompting the release of carotenoids with other watersoluble pigments. Barzana and colleague168 utilized enzymemediated solvent extraction to recover carotenoid from Tagetes erecta. They recorded 50% losses due to silaging, drying, and solvent extraction. It was recommended that addition of a substantial volume of water for enzyme hydrolysis was unnecessary and should be avoided in further work. 3.2. Supercritical Fluid Extraction (SFE). The use of organic solvents in food processing has raised major public health, safety, and environmental concerns. Thus, there are growing consumer concerns for the fear of solvent residue remaining in the final food, and this warrants strict state regulation. One of the ideal alternate extraction methods proposed to decrypt the above-mentioned issues was the supercritical fluid extraction (SFE) technology. Some fluids that were utilized include carbon dioxide, ethane, propane, butane, pentane, ethylene, ammonia, sulfur dioxide, water, chlorodifluoromethane, etc. Due to consumer concerns and other criticisms, usage of water and carbon dioxide as traces of solvent in the end product alleviates this problem.188−192 The physical properties of common solvents used in SCFE are detailed in refs 192 and 193. Rizvi et al.194 state that

supercritical carbon dioxide (SC-CO2) is the most preferred method of extracting carotenoids (natural products) for pharmaceuticals and food industries. Carbone dioxide is noncorrosive, inert, inexpensive, nonflammable, availability, odorless, tasteless, environmentally friendly, and generally regarded as safe (GRAS). SC-CO2 has been successfully applied in extracting carotenoids. Optimizing the yield is a function of many independent factors; therefore, solvent flow rate, resident time, moisture content, and particle size distribution in combination with supercritical pressures (Pc) and temperatures (Tc) are crucial parameters to carefully adhere to. These parameters have individual or combined effects on extractability (yield) of a particular plant material. Consequently, modeling these parameters had been recently tasked in the scientific community to decipher ways of optimizing yield.189 Uquiche and co-workers191 modeled some parameters to optimize the yield of carotenoid pigments. Literature details of the model can found in ref 195. The solubility properties of the supercritical fluids are greatly affected by its density, diffusivity, and viscosity (at a pressure of 5−50 MPa and temperature of 300 °C).196 The literature reviewed in ref 197 revealed the solubility potentials of CO2 are similar to those of solvents such as acetone and chloroform. Materials are loaded into the stationary phase via extraction column while extraction occurs in the separation phase. SCFE utilizes compressed gases above their critical pressure (Tc) and temperature (Tc). The solutes (carotenoids) are dissolved by these fluids in the solid bed for harvesting. An investigation198 revealed that the direction of flow of the SCF via a fixed bed can be vertical or horizontal. Moreover, at high solvent ratios (ratio of the flow of SCFE to the amount of solid material) the influence of gravity is insignificant. Bioactive compounds, i.e., antioxidants, flavonoids, lycopene, essential oils, lectins, carotenoids, etc., have successfully been extracted from a variety of biological materials using the technology of SCE.189 This technology was applied to obtain vitamin additives and herbal medicine, dealcoholize beverages, and defat potato ships which are all found on our tables daily.198 Details of the processes can be found in refs 199−204. Some known applications of SCFC technology are tabulated in ref 192. Merits of SC−CO2 overwhelm its demerits and are stated in ref 189 as (a) possessing solvation potentials similar to organic solvent and higher diffusivities; (b) easier to control thus separation can be altered by simply changing the operating pressure or temperature; (c) selective and separation power can be enhanced by modifying CO2 with cosolvents, and solvating potentials could be extended to polar components; (d) possibility of mild extraction conditions combined with low energy requirements for solvent recovery.205 High capital investment and the complex operating system have limited the utilization of this technology. Nevertheless, advocacy for SC-CO2 is on the rise due to recent advancement in the equipment, processing, and demand for high-value products which are seen to be profitable for processing industries.189 Lycopene is susceptible to light, heat, and oxygen, including acids and bases. When extracted from tomatoes by SC-CO2, isomerization and degradation were minimized as compared with conventional solvent extraction (CSE).206 Carotenoids were also extracted from red pepper (Capsicum annuum L.) oleoresin by this technology.191 From literature,207,208 red pepper oleoresins are composed of light (e.g., fatty oils) and 5934


Review


°C until no further headway was observed when increasing the temperature. The increase in yield was a result of the complex interaction between density which decreased and prompted poorer solvating potential. The productivity and cost viability of SCFE can be enhanced by applying cosolvents (entrainers). Using 1−5% cosolvent can significantly change the properties of the extraction fluid.189 The significant interaction between the indirect effect (cosolvent−solvent) and direct effect (cosolvent−solute) hase been indicated in ref 219. From previous work,189,192 these changes significantly altered the density and compressibility of the original fluids used in SCFE. Furthermore, they enhanced the selectivity of desired components and fractional separation potentials. Previous work220 utilized ethanol, methylene chloride, and methanol. It was determined that ethanol had the greatest enhancement factor whereas methanol had the lowest. For more information on the cosolvent in the SC-CO2, refer to literature, in particular, refs 205 and 221−224. Cosolvents should not hinder the specific purpose for application. An increase in solvent loading resulted in the coextraction of undesirable compounds221 which contaminated target compounds (carotenoids, etc.). Functional properties and food formulated with these extracts (carotenoids) could be altered due to these undesirable compounds. Nevertheless, SC-CO2 offers a novel approach in extracting compounds of interest without traces of organic solvent. Mongkholkhajornsilp et al.225,226 modeled extractions of ninbin from neem seed using SC-CO2. According to their results, the models helped to estimate the trend of extraction. Models could be useful in optimizing the yield since factors (mass transfer coefficient, cosolvent, temperature, and pressure) could contribute negatively to the extraction process. Moreover, experimental data gathered during extraction could be thus validated. 3.3. Microwave-Assisted Extraction (MAE). MAE of carotenoids is unique in relation to traditional techniques; extraction occurs as a result of changes in cell structure caused by electromagnetic waves.227 This method is a straightforward, quick, and economic strategy for carotenoid extraction, requiring less extraction time and low volumes of solvents228,229 which reduce pollution and cost. Microwave extraction has been subdivided into microwave-assisted solvent extraction (MASE) and microwave solvent-free extraction (MSFE). Due to denunciation by consumers and ecologists, the latter is preferred. MASE operates when materials (plants) and solvents (ethanol, methanol, water) are mixed and subjected to microwave energy and samples ared heated to a boiling point where the solvents eventually enter into the plant materials. Target compounds (carotenoids) are then solubilized and leached out. Samples absorbed heat via conduction and convection. Microwaves present a controllable source of energy. Paré patented a technology known as the microwaveassisted process (MAP), where the sample is first wet with solvents. By means of direct heating, target compounds (carotenoid) escape from the sample matrix and drip into a collection flask. The MAP has been successfully utilized in extracting oils and coloring agents for cosmetics and food industries. MASE requires less solvent and energy, thus receiving fewer criticisms than CSE.230−234 Microwave hydrodiffusion and gravity (MHG), also known as green extraction, is a type of MSFE which was developed for carotenoid extraction. This method depends on the “upsidedown” microwave alembic coupled with heating and earth

heavy constituents (e.g., pigments). Uquiche et al. 191 discovered that the total carotenoid yield depends on how these fractions (constituents) are extracted from the red pepper. An increased pressure from 320 to 550 bar witnessed a significant extraction of the heavy component due to the excessive solubility at high pressure. SC-CO2 extraction at 40 °C is estimated to exhibit a solubility of 1.2 mg/kg at 320 bar and 1.9 mg/kg at 540 bar, respectively, while for lycopene (red carotenoid pigment in tomato) it is estimated as 1.4 and 2.6 mg pigment/kg CO2 at 320 and 540 bar, respectively.209 Durante et al.210 deal with the results acquired during the extraction oil rich in carotenoids from a pumpkin. Furthermore, the results were compared with CSE. They observed that SCCO2 resulted in much higher efficiency than CSE in terms of the solid−liquid ratio, temperature, extraction time, and oil yield obtained. Nevertheless, the addition of comatrix (milled pumpkin) advanced the yields. The concentration of carotenoids in pepper determined by HPLC was doubled due to an increase in extraction pressure (from 320 to 540 bar) which followed the trend of β-carotene and lycopene solubility in SC-CO2 with pressure. By comparing the quantities of carotenoids extracted and the utilization of SC-CO2, it can be estimated that ∼0.9−2.9 mg pigment/kg CO2 was used, thus, recommending the solubility-controlled extraction of carotenoid pigments.191 The ratio of lycopene to β-carotenes increased with increasing pressure from 2.7 at 320 bar to 3.7 at 430 bar, and to 3.9 at 540 bar which supports the work of Uquiche and his colleagues. Light red oleoresins (Lycopene) that were obtained were concentrated compared to the red color (β-carotene) when extracted with SC-CO2 at 40 °C and 320 bar and at 40 °C and 430 or 540 bar, respectively (Table 5).207,191 Bashipour and Ghoreishi211 optimized the following parameters (333.15 K, 29 MPa, and 1 mL CO2/min) and obtained the higher yield of β-carotene 0.3524 g βcarotene/kg dry sample. Multiple papers have been published on various aspects of optimizing conditions for SC-CO2 extraction of carotenoids.212−218 According to ref 193, an increase in temperature up to 46 °C optimized the yield of lutein, but beyond (60 °C) it started to decline. Maximum yield was achieved at 300 and 500 bar in 39 Table 5. Concentration of Carotenoid Pigments in Red Pepper Oleoresins Obtained with SC-CO2a SC-CO2 Pigment concentration (g carotenoid pigment/ kg oleoresin) HPLC analysis Total concentration Total concentration of red pigments Capsorubin Capsanthin Capsanthin 5,6 epoxide Zeaxanthin Cryptocapsin Total concentration of yellow pigments β-Cryptoxanthin β-Carotene Spectrophotometric analysis (total concentration)

330 bar

430 bar

540 bar

3.65 2.66 0.21 0.75 0.39 0.94 0.37 0.99 0.35 0.64 20.1

7.01 5.53 0.89 0.84 1.33 2.08 0.39 1.48 0.83 0.65 27.0

7.66 6.08 1.10 0.91 1.04 2.41 0.62 1.58 0.89 0.69 31.6

a

Adapted with permission from ref 4333390128071 (Elsevier, 2004).191 5935


Review


solvent. When the solvent is heated, the vapor travels via the distillation path of the extractor and then condense back onto the plant materials. Via siphon exit, the extract solvent/vapor falls back into the round-bottom flasks. The process is replicated until complete extraction is achieved. Degradation of target compounds was minimized by a condenser with running water attached to the extractor for cooling. This technology is mostly applied to evaluate the efficiency of other conventional techniques. Moreover, it is suitable for extracting thermostable compounds because of the high temperatures involved.241−244,16 SE assisted by ultrasound has the feasibility to extract more sample mass than ME.245 Filtration is not obligatory when using SE. Moreover, it allows for continuous extraction since there is constant contact between the sample and extracting solvent. Nevertheless, it is not economical beause it is time consuming and requires large volumes of extracting solvents. As cited in ref 229, the high possibility of thermal degradation and cis−trans isomerization of carotenoids is due to high temperatures and prolonged extraction time. For this reason, a modified Soxhlet apparatus, aimed at overcoming the drawbacks of a conventional Soxhlet extractor, was proposed.246 Bangun et al.247 extracted carotenoids from crude palm oil (CPO) using magnesium and calcium silicates and polystyrenesulfonates [PSS] as absorbents via a Soxhlet extractor. The maximum carotenoid yield was obtained after 40−50 cycles with the aliquots. Amounts of 62.24%, 43.45%, 30.02%, and 78.02% of carotenoids were extracted via Mgsilicate, Ca-silicate, Mg-PSS, and Ca-PSS absorbents, respectively. Toluene was used to stabilize the extracted carotenoids. Yahaya also used this method to extract carotenes from carrots with 2-propanol as the extraction solvent.248 Solvents (nhexane, ethanol, acetone, isopropanol, and isopropanol/ hexane) in a ratio of 50:50 v/v were utilized in the extraction of carotenoids from pink shrimp (P. brasiliensis and P. paulensis) byproduct after subjecting the samples to pretreatment (cooking, drying, milling). Different extraction methods were applied in conjunction with Soxhlet extraction. From the results, it was revealed that pretreatment significantly affected the yield. Furthermore, cooking broke the bond in the carotenoid−protein complex. A high yield of astaxanthin was obtained by Soxhlet with hexane/isopropanol (21 ± 1 μgastaxanthin/g RM) and with acetone (20 ± 2 μgastaxanthin/g RM).249 β-Carotene was extracted from lyophilized skin powder of aloe vera by Soxhlet extraction, with petroleum ether as solvent (100 mL) and an extraction time of 8 h.211 3.5. Ultrasonic Assisted Extraction (UAE). Ultrasound is waved ranged between 20 kilohertz (kHz) to several gigahertz (GHz). Commercial application of UAE has witnessed global acceptance, process improvements, and a drastic reduction in maintenance cost.250 Pingret et al.251 reported that the energy requirement is comparatively low compared to other industrial equipment although this depends on the application. As cited in refs 252 and 253, utilization of UAE enhanced the yield and efficiency of extraction due to acoustic cavitation destroying cell walls, releasing carotenoids and water-soluble pigments out of the cells. Maximum betacyanin (1.42 ± 0.001 mg/g) and betaxanthin (5.35 ± 0.13 mg/g) were obtained from Basella rubra. L using UAE (extraction temperature, 54 °C; ultrasonic power, 94 W; extraction time, 32 min; solid to liquid ratio, 1:17 g/mL).254 Purohit and his colleague coupled UAE with intermittent radiation to extract carotenoids from carrot residue. Maximum

gravity at atmospheric pressure for its operation. It involves putting plant material in a microwave reactor, without solvents. Microwaves from this reactor heat up plant cells and prompt the burst of oleiferous repositories and organs, consequently freeing secondary metabolites (carotenoids) for extraction via the perforated Pyrex disc. Due to the heating involved, a cooling system is required outside the microwave oven for cooling the extract before harvesting,235,230 which could curtail degradation and isomerization of carotenoids. All-trans-lycopene was extracted by MAE utilizing ethyl acetate in a solid to liquid ratio of 20:1 (v/w) and power of 400 W for 1 min from tomatoe peels. The yield increased as the ratio decreased by minimizing another solvent, i.e., hexane, while increasing ethyl acetate. Based on the results, ethyl acetate was suggested as the solvent of choice rather than hexane in MAE due to its high extract recovery. Despite the merits of MAE over CSE, degradation of carotenoids cannot be ignored. However, a cooling system has been proposed outside this microwave oven via the collection tubes to stabilize carotenoids.236 Rearrangement of carotenoid molecules occurs at the temperature of 60 °C. Moreover, at this temperature, a phenomenon known as thermooxidation occurs where hydrophobic carotenoids are oxidized into hydrophilic carotenoids. Different extraction steps were studied, and the results demonstrated that more than one extraction step was needed to fully prompt the release of carotenoids from paprika powders using either MAE or CSE. Notwithstanding, the results also indicate the physiochemical properties of the solvents (cosolvent) should be factored in when calculating the regression coefficient of MAE.237 According to refs 238 and 239, the key factor in enhancing the efficiency of extraction is the structure of the plant materials. Therefore, pretreatment of the materials (chemical, biological and mechanical treatment) was the way forward in improving carotenoid yield. Blanching carrots with water and citric as a treatment before MAE resulted in a significant increase in yield of carotenoid and antioxidant activity compared to untreated samples. The pretreatment aided the destruction of the carrot cell wall, consequently creating pores via which carotenoids in the chloroplasts are leached out for extraction.238,229 Application of intermittent microwave radiation coupled with MAE was utilized in extracting carotenoids and β-carotene from carrot peels with varying parameters such as microwave power (180 or 300 W) and solvent volumes (75 or 150 mL) through increased diffusivity of the solvent by increasing the temperature.228 A two-step modeling approach was adopted in ref 240 in a study to compare the MAE and conventional Soxhlet extraction (SE) of bioactive compounds from Adathoda vasica and Cymbopogon citratus. The yields of both methods were similar; however, the time spent to attain the compounds via MAE and Soxhlet extraction were 210 s and 10 h, respectively. However, the yield of C. citratus by MAE was significantly higher than that by SE when the parameters were optimized (1:20 sample/solvent ratio, extraction time of 150 s, and 300 W output power). Thermal degradation has been distinguished as one of the drawbacks associated with MAE, as it reduces the bioavailability and health benefits of carotenoids. For this reason, intermittent radiation as a better alternative for minimizing thermal degradation, higher recovery, and improved antioxidant activities of extracts was recommended.228 3.4. Soxhlet Extraction. Franz Von Soxhlet invented an extractor composed of a thimble which houses plant materials and is connected to a round-bottom flask containing extraction 5936


5937

Cohort Study

Cohorts study Cohorts study

Randomized controlled crossover trial Cohorts study Cross-sectional study

A Case-Control Study Case-Control Study

Cross-sectional study

Hospital based casecontrol Hospital-based casecontrol study Cohorts study

Cohort Study

Design

α-carotene β-carotene, α-carotene, β-cryptoxanthin, lutein/zeaxanthin and lycopene β-carotene β-carotene, α-carotene, lutein, β-cryptoxanthin, lycopene α-carotene, β-carotene, lycopene, lutein/ zeaxanthin

α-carotene, β-carotene, lutein plus zeaxanthin, lycopene, β-cryptoxanthin α-carotene, β-carotene, lutein/zeaxanthin, lycopene, and β-cryptoxanthin α-carotene, β-carotene, lutein/zeaxanthin, lycopene, β-cryptoxanthin β-cryptoxanthin, lycopene, lutein and zeaxanthin, sum of all carotenoids β-cryptoxanthin, lycopene, lutein plus zeaxanthin, β-carotene and α-carotene Carotenes Lycopene, α-carotene, β-carotene, β-cryptoxanthin, lutein, and zeaxanthin β-carotene

Carotenoids involved

Italy The Netherlands Brazil

1993−1997 merged in 2007 2011

2007 1988−1990, and 1992 1986−1992 The Netherlands

Finland USA

Japan USA

Australia

2013−2014 1989−2009 2001−2006

China Vietnam

2013−2016 2013−2015

2010 1992−2008

Location The Netherlands China

Year 1986−2006

Table 6. Studies on Carotenoid Intake and Health Concerns

Food frequency questionnaire

Questionnaire Phase 1: Clinical trial. Phase 2: Interviewer-administered questionnaires Questionnaires Food frequency questionnaire


Food frequency questionnaire Food frequency questionnaire



Questionnaire


Questionnaire

Carotenoid Intake assessment

Prostate cancer

Aerodigestive tract cancers Prostate cancer.

Prostate cancer Prostate cancer

Skin Yellowness

DNA damage (lipid oxidation and oxidative stress markers) Primary liver cancer Prostate Cancer

Type 2 diabetes

Nasopharyngeal carcinoma

Colorectal cancer

Head and Neck Cancer

Type of health concern

58 279 (642)

29 133 47 894 (812)

15 471 (143) 134

31

644 652

296

37846 (915)

792

585

5000

Sample size (Incidence recorded)

280

278 279

276 277

275

273 274

272

271

270

269

268

Reference

Journal of Agricultural and Food Chemistry Review


Review


30% and 50% losses of β-carotene and other carotenoids, respectively, were registered due to saponification. Similar results were obtained265,266 when they could not recover sufficient β-carotene from table olives. Granado et al.266 developed a “shortcut” (small volumes, vortex 3 min, 20% potassium hydroxide, hexane/methylene chloride extraction) protocol for saponification. The results confirmed the “shortcut” saponification was accurate like the standard protocol. Moreover, the shortcut was cheaper and easier to perform, many samples can be treated, and operation is carried out at standard room temperature. Saponification is encouraged when working with lipid-rich samples.267 Saponification is less applied for extracts which are meant for the cosmetics industries.

β-carotene at 83.32% and 64.66% was obtained via ultrasound irradiation and ultrasonic bath, respectively; a solvent with medium vapor pressure, low viscosity, and surface tension performed best.253 A cheaper, simple-to-use technique of carotenoid extraction was developed and reported in ref 255 (termed: green UAE). Maximum β-carotene (334.75 mg/L) was achieved in 20 min with sunflower oil as the solvent, and CSE gave 321.35 mg/L at 60 min. Goula et al.256 optimized the yields of carotenoid from pomegranate peels. It was revealed that the maximum yield was achieved with the following parameters: extraction temperature, 51.5 °C; peels/solvent ratio, 0.10; amplitude level, 58.8%; solvent, sunflower oil. In summary, using sunflower oil as a solvent in UAE will approximately extract 85.7−93.8% of carotenoids in materials; moreover, it is environmentally friendly. Ultrasound and magnetic stirring methods were compared in ref 257 during extraction of natural dye from carrots. UAE gave a better yield because ultrasound assisted the mass transfer via the solvent. Luo258 extracted ginsenosides using UAE in supercritical CO2 reverse microemulsions. The results showed altered process kinetics and an improved yield of ginsenoside at 20 kHz, 15.2 Wcm−2, and 3/6 s. Kumcuoglu et al.259 compared UAE with conventional organic solvent extraction (COSE) when they extracted lycopene from tomatoe waste. The solvents used included hexane/acetone/ethanol (2:1:1) with 0.05% (w/v) butylated hydroxytoluene (BHT). The maximum yields were obtained at a liquid−solid ratio of 35:1 (v/w) with an ultrasonic power of 90 W, whereas in COSE a 50:1 (v/w) liquid−solid ratio, 40 min extraction time, and 60 °C temperature gave the best results. The authors also noted that each parameter applied in both methods significantly affected the yield.

5. HEALTH CONCERNS WITH CAROTENOIDS INTAKE There have been several reports about carotenoids having some links with cancer and other ailments. This serious concern has resulted in researchers and funding bodies already responding to this challenge. A simple search of known databases without restriction using keywords such as “carotenoid intake cancer risk” resulted in about 38 300, 1110, 761, and 913 results for Google Scholar, Scopus, Web of Science, and PubMed, respectively. Table 6 shows recent work related to carotenoid health concerns. Conversion of β-carotene to retinol was altered due to excessive alcoholism. In another study, alcohol addicts had a higher risk of lung cancer (RR = 1.16; 95% CI = 1.02−1.33; p = 0.02, logrank test) when supplemented with a high dose of βcarotene.281−283 Heavy smokers had the higher chance of developing lung cancer when supplemented with 20 or 30 mg/ day of β-carotene.284 Cholesterol-lowering drugs such as atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), and pravastatin (Pravachol) could not metabolize/ function appropriately when taken along with carotenoids (βcarotene). Moreover, the intake of β-carotene with vitamins and selenium suppressed some beneficial effects of niacin. Cholesterol levels increased as niacin interacted with carotenoids.285,286 Van den Berg287 carried out a comparative study with β-carotene and lutein in ratios of 2:1 and 1:2, respectively. The results revealed lutein had an inhibitory effect when it was the predominant carotenoid. In plasma serum studies, β-carotene exerted an inhibitory effect over lutein. Evidence of carotenoid interaction was observed in ref 288 when a rat was fed with different ratios of β-carotene and xanthophylls (lutein). A decrease in Vitamin A deposition in the liver was observed at a low β-carotene and xanthophylls (lutein) ratio (1). Canthaxanthin was also reported to have altered β-carotene absorption.289 A strong inverse association with pancreatic cancer risk was established with higher dietary intake of antioxidants including selenium, vitamin C, vitamin E, β-carotene, and β-cryptoxanthin.290 Lu et al. reported contradictory findings in their research. Intake of α-carotene, β-carotene, β-cryptoxanthin, and lycopene was inversely associated with colorectal cancer risk. However, no significant association was found with lutein/ zeaxanthin intake and colorectal cancer risk.269 Umesawa et al.276 states that moderate to high α-carotene intakes might contribute to minimizing the risk of prostate cancer among the Japanese population. This is in agreement with results obtained by several authors.291,268,292,293

4. SAPONIFICATION Application of carotenoids in food and pharmaceutical industries requires quantification. But carotenoids are extracted with other undesirable compounds (lipids, fatty acids, chlorophylls) which are embedded in the cell components. These undesirable compounds could interfere with equipment readings giving false results. For this reason, saponification is practiced to eliminate compounds which could affect any analytical readings by equipment, i.e., Ultraviolet−visible spectrophotometry (UV−vis), high-performance liquid chromatography (HPLC), high-performance thin layer chromatography (HPTLC), nuclear magnetic resonance (NMR), thin layer chromatography (TLC), Fourier transform infrared spectroscopy (FTIR), and ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS). According to ref 260, carotenoids are esterified in materials (fruits/vegetables) by fatty acids and, hence, must be eliminated. Carotenoids such as carotene exist in free form whereas xanthophylls are acylated with saturated and unsaturated fatty acids. The esterified xanthophylls with other undesirable substances can contribute to a false reading on chromatograms,261,229 which is not acceptable in the scientific community. Effective saponification was achieved with 2% methanolic KOH (w/v) after 6 h beyond which degradation started to occur.262 Extraction and saponification also preferably should be carried out separately, as this gave better results. Saponification was shown to increase the recovery of βcarotene and lutein.263 Based on the raw material, saponification can also lead to losses of carotenoids. For instance,264 20− 5938


Review

Journal of Agricultural and Food Chemistry Hayhoe et al.294 carried out a cohort study investigating carotenoid dietary intake and osteoporotic fracture risk. The results showed that carotenoids were all inversely associated with hip fracture risk in men, and significantly, associations were identified for women. This goes to support previous work.295 Lung cancer was noted to decrease due to an intake of βcarotene, α-carotene, β-cryptoxanthin, lycopene, and vitamin C.296 A recent meta-analysis297 supports these findings. However, high intakes of lutein/zeaxanthin did not significantly lower the risk of lung cancer as reported in refs 298−302. According to ref 303, African-American (AA) and AfricanCaribbean (AC) men are known to have the highest prostate cancer incidence rates compared with other racial groups. This finding should be an automatic call for Africa as a continent to start researching preventative measures especially with carotenoids. However, throughout our research, we could not find any related research that is carried out in Africa. We are, therefore, taking this opportunity to alert the Africa Union and the countries within it to consider funding similar research for the betterment of its citizens and the world as a whole.

raphy; NMR, nuclear magnetic resonance; TLC, thin layer chromatography; FTIR, Fourier transform infrared spectroscopy; UPLC-MS, ultraperformance liquid chromatographytandem mass spectrometer; TCP, thermodynamic critical points; GRAS, generally regarded as safe; DXS, 1-deoxyxylulose-5-phosphate synthase; DXR, 1-deoxy-D-xylulose 5-phosphate reductoisomerase; UV, ultraviolet.

■

(1) Rao, A. V.; Rao, L. G. Carotenoids and Human Health. Pharmacol. Res. 2007, 55 (3), 207−216. (2) Nelis, H. J.; De Leenheer, A. P. Microbial sources of carotenoid pigments used in foods and feeds-a review. J. Appl. Bacteriol. 1991, 70 (3), 181−191. (3) Lamers, P. P.; Janssen, M.; De Vos, R. C. H.; Bino, R. J.; Wijffels, R. H. Exploring and exploiting carotenoid accumulation in Dunaliella salina for cell-factory applications. Trends Biotechnol. 2008, 26 (11), 631−638. (4) Frengova, G. I.; Beshkova, D. M. Carotenoids from Rhodotorula and Phaf f ia: yeasts of biotechnological importance. J. Ind. Microbiol. Biotechnol. 2009, 36 (2), 163−180. (5) Di Mascio, P.; Kaiser, S.; Sies, H. Lycopene as the Most Efficient Biological Carotenoid Singlet Oxygen Quencher. Arch. Biochem. Biophys. 1989, 274 (2), 532−538. (6) Tinkler, J. H.; Bohm, F.; Schalch, W.; Truscott, T. G. Dietary carotenoids protect human cells from damage. J. Photochem. Photobiol., B 1994, 26 (3), 283−285. (7) Arab, L.; Steck, S. Lycopene and cardiovascular disease. Am. J. Clin. Nutr. 2000, 71 (6), 1691S−1695S. (8) Hadley, C. W.; Miller, E. C.; Schwartz, S. J.; Clinton, S. K. Tomatoes, lycopene, and prostate cancer: progress and promise. Exp. Biol. Med. 2002, 227 (10), 869−880. (9) Heber, D.; Lu, Q. Y. Overview of mechanisms of action of lycopene. Exp. Biol. Med. 2002, 227 (10), 920−923. (10) Mayne, S. T. Beta-carotene, carotenoids, and disease prevention in humans. FASEB J. 1996, 10 (7), 690−701. (11) Lee, J.; Jiang, S.; Levine, N.; Watson, R. R. Carotenoid supplementation reduces erythema in human skin after simulated solar radiation exposure. Proc. Soc. Exp. Biol. Med. 2000, 223 (2), 170−174. (12) Zakaria, H.; Simpson, K.; Brown, P. R.; Krotulović, A. Use of reversed phase HPLC analysis for the determination of provitamin A carotenes in tomatoes. J. Chrom A 1979, 176 (1), 109−117. (13) Saeid, A.; Eun, J. B.; Sagor, S. A.; Rahman, A.; Akter, S.; Ahmed, M. Effects of Extraction and Purification Methods on Degradation Kinetics and Stability of Lycopene from Watermelon under Storage Conditions. J. Food Sci. 2016, 81 (11), C2630−C2638. (14) Ciriminna, R.; Fidalgo, A.; Meneguzzo, F.; Ilharco, L. M.; Pagliaro, M. Lycopene: Emerging Production Methods and Applications of a Valued Carotenoid. ACS Sustainable Chem. Eng. 2016, 4 (3), 643−650. (15) United States Department of Agriculture. United State Department of Agriculture Report 2016: National Nutrient Database for Standard Reference. Washington, United State of America: United States Department of Agriculture; 2016. (16) Singh, A.; Ahmad, S.; Ahmad, A. Green extraction methods and environmental applications of carotenoids-a review. RSC Adv. 2015, 5, 62358−62393. (17) Fatimah, A. M. Z.; Norazian, M. H.; Rashidi, O. Identification of carotenoid composition in selected ‘ulam’ or traditional vegetables in Malaysia. Int. Food. Res. J. 2012, 19 (2), 527−530. (18) Sangeetha, R. K.; Baskaran, V. Carotenoid Composition and Retinol Equivalent in Plants of Nutritional and Medicinal Importance: Efficacy of β-carotene from Chenopodium album in Retinol-deficient Rats. Food Chem. 2010, 119 (4), 1584−1590. (19) Mamatha, B. S.; Sangeetha, R. K.; Baskaran, V. Provitamin-A and Xanthophyll Carotenoids in Vegetables and Food Grains of Nutritional and Medicinal Importance. Int. J. Food Sci. Technol. 2011, 46 (2), 315−323.

6. CONCLUSION Carotenoids are not thermostable compounds and, hence, liable to heat, light, and oxygen which could cause degradation and isomerization. Consequently, the laboratory environment should be controlled. However, encapsulation could also help curb/minimize the interaction between extracted carotenoids and environmental factors. Therefore, we recommend rapid encapsulation of freeze-dried carotenoids immediately after extractions. With respect to methods of extraction, SC-CO2 and enzyme-based extraction showed the best results in regard to both product and process safety on the environment. Coupling two or more methods could also enhance yield and reduce cost as well as time of extraction in some cases. In addition, response surface methodology could be applied for optimizing extraction parameters for better yields. For the enzymatic method of extraction, knowledge about the cell structure of the particular plant material is very important. Vegetable oils could also replace chemical solvents. Heavy smokers and alcoholics should either minimize/quit when they are on carotenoid supplements to avoid being exposed to the risk of chronic diseases mentioned above. However, this could also ensure efficient metabolism of carotenoids to confer health benefits.

■

REFERENCES

AUTHOR INFORMATION

Corresponding Author

*Telephone: +79817511640. E-mail: [email protected]; [email protected]. ORCID

Parise Adadi: 0000-0003-4724-9463 Notes

The authors declare no competing financial interest.

■

ABBREVIATIONS SC-CO2, supercritical carbon dioxide; UAE, Ultrasonic assisted extraction; MAE, Microwave-assisted extraction; MASE, microwave-assisted solvent extraction; MSFE, microwave solvent-free extraction; SFE, Supercritical fluid extraction; COSE, conventional organic solvent extraction; UV−vis, Ultraviolet−visible spectrophotometry; HPLC, high-performance liquid chromatography; HPTLC, high-performance thin layer chromatog5939


Review

Journal of Agricultural and Food Chemistry (20) Rodrigo, M. J.; Marcos, J. F.; Zacarias, L. Biochemical and Molecular Analysis of Carotenoid Biosynthesis in Flavedo of Orange (Citrus sinensis L.) During Fruit Development and Maturation. J. Agric. Food Chem. 2004, 52 (22), 6724−6731. (21) Mamatha, B. S.; Arunkumar, R.; Baskaran, V. Effect of Processing on Major Carotenoid Levels in Corn (Zea mays) and Selected Vegetables: Bioavailability of Lutein and Zeaxanthin from Processed Corn in Mice. Food Bioprocess Technol. 2012, 5, 1355−1363. (22) Lakshminarayana, R.; Raju, M.; Krishnakantha, T. P.; Baskaran, V. Enhanced Lutein Bioavailability by Lyso-phosphatidylcholine in Rats. Mol. Cell. Biochem. 2006, 281 (1−2), 103−113. (23) Mamatha, B. S.; Baskaran, V. Effect of Micellar Lipids, Dietary Fiber and β-carotene on Lutein Bioavailability in Aged Rats with Lutein Deficiency. Nutrition 2011, 27 (9), 960−966. (24) Nidhi, B.; Mamatha, B. S.; Baskaran, V. Olive Oil Improves the Intestinal Absorption and Bioavailability of Lutein in Lutein-Deficient Mice. Eur. J. Nutr. 2014, 53 (1), 117−126. (25) Yamaguchi, M. β-cryptoxanthin and Bone Metabolism: The Preventive Role in Osteoporosis. J. Health Sci. 2008, 54 (4), 356−369. (26) Yamaguchi, M.; Igarashi, A.; Uchiyama, S.; Morita, S.; Sugawara, K.; Sumida, T. Prolonged Intake of Juice (Citrus Unshiu) Reinforced with β-cryptoxanthin Has an Effect on Circulating Bone Biochemical Markers in Normal Individuals. J. Health Sci. 2004, 50 (6), 619−624. (27) Sugiura, M.; Kato, M.; Matsumoto, H.; Nagao, A.; Yano, M. Serum Concentration of b-cryptoxanthin in Japan Reflects the Frequency of Satsuma Mandarin (Citrus unshiu March.) Consumption. J. Health Sci. 2002, 48 (4), 350−353. (28) Britton, G.; Khachik, F. Carotenoid in Food. In Carotenoids: Nutrition and Health; Britton, G.; Liaaen-Jensen, F.; Pfander, H.; Eds.; Birkhauser Verlag Basel, 2009; 431 pp. (29) Raju, M.; Varakumar, S.; Lakshminarayana, R.; Krishnakantha, T. P.; Baskaran, V. Carotenoid Composition and Vitamin A Activity of Medicinally Important Green Leafy Vegetables. Food Chem. 2007, 101 (4), 1598−1605. (30) Lakshminarayana, R.; Raju, M.; Krishnakantha, T. P.; Baskaran, V. Determination of Major Carotenoids in Few Indian Leafy Vegetables by High-Performance Liquid Chromatography. J. Agric. Food Chem. 2005, 53 (8), 2838−2842. (31) Stephen, N.; Gayathri, R.; Niranjana, Y.; Prasad, K. Y.; Das, A. K.; Baskaran, V.; Ganesan, P. Carotenoids: types, sources, and biosynthesis. In Plant Secondary Metabolites: Stimulation, Extraction, and Utilization; Siddiqui, M. W.; Bansal, V.; Prasad, K., Eds.; Apple Academic Press: NJ, 2017, 281 pp. (32) Dharmananda, S. Sea buckthorn. (http://www.itmonline.org/ arts/seabuckthorn.htm) (24/02/2018). (33) Sommerburg, O.; Keunen, J. E. E.; Bird, A. C.; van Kuijk, F. J. G. M. Fruits and Vegetables that are Sources for Lutein and zeaxanthin: The Macular Pigment in Human Eyes. Br. J. Ophthalmol. 1998, 82 (8), 907−910. (34) Sajilata, M. G.; Singhal, R. S.; Kamat, M. Y. The Carotenoid Pigment ZeaxanthinA Review. Compr. Rev. Food Sci. Food Saf. 2008, 7 (1), 29−49. (35) Fordham, I. M.; Clevidence, B. A.; Wiley, E. R.; Zimmerman, R. H. Fruit of autumn olive: a rich source of lycopene. HortScience 2001, 36 (6), 1136−1137. (36) de Ancos, B.; Gonzalez, E.; Cano, M. P. Effect of high-pressure treatment on the carotenoid composition and the radical scavenging activity of persimmon fruit purees. J. Agric. Food Chem. 2000, 48 (8), 3542−3548. (37) Porcu, O. M.; Rodriguez-Amaya, D. B. Variation in the carotenoid composition of the lycopene-rich Brazilian fruit Eugenia uniflora L. Plant Foods Hum. Nutr. 2008, 63 (4), 195−199. (38) Vkool. List of best lycopene rich foods - top 13 choices. (http:// vkool.com/lycopene-rich-foods/) (14/05/2018). (39) Mayer-Miebach, E.; Spieß, W. E. L. Influence of cold storage and blanching on the carotenoid content of Kintoki carrots. J. Food. Eng, 2003 carotenoid content of Kintoki carrots. J. Food Eng. 2003, 56 (2−3), 211−213.

(40) Mayer-Miebach, E.; Behsnilian, D.; Regier, M.; Schuchmann, H. P. Thermal processing of carrots: Lycopene stability and isomerisation with regard to antioxidant potential. Food Res. Int. 2005, 38 (8−9), 1103−1108. (41) Tran, T.; Raymundo, L. C. Biosynthesis of carotenoids in bitter melon at high temperature. Phytochemistry 1999, 52, 275−280. (42) Bruno, A.; Durante, M.; Marrese, P. P.; Migoni, D.; Laus, M. N.; Pace, E.; Pastore, D.; Mita, G.; Piro, G.; Lenucci, M. S. Shades of red: comparative study on supercritical CO2 extraction of lycopene-rich oleoresins from gac, tomato and watermelon fruits and effect of the -cyclodextrin clathrated extracts on cultured lung adenocarcinoma cells’ viability. J. Food Compos. Anal. 2018, 65, 23−32. (43) Tinoi, J.; Rakariyatham, N.; Deming, R. L. Determination of Major Carotenoid Constituents in Petal Extracts of Eight Selected Flowering Plants in the North of Thailand. Chiang Mai. J. Sci. 2006, 33 (2), 327−334. (44) Jaswir, I.; Noviendri, D.; Hasrini, R. F.; Octavianti, F. Carotenoids: Sources, Medicinal Properties and Their Application in Food and Nutraceutical Industry. J. Med. Plants Res. 2011, 5 (33), 7119−7131. (45) Tanaka, T.; Shnimizu, M.; Moriwaki, H. Cancer Chemoprevention by Carotenoids. Molecules 2012, 17 (3), 3202−3242. (46) Bakshi, H.; Sam, S.; Rozati, R.; Sultan, P.; Islam, T.; Rathore, B.; Lone, Z.; Sharma, M.; Triphati, J.; Saxena, R. C. DNA Fragmentation and Cell Cycle Arrest: A Hallmark of Apoptosis Induced by Crocin from Kashmiri Saffron in a Human Pancreatic Cancer Cell Line. Asian. Pac. J. Cancer. Prev. 2010, 11 (3), 675−679. (47) Cazzonelli, C. I. Carotenoids in Nature: Insights from Plants and Beyond. Funct. Plant Biol. 2011, 38 (11), 833−847. (48) Galasso, C.; Corinaldesi, C.; Sansone, C. Carotenoids from Marine Organisms: Biological Functions and Industrial Applications. Antioxidants 2017, 6 (4), 96. (49) Ganesan, P.; Matsubara, K.; Ohkubo, T.; Tanaka, Y.; Noda, K.; Sugawara, T.; Hirata, T. Anti-Angiogenic Effect of Siphonaxanthin from Green Alga. Phytomedicine 2010, 17, 1140−1144. (50) Ganesan, P.; Matsubara, K.; Sugawara, T.; Hirata, T. Marine Algal Carotenoids Inhibit Angiogenesis by Down-Regulating FGF-2mediated Intracellular Signals in Vascular Endothelial Cells. Mol. Cell. Biochem. 2013, 380 (14), 1−9. (51) Burczyk, J. Cell Wall Carotenoids in Green Algae Which Form Sporopollenins. Phytochemistry 1986, 26 (1), 121−128. (52) Takaichi, S. Carotenoids in Algae: Distributions, Biosyntheses and Functions. Mar. Drugs 2011, 9 (6), 1101−1118. (53) Del Campo, J.; Rodriguez, H.; Moreno, J.; Vargas, M.; Rivas, J.; Guerrero, M. Accumulation of Astaxanthin and Lutein in. Appl. Microbiol. Biotechnol. 2004, 64 (6), 848−854. (54) Hagen, C.; Grünewald, K.; Schmidt, S.; Müller, J. Accumulation of Secondary Carotenoids in Flagellates of Haematococcus pluvialis (Chlorophyta) Is Accompanied by an Increase in per Unit Chlorophyll Productivity of Photosynthesis. Eur. J. Phycol. 2000, 35 (1), 75−82. (55) Grabowski, B.; Cunningham, F. X.; Gantt, E. Chlorophyll and Carotenoid Binding in a Simple Red Algal Light-Harvesting Complex Crosses Phylogenetic Lines. Proc. Natl. Acad. Sci. U. S. A. 2001, 98 (5), 2911−2916. (56) Schubert, N.; García-Mendoza, E.; Enríquez, S. Is the Photoacclimatory Response of Rhodophyta Conditioned by the Species Carotenoid Profile? Limnol. Oceanogr. 2011, 56 (6), 2347−2361. (57) Garcia-Mendoza, E.; Ocampo-Alvarez, H. Photoprotection in the Brown Alga Macrocystis pyrifera: Evolutionary Implications. J. Photochem. Photobiol., B 2011, 104 (1−2), 377−385. (58) Takaichi, S.; Mirauro, M. Distribution and Geometric Isomerism of Neoxanthin in Oxygenic Phototrophs: 9-cis, a Sole Molecular form. Plant Cell Physiol. 1998, 39 (9), 968−977. (59) Terasaki, M.; Bhaskar, N.; Kamokawa, H.; Nomura, M.; Stephen, M. N.; Kawagoe, C.; Hosokawa, M. Miyashita. K. Carotenoid Profile of Edible Japanese Seaweeds: An Improved HPLC Method for Separation of major Carotenoids. J. Aquat. Food Prod. Technol. 2012, 21 (5), 468−479. 5940


Review

Journal of Agricultural and Food Chemistry (60) Noviendri, D.; Jaswir, I.; Salleh, H. M.; Taher, M.; Miyashita, K.; Ramli, N. Fucoxanthin Extraction and Fatty Acid Analysis of Sargassum binderi and S. duplicatum. J. Medic. Plant. Res. 2011, 11 (5), 2405− 2412. (61) Yoshii, Y.; Takaichi, S.; Maoka, T.; Suda, S.; Sekiguchi, H.; Nakayama, T.; Inouye, I. Variation of Siphonaxanthin Series among the Genus Nephroselmis (Prasinophyceae, Chlorophyta), Including a Novel Primary Methoxy Carotenoid. J. Phycol. 2005, 41 (4), 827−834. (62) Sugawara, T.; Ganesan, P.; Li, Z.; Manabe, Y.; Hirata, T. Siphonaxanthin, a Green Algal Carotenoid, as a Novel Functional Compound. Mar. Drugs 2014, 12 (6), 3660−3668. (63) Short, F.; Carruthers, T.; Dennison, W.; Waycott, M. Global seagrass distribution and diversity: A bioregional model. J. Exp. Mar. Biol. Ecol. 2007, 350 (1−2), 3−20. (64) Hemminga, M. A.; Duarte, C. M. Seagrass Ecology; Cambridge University Press: Cambridge, 2000; 298 pp. (65) Casazza, G.; Mazzella, L. Photosynthetic pigment composition of marine angiosperms: Preliminary characterization of Mediterranean seagrasses. Bull. Mar. Sci. 2002, 71 (3), 1171−1181. (66) Silva, J.; Barrote, I.; Costa, M. M.; Albano, S.; Santos, R. Physiological responses of Zostera marina and Cymodocea nodosa to light-limitation stress. PLoS One 2013, 8 (11), e81058. (67) Cardoso, L. A. C.; Karp, S. G.; Vendruscolo, F.; Kanno, K. Y. F.; Zoz, L. I. C.; Carvalho, J. C. Biotechnological Production of Carotenoids and Their Applications in Food and Pharmaceutical Products; InTechOpen: London, 2017. (68) Maoka, T. Carotenoids in Marine Animals- a review. Mar. Drugs 2011, 9 (2), 278−293. (69) Maoka, T.; Mochida, K.; Kozuka, M.; Ito, Y.; Fujiwara, Y.; Hashimoto, K.; Nishino, H. Cancer chemopreventive activity of carotenoids in the fruits of red paprika Capsicum annuum L. Cancer Lett. 2001, 172 (2), 103−109. (70) Bjerkeng, B. Carotenoids in aquaculture: Fish and crustaceans. Carotenoids 2008, 4, 237−254. (71) Tushima, M.; Maoka, T.; Matsuno, T. Comparative biochemical studies of carotenoids in marine invertebrates. The first positive identification of ε,ε-carotene derivatives and isolation of two new carotenoids from chitons. Comp. Biochem. Physiol. 1989, 93 (3), 665− 671. (72) Yamashita, E.; Matsuno, T. A new apocarotenoid from the sea hareAplysia kurodai. Comp. Biochem. Physiol 1990, 96 (3), 465−470. (73) Liaaen-Jensen, S. Carotenoids in Food Chain. In Carotenoids: Biosynthesis and Metabolism; Britton, G.; Liaaen-Jensen, S.; Pfander, H.; Eds.; Birkhäuser: Basel, 1998; Vol. 3; 411 pp. (74) Maoka, T. Recent progress in structural studies of carotenoids in animals and plants. Arch. Biochem. Biophys. 2009, 483 (2), 191−195. (75) Matsuno, T. Animal carotenoids. In Carotenoids Chemistry and Biology; Krinsky, N. I.; Mathews-Roth, M. M.; Taylor, R. F.; Eds.; Plenum Press: New York, 1989; 390 pp. (76) Matsuno, T. Aquatic animal carotenoids. Fish. Sci. 2001, 67 (5), 771−783. (77) Maoka, T.; Yokoi, S.; Matsuno, T. Comparative biochemical studies of carotenoids in nine species of Cephalopoda. Comp. Biochem. Physiol 1989, 92 (2), 247−250. (78) Slifka, K. A.; Bowen, P. E.; Stacewicz-Sapuntzakis, M.; Crissey, S. D. A survey of serum and dietary carotenoids in captive wild animals. J. Nutr. 1999, 129 (2), 380−390. (79) Liaaen-Jensen, S. Marine carotenoidsSelected topics. New J. Chem. 1990, 14, 747−759. (80) Matsuno, T.; Hirao, S. Marine carotenoids. In: Marine Biogenic Lipids, Fats, and Oils; Ackman, R. G., Ed.; CRC Press: Boca Raton, FL, 1989; Vol. 1, 472 pp. (81) Lampila, L. E.; Wallen, S. E.; Bullerman, L. B. A Review of Factors Affecting Biosynthesis of Carotenoids by the Order Mucorales. Mycopathologia 1985, 90 (2), 65−80. (82) Finkelstein, M.; Haung, C. C.; Byng, G. S.; Tsau, B.-R.; Leach, J. Blakeslea trispora Mated Culture Capable of Increased β-carotene Production, U.S. Patent 5422247 A, June 6, 1995.

(83) Frengova, G. I.; Beshkova, D. M. Carotenoids from Rhodotorula and Phaffia: Yeasts of Biotechnological Importance. J. Ind. Microbiol. Biotechnol. 2009, 36 (2), 163−180. (84) Nelis, H. J.; De Leenheer, A. P. Microbial Sources of Carotenoid Pigments Used in Foods and Feeds. J. Appl. Bacteriol. 1991, 70 (3), 181−191. (85) Wang, H. B.; Xu, R. G.; Yu, L. J.; Luo, J.; Zhang, L. W.; Huang, X. Y.; Zou, W. A.; Zhao, Q.; Lu, M. B. Improved Beta-carotene and Lycopene Production by Blakeslea trispora with Ultrasonic Treatment in Submerged Fermentation. Z. Naturforsch., C: J. Biosci. 2014, 69 (5− 6), 237−244. (86) Xu, F.; Yuan, Q.-P.; Zhu, Y. Improved Production of Lycopene and β-carotene by Blakeslea trispora with Oxygen-Vectors. Process Biochem. 2007, 42 (2), 289−293. (87) Choudhari, S. M.; Ananthanarayan, L.; Singhal, S. R. Use of Metabolic Stimulators and Inhibitors for Enhanced Production of βcarotene and Lycopene by Blakeslea trispora NRRL 2895 and 2896. Bioresour. Technol. 2008, 99 (8), 3166−3173. (88) Andrewes, A. G.; Phaff, J. H.; Starr, P. M. Carotenoids of Phaf f ia rhodozyma, a Red-Pigmented Fermenting Yeast. Phytochemistry 1976, 15 (6), 1003−1007. (89) Johnson, E. A.; Lewis, M. J. Astaxanthin Formation by the Yeast. J. Gen. Microbiol. 1979, 115, 173−183. (90) Johnson, E. A. Phaffia rhodozyma: Colorful Odyssey. Int. Microbiol. 2003, 6 (3), 169−174. (91) Bhosale, P.; Bernstein, P. S. Microbial Xanthophylls. Appl. Microbiol. Biotechnol. 2005, 68 (4), 445−455. (92) Dominguez-Bocanegra, A. R.; Ponce-Noyola, T.; Torres-Munoz, J. A. Astaxanthin Production by Phaf f ia rhodozyma and Haematococcus pluvialis: A Comparative Study. Appl. Microbiol. Biotechnol. 2007, 75 (4), 783−791. (93) Zheng, Y.-G.; Hu, Z.-C.; Wang, Z.; Shen, Y. C. Large-Scale Production of Astaxanthin by Xanthophyllomyces dendrorhous. Food Bioprod. Process. 2006, 84 (2), 164−166. (94) Rodriguez-Saiz, M.; Dela Fuente, J. L.; Barredo, J. L. Xanthophyllomyces dendrorhous for the Industrial Production of Astaxanthin. Appl. Microbiol. Biotechnol. 2010, 88 (3), 645−658. (95) Schmidt, I.; Schewe, H.; Gassel, S.; Jin, C.; Buckingham, J.; Humbelin, M.; Sandmann, G.; Schrader, J. Biotechnological Production of astaxanthin with Phaf f ia rhodozyma/ Xanthophyllomyces dendrorhous. Appl. Microbiol. Biotechnol. 2011, 89 (3), 555− 571. (96) Araya-Garay, J. M.; Feijoo-Siota, L.; Rosa-dos-Santos, F.; VeigaCrespo, P.; Villa, T. G. Construction of new Pichia pastoris X-33 strains for production of lycopene and β-carotene. Appl. Microbiol. Biotechnol. 2012, 93 (6), 2483−2492. (97) Araya-Garay, J. M.; Ageitos, J. M.; Vallejo, J. A.; Veiga-Crespo, P.; Sánchez-Pérez, A.; Villa, T. G. Construction of a novel Pichia pastoris strain for production of xanthophylls. AMB Express 2012, 2 (1), 24. (98) Miura, Y.; Kondo, K.; Saito, T.; Shimada, H.; Fraser, P. D.; Misawa, N. Production of the Carotenoids Lycopene, β-Carotene, and Astaxanthin in the Food Yeast Candida utilis. Appl. Environ. Microbiol. 1998, 64 (4), 1226−1229. (99) Verwaal, R.; Wang, J.; Meijnen, J. P.; Visser, H.; Sandmann, G.; van den Berg, J. A.; van Ooyen, A. J. High-level Production of Betacarotene in Saccharomyces cerevisiae by Successive Transformation with Carotenogenic Genes from Xanthophyllomyces dendrorhous. Appl. Environ. Microbiol. 2007, 73 (13), 4342−4350. (100) Zhang, Y.; Chen, H.; Navarro, E.; Lopez-Garcıa, S.; Chen, Y. Q.; Zhang, H.; Chen, W.; Garre, V. Generation of lycopeneoverproducing strains of the fungus Mucor circinelloides reveals important aspects of lycopene formation and accumulation. Biotechnol. Lett. 2017, 39 (3), 439−446. (101) Davoli, P.; Weber, R. W. S. Carotenoid Pigments from the Red Mirror Yeast, Sporobolomyces Roseus. Mycologist 2002, 16 (3), 102− 108. 5941


Review


(122) Tian, B.; Hua, Y. Carotenoid Biosynthesis in Extremophilic Deincoccus−Thermos Bacteria. Trends Microbiol. 2010, 18 (11), 512− 520. (123) Osawa, O.; Harada, H.; Choi, S. K.; Misawa, N.; Shindo, K. Production of Caloxanthin 3′-β-D-glucoside, zeaxanthin 3,3′-β-Ddiglucoside, and Nostoxanthin in a Recombinant Escherichia coli Expressing System Harboring Seven Carotenoid Biosynthesis Genes, Including Crt X and Crt G. Phytochemistry 2011, 72 (8), 711−716. (124) Ide, T.; Hoya, M.; Tanaka, T.; Harayama, S. Enhanced Production of Astaxanthin in Paracoccus sp. strain N-81106 by using Random Mutagenesis and Genetic Engineering. Biochem. Eng. J. 2012, 65, 37−43. (125) Misawa, N.; Nakagawa, M.; Kobayashi, K.; Yamano, S.; Izawa, Y.; Nakamura, K.; Harashima, K. Elucidation of the Erwiniauredovora Carotenoid Biosynthetic Pathway by Functional Analysis of Gene Products Expressed in. J. Bacteriol. 1990, 172 (12), 6704−6712. (126) Cunningham, F. X.; Chamovitz, D.; Misawa, N.; Gantt, E.; Hirschberg, J. Cloning and Functional Expression in Escherichia coli of a Cyanobacterial Gene for Lycopene Cyclase, the Enzyme that Catalyzes the Biosynthesis of β-carotene. FEBS Lett. 1993, 328 (1−2), 130−127. (127) Ruther, A.; Misawa, N.; Boger, P.; Sandmann, G. Production of Zeaxanthin in Escherichia coli Transformed with Different Carotenogenic Plasmids. Appl. Microbiol. Biotechnol. 1997, 48 (2), 162−167. (128) Sandmann, G. Combinatorial Biosynthesis of Carotenoids in a Heterologous Host: A Powerful Approach for the Biosynthesis of Novel Structures. ChemBioChem 2002, 3 (7), 629−635. (129) Alper, H.; Miyaoku, K.; Stephanopoulos, G. Characterization of Lycopene-Overproducing E. coli Strains in High Cell Density Fermentations. Appl. Microbiol. Biotechnol. 2006, 72 (5), 968−974. (130) Yoon, S. H.; Lee, Y. M.; Kim, J. E.; Lee, S. H.; Lee, J. H.; Kim, J. Y.; Jung, K. H.; Shin, Y. C.; Keasling, J. D.; Kim, S. W. Enhanced Lycopene Production in Escherichia coli Engineered to Synthesize Isopentenyl Diphosphate and Dimethylallyl Diphosphate from Mevalonate. Biotechnol. Bioeng. 2006, 94 (6), 1025−1032. (131) Yoon, S. H.; Kim, J. E.; Lee, S. H.; Park, H. M.; Choi, M. S.; Kim, J. Y.; Lee, S. H.; Shin, Y. C.; Keasling, J. D.; Kim, S. W. Engineering the Lycopene Synthetic Pathway in E. coli by Comparison of the Carotenoid Genes of Pantoea agglomerans and Pantoea ananatis. Appl. Microbiol. Biotechnol. 2007, 74 (1), 131−139. (132) Yuan, L. Z.; Rouviere, P. E.; Larossa, R. A.; Suh, W. Chromosomal Promoter Replacement of the Isoprenoid Pathway for Enhancing Carotenoid Production in. Metab. Eng. 2006, 8 (1), 79−90. (133) Hirschberg, J.; Harker, M. Carotenoid-Producing Bacterial Species and Process for Production of Carotenoids using Same. U.S. Patent 5,935,808. Publication date: August 10, 1999. (134) Tatsuzawa, H.; Maruyama, T.; Misawa, N.; Fujimori, K.; Nakano, M. Quenching of Singlet Oxygen by Carotenoids Produced in Escherichia coli-attenuation of Singlet Oxygen-Mediated Bacterial Killing by Carotenoids. FEBS Lett. 2000, 484 (3), 280−284. (135) Shepherd, D.; Dasek, J.; Suzanne, M.; Carels, C. Production of Zeaxanthin. US Patent 3,951-743. Publication date: April 20, 1976. (136) Hümbelin, M.; Thomas, A.; Lin, J.; Jore, J.; Berry, A. Genetics of Isoprenoid Biosynthesis in. Gene 2002, 297 (1−2), 129−139. (137) Asker, D.; Beppu, T.; Ueda, K. Sphingomonas jaspsi sp. A Novel Carotenoid-Producing Bacterium Isolated from Misasa, Tottori, Japan. Int. J. Syst. Evol. Microbiol. 2007, 57 (7), 1435−1441. (138) Somporn, T.; Syarm, K.; Sutha, W.; Kohei, O. Application of a New Red Carotenoid Pigment-Producing Bacterium, Enterobacter sp. P41, as feed Supplement for Chicken. Afr. J. Biotechnol. 2013, 12 (1), 64−69. (139) Garrido-Fernández, J.; Maldonado-Barragán, A.; CaballeroGuerrero, B.; Hornero-Méndez, D.; Ruiz-Barba, J. L. Carotenoid Production in Lactobacillus plantarum. Int. J. Food Microbiol. 2010, 140 (1), 34−39. (140) Liu, G. Y.; Essex, A.; Buchanan, J. T.; Datta, V.; Hoffman, H. M.; Bastian, J. F.; Fierer, J.; Nizet, V. Staphylococcus aureus Golden Pigment Impairs Neutrophil Killing and Promotes Virulence Through Its Antioxidant Activity. J. Exp. Med. 2005, 202 (2), 209−215.

(102) Mata-Gómez, L. C.; Montañez, J. C.; Méndez-Zavala, A.; Aguilar, C. N. Biotechnological production of carotenoids by yeasts: an overview. Microb. Cell Fact. 2014, 13 (1), 12. (103) Valduga, E.; Tatsch, P.; Vanzo, L.; Rauber, F.; Di Luccio, M.; Treichel, H. Assessment of hydrolysis of cheese whey and use of hydrolysate for bioproduction of carotenoids by Sporidiobolus salmonicolor CBS 2636. J. Sci. Food Agric. 2009, 89 (6), 1060−1065. (104) Takaichi, S.; Mochimaru, M. Carotenoids and Carotenogenesis in Cyanobacteria: Unique Ketocarotenoids and Carotenoid Glycosides. Cell. Mol. Life Sci. 2007, 64 (19−20), 2607−2619. (105) Costa, M.; Costa-Rodrigues, J.; Fernandes, M. H.; Barros, P.; Vasconcelos, V.; Martins, R. Marine Cyanobacteria Compounds with Anticancer Properties: A Review on the Implication of Apoptosis. Mar. Drugs 2012, 10 (12), 2181−2207. (106) Prasanna, R.; Sood, A.; Jaiswal, P.; Nayak, S.; Gupta, V.; Chaudhary, V.; Joshi, M.; Natarajan, M. Rediscovering Cyanobacteria as Valuable Sources of Bioactive Compounds (Review). Appl. Biochem. Microbiol. 2010, 46 (2), 119−134. (107) Gombos, Z.; Vigh, L. Primary Role of the Cytoplasmic Membrane in Thermal Acclimation Evidenced in Nitrate-Starved Cells of the Blue-Green Alga. Plant Physiol. 1986, 80 (2), 415−419. (108) Cheng, Q. Structural Diversity and Functional Novelty of New Carotenoid Biosynthesis Genes. J. Ind. Microbiol. Biotechnol. 2006, 33 (7), 552−559. (109) Kelman, D.; Ben-Amotz, A.; Berman-Frank, I. Carotenoids Provide the Major Antioxidant Defense in the Globally Significant N2fixing Marine Cyanobacterium. Environ. Microbiol. 2009, 11 (7), 1897−1908. (110) Prasanna, R.; Pabby, A.; Singh, P. K. Effect of Glucose and Light−Dark Environment on Pigmentation Profiles in the. Folia Microbiol. 2004, 49 (1), 26−30. (111) Goodwin, T. W. Carotenoids in fungi and non-photosynthetic bacteria. Prog. Ind. Microbiol. 1972, 11, 29−88. (112) Goodwin, T. W. In Handbook of Microbiology. Laskin, I. A.; Lechevalier, H. A., Eds.; CRC Press: Cleveland, OH, 1978; Vol. 3, 75− 83. (113) Baxter, R. M. Carotenoid Pigments of Halophilic Bacteria. Can. J. Microbiol. 1960, 6, 417−424. (114) Asker, D.; Ohta, Y. Production of Canthaxanthin by Extremely Halophilic Bacteria. J. Biosci. Bioeng. 1999, 88 (6), 617−621. (115) Dufosse, L.; Galaup, P.; Yaron, A.; Arad, S. M.; Blanc, P.; Chidambara Murthy, K. N.; Ravishankar, G. A. Microorganisms and Microalgae as Sources of Pigments for food use: A Scientific Oddity or an Industrial Reality? Trends Food Sci. Technol. 2005, 16 (9), 389−406. (116) Lutnaes, B. F.; Strand, A.; Pétursdóttir, S. K.; Liaaen-Jensen, S. Carotenoids of Thermophilicbacteria Rhodothermusmarinus from Submarine Icelandic Hot Springs. Biochem. Syst. Ecol. 2004, 32 (5), 455−468. (117) Das, A.; Yoon, S. H.; Lee, S. H.; Kim, J. Y.; Oh, D. K.; Kim, S. W. An Update on Microbial Carotenoid Production: Application of Recent Metabolic Engineering Tools. Appl. Microbiol. Biotechnol. 2007, 77 (3), 505−512. (118) Yoon, S. H.; Lee, S. H.; Das, A.; Ryu, H. K.; Jang, H. J.; Kim, J. Y.; Oh, D. K.; Keasling, J. D.; Kim, S. W. Combinatorial Expression of Bacterial whole Mevalonate Pathway for the Production of β-carotene in. J. Biotechnol. 2009, 140 (3−4), 218−226. (119) Wang, B.; Lin, L.; Lu, L.; Chen, W. Optimization of β-carotene Production by a Newly Isolated Serratia marcescens Strain. Electron. J. Biotechnol. 2012, 15 (6), 1−3. (120) Naziri, D.; Hamidi, M.; Hassanzadeh, S.; Tarhriz, V.; Maleki Zanjani, B.; Nazemyieh, H.; Hejazi, M. A.; Hejazi, M. S. Analysis of Carotenoid Production by Halorubrum sp. TBZ126: An Extremely Halophilic Archeon from Urmia Lake. Adv. Pharm. Bull. 2014, 4 (1), 61−67. (121) Stafsnes, M. H.; Josefsen, K. D.; Kildahl-Andersen, G.; Valla, S.; Ellingsen, T. E.; Bruheim, P. Isolation and Characterization of Marine Pigmented Bacteria from Norwegian Coastal Waters and Screening for Carotenoids with UVA-Blue Light Absorbing Properties. J. Microbiol. 2010, 48 (1), 16−23. 5942


Review

Journal of Agricultural and Food Chemistry (141) Clauditz, A.; Resch, A.; Wieland, K.-P.; Peschel, A.; Gotz, F. Staphyloxanthin Plays a Role in the Fitness of Staphylococcus aureus and its Ability to Cope with Oxidative Stress. Infect. Immun. 2006, 74 (8), 4950−4953. (142) Yokoyama, A.; Sandmann, G.; Hoshino, T.; Adachi, K.; Sakai, M.; Shizuri, Y. Thermozeaxanthins, New Carotenoid-Glycoside-Esters from Thermophilic Eubacterium. Tetrahedron Lett. 1995, 36 (27), 4901−4904. (143) Tian, B.; Hua, Y. Carotenoid Biosynthesis in Extremophilic Deincoccus−Thermos Bacteria. Trends Microbiol. 2010, 18 (11), 512− 520. (144) Stafsnes, M. H.; Josefsen, K. D.; Kildahl-Andersen, G.; Valla, S.; Ellingsen, T. E.; Bruheim, P. Isolation Characterization of Marine Pigmented Bacteria from Norwegian Coastal Waters and Screening for Carotenoids with UVA-Blue Light Absorbing Properties. J. Microbiol. 2010, 48 (1), 16−23. (145) Walter, M. H.; Strack, D. Carotenoids and their cleavage products: biosynthesis and functions. Nat. Prod. Rep. 2011, 28 (4), 663−692. (146) Sharoni, Y.; Linnewiel-Hermoni, K.; Khanin, M.; Salman, H.; Veprik, A.; Danilenko, M.; Levy, J. Carotenoids and apocarotenoids in cellular signaling related to cancer: a review. Mol. Nutr. Food Res. 2012, 56 (2), 259−269. (147) Sasaki, H.; Morota, T.; Nishimura, H.; Ogino, T.; Katsuhara, T.; Sugama, K.; Chin, M.; Mitsuhashi, H. Norcarotenoids of Rehmannia glutinosa var. Hueichingensis. Phytochemistry 1991, 30 (6), 1997−2001. (148) Barua, A. B.; Furr, H. C.; Olson, J. A.; Van Breemen, R. B. Vitamin A and carotenoids. In Modern Chromatographic Analysis of Vitamins, 3rd. ed.; De Leenheer, A. P.; Lambert, W. E.; Van Bocxlaer, J. F., Eds.; Marcel Dekker: New York, 2000; 616 pp. (149) Albermann, C.; Beuttler, H. Synthesis of β-Carotene and Other Important Carotenoids with Bacteria. In Industrial Biotechnology of Vitamins, Biopigments, and Antioxidants; Vandamme, E. J.; Revuelta, J. L., Eds.; Wiley-VCH: Weinheim, Germany, 2016; 548 pp. (150) Maoka, T.; Fujiwara, Y.; Hashimoto, K.; Akimoto, N. 5Hydroxy-seco-carotenoids from Pittosporum tobira. Phytochemistry 2006, 67 (19), 2120−2125. (151) Rohmer, M.; Knani, M.; Simonin, P.; Sutter, D.; Sahm, H. Isoprenoid Biosynthesis in Bacteria: A Noval Pathway for Early Steps Leading to Isopentenyl Diphosphate. Biochem. J. 1993, 295 (2), 517− 524. (152) Lichtenthaler, H. K.; Rohmer, M.; Schwender, J. Two Independent Biochemical Pathway for Isopentenyl Di Phosphate and Isoprenoid Biosynthesis in Higher Plants. Physiol. Plant. 1997, 101 (3), 643−652. (153) Rodriguez-Concepcion, M.; Boronat, A. Elucidation of the Methylerythritol Phosphate Pathway for Isoprenoid Biosynthesis in Bacteria and Plastids. A metabolic Milestones Achieved through Genomics. Plant Physiol. 2002, 130 (3), 1079−1089. (154) Cazzonelli, C. I.; Pogson, B. J. Source to sink: regulation of carotenoid biosynthesis in plants. Trends Plant Sci. 2010, 15 (5), 266− 274. (155) Cordoba, E.; Salmi, M.; León, P. Unravelling the regulatory mechanisms that modulate the MEP pathway in higher plants. J. Exp. Bot. 2009, 60 (10), 2933−2943. (156) Hunter, W. N. The non-mevalonate pathway of isoprenoid precursor biosynthesis. J. Biol. Chem. 2007, 282 (30), 21573−21577. (157) Ganjewala, D.; Kumar, S.; Luthra, R. An account of cloned genes of methylerythritol-4-phosphate pathway of isoprenoid biosynthesis in plants. Curr. Issues Mol. Biol. 2009, 11 (1), 35−45. (158) Nishida, Y.; Adachi, K.; Kasai, H.; Shizuri, Y.; Shindo, K.; Sawabe, A.; Komemushi, S.; Miki, W.; Misawa, N. Elucidation of a Carotenoid Biosynthesis Gene Cluster Encoding a Novel Enzyme, 2,2hydroxylase, from Brevundimonas sp. strain SD212 and Combinatorial Biosynthesis of New or Rare Xanthophylls. Appl. Environ. Microbiol. 2005, 71 (8), 4286−4296. (159) Rodriguez-Amaya, D. B. A guide to carotenoid analysis in foods; ILSI-International Life Sciences Institute: Washington, D. C., 2001.

(160) Giraud, E.; Hannibal, L.; Fardoux, J.; Jaubert, M.; Dreyfus, B.; Sturgis, J. N.; Vermeqlio, A. Two Distinct crt Gene Cluster for Two Different Functional Classes of Carotenoid in. J. Biol. Chem. 2004, 279 (15), 15076−15083. (161) Frigaard, N. U.; Maresca, J. A.; Yunker, C. E.; Jones, A. D.; Bryant, B. A. Genetic Manipulation of Carotenoids Biosynthesis in Green Sulfur Bacterium. Chlorobium tepidum. J. Bacteriol. 2004, 186 (16), 5210−5220. (162) Krubasik, P.; Sandmann, G. Molecular Evolution of Lycopene Cyclases Involved in the Formation of Carotenoids with Ionone end Groups. Biochem. Soc. Trans. 2000, 28 (6), 806−810. (163) Estrada, A. Z.; Maier, D.; Scherzinger, D.; Avalos, A.; Al-Babili, S. Novel Apocarotenoid Intermediates in Neurospora crassa Mutants Imply a New Biosynthetic Reaction Sequence Leading to Neurosporaxanthin Formation. Fungal Genet. Biol. 2008, 45 (11), 1497− 1505. (164) Harborne, J. B. Phytochemical Methods: A Guide to Modern Techniques of Plant Analysis; Springer science & business media: New York, 1998; 288 pp. (165) Kong, K.; Khoo, H.; Prasad, K. N.; Ismail, A.; Tan, C.; Rajab, N. F. Revealing the Power of the Natural Red Pigment Lycopene. Molecules 2010, 15 (2), 959−987. (166) Harris, W. M.; Spurr, A. R. Chromoplasts of tomato fruits. II. The red tomato. Am. J. Bot. 1969, 56 (4), 380−389. (167) Delgado-Vargas, F.; Paredes-Lopez, O. Effects of enzymatic treatments on carotenoid extraction from Marigold flowers, (Tagetes erecta). Food Chem. 1997, 58 (3), 255−258. (168) Barzana, E.; Rubio, D.; Santamaria, R. I.; Garcia-Correa, O.; Garcia, F.; Ridaura Sanz, V. E.; López-Munguía, A. Enzyme-mediated solvent extraction of carotenoids from marigold flower (Tagetes erecta). J. Agric. Food Chem. 2002, 50 (16), 4491−4496. (169) Santamaria, R. I.; Reyes-Duarte, M. D.; Barzana, E.; Fernando, D.; Gama, F. M.; Mota, M.; Lopez-Munguia, A. Selective enzymemediated extraction of capsaicinoids and carotenoids from Chilli Guajillo Puya (Capsicum annum L.) using ethanol as solvent. J. Agric. Food Chem. 2000, 48 (7), 3063−3067. (170) Sampathu, S. R. D.; Naidu, M. M.; Sowbhagya, H. B.; Naik, J. P.; Krishnamurthy, N. A process for making chilli oleoresin of improved quality, US Patent 7097867. Publication date: August 29, 2006. (171) Tevini, M.; Delong, H.; Heene, E.; Schmitt, A. New type of carrot juice made from lycopene containing carrots. Flussig-Obst 2005, 72, 176−177. (172) Sharma, A. K.; Sarkar, B. C.; Sharma, H. K. Optimization of enzymatic process parameters for increased juice yield from carrot (Daucus carota L.) using response surface methodology. Eur. Food Res. Technol. 2005, 221 (1−2), 106−112. (173) Stoll, T.; Schweiggert, U.; Schieber, A.; Carle, R. Process for the recovery of a carotene rich functional food ingredient from carrot pomace by enzymatic liquification. Innovative Food Sci. Emerging Technol. 2003, 4 (4), 415−423. (174) Dubodel, N. P.; Spravink, E. V.; Sikorskaya, W. L. Isolation of food dye from tomato products. Pishch Prom St. 1995, 1, 16. (175) Ranalli, A.; Lucera, L.; Contento, S.; Simone, N.; Del Re, P. Bioactive constituents, flavours and aroma of virgin oils obtained by processing olives with a natural enzyme extract. Eur. J. Lipid Sci. Technol. 2004, 106 (3), 187−197. (176) Ranalli, A.; Malfatti, A.; Pollastri, L.; Contento, S.; Lucera, L. Analytical quality and genuiness of enzyme extracted virgin olive oil. J. Food Qual. 2003, 26 (2), 149−164. (177) Lenucci, M. S.; De Caroli, M.; Marrese, P. P.; Iurlaro, A.; Rescio, L.; Böhm, V.; Dalessandro, G.; Piro, G. Enzyme-aided extraction of lycopene from high-pigment tomato cultivars by supercritical carbon dioxide. Food Chem. 2015, 170, 193−202. (178) Andreea, B.; Augusta, L.; Adela, P.; Sanda, A.; Claudiu, B.; Constantin, B. Using Cellulases and Pectinases to Improve Better Extraction of Carotenoids from the Marigold Flowers (Tagetes erecta L.). Bulletin UASVM Animal Science and Biotechnologies 2010, 67 (1− 2), 369−373. 5943


Review


(202) McHugh, M. A.; Krukonis, V. J. Supercritical fluid extraction: Principles and practice, 2nd ed.; Brenner, H., Ed.; Elsevier: Amsterdam, 1994; 608 pp. (203) Bertucco, A.; Vetter, G.; Eds. High pressure process technology: Fundamentals and applications; Elsevier: Amsterdam, 2001; Vol. 9, 684 pp. (204) Arai, Y.; Sako, T.; Takebayashij, Y.; Eds. Supercritical fluids. Molecular interactions, physical properties, and new applications; Springer Science & Business Media: Berlin, 2002; 448 pp. (205) Baysal, T.; Ersus, S.; Starmans, D. A. J. Supercritical CO2 Extraction of β-Carotene and Lycopene from Tomato Paste Waste. J. Agric. Food Chem. 2000, 48 (11), 5507−5511. (206) Saeid, A. Effects of extraction and purification methods on degradation kinetics and stability of lycopene from watermelon under storage conditions, MSc thesis, Hajee Mohammad Danesh Science and Technology University, Dinajpur, 2005. (207) Jarén-Galán, M.; Nienaber, U.; Schwartz, S. J. Paprika (Capsicum annuum) oleoresin extraction with supercritical carbon dioxide. J. Agric. Food Chem. 1999, 47 (9), 3558−3564. (208) Vesper, H.; Nitz, S. Composition of extracts from paprika (Capsicum annuum L.) obtained by conventional and supercritical fluid extraction. Adv. Food Sci. 1997, 19 (5−6), 172−177. (209) Gómez-Prieto, M. S.; Caja, M. M.; Herraiz, M.; Santa-María, G. Supercritical Fluid Extraction of all-trans-Lycopene from Tomato. J. Agric. Food Chem. 2003, 51 (1), 3−7. (210) Durante, M.; Lenucci, M. S.; D’Amico, L.; Piro, G.; Mita, G. Effect of drying and co-matrix addition on the yield and quality of supercritical CO2 extracted pumpkin (Cucurbita moschata Duch.) oil. Food Chem. 2014, 148, 314−320. (211) Bashipour, F.; Ghoreishi, S. M. Experimental Optimization of Supercritical Extraction of β-carotene from Aloe barbadensis Miller via Genetic Algorithm. J. Supercrit. Fluids 2012, 72, 312−319. (212) Kehili, M.; Kammlott, M.; Choura, S.; Zammel, A.; Zetzl, C.; Smirnova, I.; Allouche, N.; Sayadi, S. Supercritical CO2 extraction and antioxidant activity of lycopene and β-carotene-enriched oleoresin from tomato (Lycopersicum esculentum L.) peels by-product of a Tunisian industry. Food Bioprod. Process. 2017, 102, 340−349. (213) Wang, X.; Wang, C.; Zha, X.; Mei, Y.; Xia, J.; Jiao, Z. Supercritical carbon dioxide extraction of β-carotene and α-tocopherol from pumpkin: a Box-Behnken design for extraction variables. Anal. Methods 2017, 9 (2), 294−303. (214) Zaghdoudi, K.; Framboisier, X.; Frochot, C.; Vanderesse, R.; Barth, D.; Kalthoum-Cherif, J.; Blanchard, F.; Guiavarc’h, Y. Response surface methodology applied to Supercritical Fluid Extraction (SFE) of carotenoids from Persimmon (Diospyros kaki L.). Food Chem. 2016, 208, 209−219. (215) Shi, X.; Wu, H.; Shi, J.; Xue, S. J.; Wang, D.; Wang, W.; Cheng, A.; Gong, Z.; Chen, X.; Wang, C. Effect of modifier on the composition and antioxidant activity of carotenoid extracts from pumpkin (Cucurbita maxima) by supercritical CO2. LWT - Food Sci. Technol. 2013, 51 (2), 433−440. (216) Shi, J.; Yi, C.; Ye, X.; Xue, S.; Jiang, Y.; Ma, Y.; Liu, D. Effects of supercritical CO2 fluid parameters on chemical composition and yield of carotenoids extracted from pumpkin. LWT - Food Sci. Technol. 2010, 43 (1), 39−44. (217) Xu, X.; Gao, Y.; Liu, G.; Wang, Q.; Zhao, J. Optimization of supercritical carbon dioxide extraction of sea buckthorn (Hippophae thamnoides L.) oil using response surface methodology. LWT−Food Sci. Technol. 2008, 41 (7), 1223−1231. (218) Ma, Q.; Xu, X.; Gao, Y.; Wang, Q.; Zhao, J. Optimisation of supercritical carbon dioxide extraction of lutein esters from marigold (Tagetes erect L.) with soybean oil as a co-solvent. Int. J. Food Sci. Technol. 2008, 43 (10), 1763−1769. (219) Joslin, C. G.; Gray, C. G.; Goldman, S. Solubility in supercritical fluids from the virial equation of state. Mol. Phys. 1996, 89 (2), 489−503. (220) Cygnarowicz, M. L.; Maxwell, R. J.; Seider, W. D. Equilibrium solubilities of β-carotene in supercritical carbon dioxide. Fluid Phase Equilib. 1990, 59 (1), 57−71.

(179) Zuorro, A.; Lavecchia, R. Mild enzymatic method for the extraction of lycopene from tomato paste. Biotechnol. Biotechnol. Equip. 2010, 24 (2), 1854−1857. (180) Roberts, K., Ed. Handbook of Plant Science; John Wiley & Sons: Chichester, U.K., 2007; Vol. 2, 1645 pp. (181) Sowbhagya, H. B.; Chitra, V. N. Enzyme-Assisted Extraction of Flavorings and Colorants from Plant Materials. Crit. Rev. Food Sci. Nutr. 2010, 50 (2), 146−161. (182) Dominguez, H.; Nunez, M. J.; Loma, Y. M. Oil extractability from enzymatically treated soybean and sunflower, range of operational variables. Food Chem. 1993, 46 (3), 277−284. (183) Mcglone, O. C.; Canales, A. L. M.; Carter, J. V. Coconut oil extraction by a new enzymatic process. J. Food Sci. 1986, 51 (3), 695− 697. (184) Buenrostro, M.; Lopez-Munguia, A. Enzymatic extraction of avocado oil. Biotechnol. Lett. 1986, 8 (7), 505−506. (185) Hernandez, N.; Rodriguez-Alegría, M. E.; Gonzalez, F.; LopezMunguia, A. Enzymatic treatment of rice bran to improve processing. J. Am. Oil Chem. Soc. 2000, 77 (2), 177−180. (186) Micard, V.; Renard, C. M. G. C.; Thibault, J. F. Studies on enzymic release of ferulic acid from sugar beet pulp. Lebensm. Wiss. Technol. 1994, 27 (1), 59−66. (187) Ç inar, I. Effects of cellulase and pectinase concentrations on the colour yield of enzyme extracted plant carotenoids. Process Biochem. 2005, 40 (2), 945−949. (188) Sihvonen, M.; Jarvenpaa, E.; Hietaniemi, V.; Huopalahti, R. Advances in supercritical carbon dioxide technologies. Trends Food Sci. Technol. 1999, 10 (6−7), 217−222. (189) Shi, J.; Kassama, L. S.; Kakuda, Y. Supercritical Fluid Technology for Extraction of Bioactive Components. In Functional Food Ingredients and Nutraceuticals Processing Technologies, 2nd ed.; Shi, J., Ed.; CRC press: New York, 2007; 659 pp. (190) Kikic, I.; Eva, F. Application of Supercritical Fluids in Pharmaceutical Industry. Olaj. Szappan. Kozmetika 2002, 51, 10−17. (191) Uquiche, E.; del Valle, J. M.; Ortiz, J. Supercritical carbon dioxide extraction of red pepper (Capsicum annuum L.) oleoresin. J. Food Eng. 2004, 65 (1), 55−66. (192) Mukhopadhyay, M. Natural Extracts Using Supercritical Carbon Dioxide. CRC Press: Boca Raton, FL, 2000; 360 pp. (193) Macias-Sanchez, M. D.; Mantell, C.; Rodriguez, M.; Martinez de la Ossa, E.; Lubian, L. M.; Montero, O. Supercritical fluid extraction of carotenoids and chlorophyll from Nannochloropsis gaditana. J. Food Eng. 2005, 66 (2), 245−251. (194) Rizvi, S. S. H.; Yu, Z. R.; Bhaskar, A. R.; Chidambara, R. C. B. Fundamentals of processing with supercritical fluids. In Supercritical Fluids Processing of Food and Biomaterials; Rizvi, S. S. H., Ed.; Chapman and Hall: Glasgow, 1994. (195) Del Valle, J. M.; Napolitano, P.; Fuentes, N. Estimation of Relevant Mass Transfer Parameters for the Extraction of Packed Substrate Beds Using Supercritical Fluids. Ind. Eng. Chem. Res. 2000, 39 (12), 4720−4728. (196) Shi, J.; Xue, S. J.; Kassama, L.; Ye, X.. Extracting of healthpromoting components by supercritical-C02 fluid process. In Functional Food Ingredients and Nutraceuticals: Processing Technologies, 2nd ed.; Shi, J., Ed.; CRC Press: New York, 2005; 659 pp. (197) King, J. W.; Hill, H. H., Jr.; Lee, M. L. Analytical supercritical fluid chromatography and extraction. In: Supplement and Cumulative Index, anonymous, 2nd ed.; Baetzold, R. C.; Rossiter, B. W.; Eds.; John Wiley & Sons: New York, 1993; pp 1−83. (198) Brunner, G. Supercritical fluids: technology and application to food processing. J. Food Eng. 2005, 67 (1−2), 21−33. (199) King, M. B.; Bott, T. R., Eds. Extraction of natural products using near-critical solvents; Champman & Hall: London, 1993; 325 pp. (200) Brunner, G. Gas extraction. An introduction to fundamentals of supercritical fluids and the application to separation processes. Springer Science & Business Media: New York, 2013; Vol. 4, 387 pp. (201) Brunner, G. Fractionation of fats with supercritical carbon dioxide. Eur. J. Lipid Sci. Technol. 2000, 102 (3), 240−244. 5944


Review


compounds from Adathoda vasica and. Alexandria Eng. J. 2016, 55 (1), 141−150. (241) Harwood, L. M.; Moody, C. J. Experimental organic chemistry: Principles and Practice; Blackwell Scientific Publications: Oxford, 1989; 778 pp. (242) Bonnie, T. P.; Choo, Y. M. Oxidation and thermal degradation of carotenoids. J. Oil Palm. Res. 1990, 11 (1), 62−78. (243) Kanasawud, P. J.; Crouzet, J. C. Mechanism of formation of volatile compounds by thermal degradation of carotenoids in aqueous medium. 1..beta.-Carotene degradation. J. Agric. Food Chem. 1990, 38 (1), 237−243. (244) Luque-De-Castro, M. D.; Garcia-Ayuso, L. E. Soxhlet extraction of solid material: An outdated technique with a promising innovative future. Anal. Chim. Acta 1998, 369 (1−2), 1−10. (245) Luque-García, J. L.; Luque de Castro, M. D. Ultrasoundassisted Soxhlet extraction: an expeditive approach for solid sample treatment. Application to the extraction of total fat from oleaginous seeds. J. Chromatogr. A 2004, 1034 (1−2), 237−242. (246) Fakirov, S. Modified Soxhlet apparatus for high-temperature extraction. J. Appl. Polym. Sci. 2006, 102, 2013−2014. (247) Bangun, N.; Sembiring, S. B.; Putri, N. K.; Karo, J. A. K. Extraction of carotenoids from crude palm oil using M-silicate, Mpolystyrene sulfonate (M = Mg, Ca) and a collector. International Conference on Chemical Engineering, Yogyakarta, 2015. (248) Yahaya, M. Z. B. Study on factors affecting extraction of carotene from carrot by using Soxhlet extraction method. BSc thesis, University of Malaysia Pahang, Pekan, 2013. (249) Mezzomo, N.; Maestri, B.; Dos Santos, R. L.; Maraschin, M.; Ferreira, S. R. S. Pink Shrimp (P. brasiliensis and P. paulensis) Processing Residue: Influence of Extraction Method on Carotenoid Concentration. Talanta 2011, 85 (3), 1383−1391. (250) Kaderides, K.; Goula, A. M.; Adamopoulos, K. G. A process for turning pomegranate peels into a valuable food ingredient using ultrasound-assisted extraction and encapsulation. Innovative Food Sci. Emerging Technol. 2015, 31, 204−215. (251) Pingret, D.; Fabiano-Tixier, A. S.; Le Bourvellec, C.; Renard, C. M.; Chemat, F. Lab and pilot-scale ultrasound-assisted water extraction of polyphenols from apple pomace. J. Food Eng. 2012, 111 (1), 73−81. (252) Shirsath, S. R.; Sonawane, S. H.; Gogate, P. R. Intensification of extraction of natural products using ultrasonic irradiations - A review of current status. Chem. Eng. Process. 2012, 53, 10−23. (253) Purohit, A. J.; Gogate, P. R. Ultrasound-assisted extraction of β-carotene from waste carrot residue: effect of operating parameters and type of ultrasonic irradiation. Sep. Sci. Technol. 2015, 50 (10), 1507−1517. (254) Maran, J. P.; Priya, B. Natural pigments extraction from Basella Rubra L fruits by ultrasound-assisted extraction combined with boxBehnken response surface design. Sep. Sci. Technol. 2015, 50 (10), 1532−1540. (255) Li, Y.; Fabiano-Tixier, A. S.; Tomao, V.; Cravotto, G.; Chemat, F. Green ultrasound-assisted extraction of carotenoids based on the bio-refinery concept using sunflower oil as an alternative solvent. Ultrason. Sonochem. 2013, 20 (1), 12−18. (256) Goula, A. M.; Ververi, M.; Adamopoulou, A.; Kaderides, K. Green ultrasound-assisted extraction of carotenoids from pomegranate wastes using vegetable oils. Ultrason. Sonochem. 2017, 34, 821−830. (257) Almahy, H. A.; Ali, M. A.; Ali, A. A. Extraction of Carotenoids as Natural dyes from the Daucus carota Linn (carrot) using Ultrasound in Kingdom of Saudi Arabia. Res. J. Chem. Sci. 2013, 3 (1), 63−66. (258) Luo, D.; Qiu, T.; Lu, Q. Ultrasound-assisted extraction of ginsenosides in supercritical CO2 reverse microemulsions. J. Sci. Food Agric. 2007, 87 (3), 431−436. (259) Kumcuoglu, S.; Yilmaz, T.; Tavman, S. Ultrasound assisted extraction of lycopene from tomato processing wastes. J. Food Sci. Technol. 2014, 51 (12), 4102−4107. (260) Britton, G. General Carotenoid Methods. Methods Enzymol. 1985, 111, 113−149.

(221) Tamelli, F.; Guclu-Ustundag, O. Solubility behaviour of ternary systems of lipids, cosolvents and supercritical carbon dioxide, 1−6 (Available at http://www.isasf.net/fileadmin/files/Docs/Versailles/ Papers/PTs27.pdf.) (Accessed November 5, 2017). (222) Wong, J. M.; Johnston, K. P. Solubilization of biomolecules in carbon dioxide based supercritical fluids. Biotechnol. Prog. 1986, 2 (1), 29−39. (223) Vincent, M. F.; Kazarian, S. G.; West, B. L.; Berkner, J. A.; Bright, F. V.; Liotta, C. L.; Eckert, C. A. Cosolvent Effects of Modified Supercritical Carbon Dioxide on Cross-Linked Poly (dimethylsiloxane). J. Phys. Chem. B 1998, 102 (12), 2176−2186. (224) Quancheng, Z.; Guihua, S.; Hong, J.; Moucheng, W. Concentration of tocopherols by supercritical carbon dioxide with cosolvents. Eur. Food Res. Technol. 2004, 219 (4), 398−402. (225) Mongkholkhajornsilp, D.; Doulas, S.; Douglas, P. L.; Elkamel, A.; Teppaitoon, W.; Pongamphai, S. Supercritical CO2 extraction of nimbin from neem seeds − a modeling study. J. Food Eng. 2005, 71 (4), 331−340. (226) Zahedi, G.; Azizi, S.; Hatami, T.; Sheikhattar, L. Gray Box Modeling of Supercritical Nimbin Extraction from Neem Seeds Using Methanol as Co-Solvent. Open Chem. Eng. J. 2010, 4, 21−30. (227) Veggi, P. C.; Martinez, J.; Meireles, M. A. A. Fundamentals of Microwave Extraction.. Microwave-assisted Extraction for Bioactive Compounds: Theory and Practice; Chemat, F.; Cravotto, G., Eds.; Springer science: New York, 2013; 240 pp. (228) Hiranvarachat, B.; Devahastin, S. Enhancement of microwaveassisted extraction via intermittent radiation: Extraction of carotenoids from carrot peels. J. Food Eng. 2014, 126, 17−26. (229) Saini, R. K.; Keum, Y. S. Carotenoid extraction methods: A review of recent developments. Food Chem. 2018, 240, 90−103. (230) Li, Y.; Fabiano-Tixier, A. S.; Abert-Vian, M.; Chemat, F. Microwave-Assisted Extraction of Antioxidants and Food Colors. In Microwave-assisted Extraction for Bioactive Compounds: Theory and Practice; Chemat, F.; Cravotto, G., Eds.; Springer science: New York, 2013; 240 pp. (231) Paré, J. R. J. Microwave assisted process for extraction and apparatus therefore. CA patent no. 2055390. Publication date: December 06, 2006. (232) Paré, J. R. J.; Sigouin, M.; Lapointe, J. Extraction of natural products assisted by microwaves. EP patent no. 0398798. Publication date: November 22, 1990. (233) Paré, J. R. J.; Sigouin, M.; Lapointe, J. Microwave-assisted natural product extraction. US patent no. 5002784. Publication date: March 26, 1991. (234) Paré, J. R. J. Microwave extraction of volatile oils. US patent no. US 5338557. Publication date: August 16, 1994. (235) Vian, M. A.; Fernandez, X.; Visinoni, F.; Chemat, F. Microwave hydrodiffusion and gravity, a new technique for extraction of essential oils. J. Chromatogr. A 2008, 1190 (1−2), 14−17. (236) Ho, K. K. H. Y.; Ferruzzi, M. G.; Liceaga, A. M.; San MartínGonzález, M. F. Microwave-assisted extraction of lycopene in tomato peels: Effect of extraction conditions on all-trans and cis-isomer yields. LWT - Food Sci. Technol. 2015, 62 (1), 160−168. (237) Kiss, G. A. C.; Forgacs, E.; Cserhati, T.; Mota, T.; Morais, H.; Ramos, A. Optimization of the microwave-assisted extraction of pigments from paprika (Capsicum annuum L.) powders. J. Chromatogr. A 2000, 889 (1−2), 41−49. (238) Hiranvarachat, B.; Devahastin, S.; Chiewchan, N.; Raghavan, G. S. V. Structural modification by different pretreatment methods to enhance microwaveassisted extraction of β-carotene from carrots. J. Food Eng. 2013, 115 (2), 190−197. (239) Pasquet, V.; Chérouvrier, J. R.; Farhat, F.; Thiéry, V.; Piot, J. M.; Bérard, J. B.; Kaas, R.; Serive, B.; Patrice, T.; Cadoret, J. P.; Picot, P. Study on the microalgal pigments extraction process: Performance of microwave assisted extraction. Process Biochem. 2011, 46 (1), 59− 67. (240) Simha, P.; Mathew, M.; Ganesapillai, M. Empirical modeling of drying kinetics and microwave assisted extraction of bioactive 5945


Review

Journal of Agricultural and Food Chemistry (261) Mercadante, A. Z.; Rodrigues, D. B.; Petry, F. C.; Mariutti, L. R. B. Carotenoid esters in foods - A review and practical directions on analysis and occurrence. Food Res. Int. 2017, 99 (2), 830−850. (262) Inbaraj, B. S.; Lu, H.; Hung, C. F.; Wu, W. B.; Lin, C. L.; Chen, B. H. Determination of carotenoids and their esters in fruits of Lycium barbarum Linnaeus by HPLC-DAD-APCI-MS. J. Pharm. Biomed. Anal. 2008, 47 (4−5), 812−818. (263) Irakli, M. N.; Samanidou, V. F.; Papadoyannis, I. N. Development and validation of an HPLC method for the simultaneous determination of tocopherols, tocotrienols and carotenoids in cereals after solid-phase extraction. J. Sep. Sci. 2011, 34 (12), 1375−1382. (264) Divya, P.; Puthusseri, B.; Neelwarne, B. Carotenoid content, its stability during drying and the antioxidant activity of commercial coriander (Coriandrum sativum L.) varieties. Food Res. Int. 2012, 45 (1), 342−350. (265) Sagratini, G.; Allegrini, M.; Caprioli, C. G.; Giardina, D.; Maggi, F.; Ricciutelli, M.; Sirocchi, V.; Vittori, S. Simultaneous determination of squalene, α-tocopherol and β-carotene in table olives by solid phase extraction and high-performance liquid chromatography with diode array detection. Food. Anal Methods. 2013, 6 (1), 54−60. (266) Granado, F.; Olmedilla, B.; Gil-Martinez, E.; Blanco, I. A fast, reliable and low-cost saponification protocol for analysis of carotenoids in vegetables. J. Food Compos. Anal. 2001, 14 (5), 479−489. (267) Niizu, P. Y.; Rodriguez-Amaya, D. B. New data on the carotenoid composition of raw material salad vegetables. J. Food Compos. Anal. 2005, 18 (8), 739−749. (268) de Munter, L.; Maasland, D. H.; van den Brandt, P. A.; Kremer, B.; Schouten, L. J. Vitamin and carotenoid intake and risk of head-neck cancer subtypes in the Netherlands. Am. J. Clin. Nutr. 2015, 102 (2), 420−432. (269) Lu, M. S.; Fang, Y. J.; Chen, Y. M.; Luo, W. P.; Pan, Z. Z.; Zhong, X.; Zhang, C. X. Higher intake of carotenoid is associated with a lower risk of colorectal cancer in Chinese adults: a case-control study. Eur. J. Nutr. 2015, 54 (4), 619−628. (270) Polesel, J.; Negri, E.; Serraino, D.; Parpinel, M.; Barzan, L.; Libra, M.; Bosetti, C.; Garavello, W.; Montella, M.; La Vecchia, C.; Franceschi, S.; Talamini, R. Dietary intakes of carotenoids and other nutrients in the risk of nasopharyngeal carcinoma: a case−control study in Italy. Br. J. Cancer 2012, 107 (9), 1580−1583. (271) Sluijs, I.; Cadier, E.; Beulens, J. W. W.; van der A, D. L.; Spijkerman, A. M. W.; van der Schouw, Y. T. Dietary intake of carotenoids and risk of type 2 diabetes. Nutr., Metab. Cardiovasc. Dis. 2015, 25 (4), 376−381. (272) Cocate, P. G.; Natali, A. J.; Alfenas, R. C.; de Oliveira, A.; dos Santos, E. C.; Hermsdorff, H. H. Carotenoid consumption is related to lower lipid oxidation and DNA damage in middle-aged men. Br. J. Nutr. 2015, 114 (2), 257−264. (273) Lan, Q. Y.; Zhang, Y. J.; Liao, G. C.; Zhou, R. F.; Zhou, Z. G.; Chen, Y. M.; Zhu, H. L. The Association between Dietary Vitamin A and Carotenes and the Risk of Primary Liver Cancer: A Case−Control Study. Nutrients 2016, 8 (10), 624. (274) Van Hoang, D.; Pham, N. M.; Lee, A. H.; Tran, D. N.; Binns, C. W. Dietary Carotenoid Intakes and Prostate Cancer Risk: A CaseControl Study from Vietnam. Nutrients 2018, 10 (1), 70. (275) Pezdirc, K.; Hutchesson, M. J.; Williams, R. L.; Rollo, M. E.; Burrows, T. L.; Wood, L. G.; Oldmeadow, C.; Collins, C. E. Consuming High-Carotenoid Fruit and Vegetables Influences Skin Yellowness and Plasma Carotenoids in Young Women: A Single-Blind Randomized Crossover Trial. J. Acad. Nutr. Diet. 2016, 116 (8), 1257− 1265. (276) Umesawa, M.; Iso, H.; Mikami, K.; Kubo, T.; Suzuki, K.; Watanabe, Y.; Mori, M.; Miki, T.; Tamakoshi, A. Relationship between vegetable and carotene intake and risk of prostate cancer: the JACC study. Br. J. Cancer 2014, 110 (3), 792−796. (277) McDonald, A. C.; Bunker, C. H.; Raman, J.; Richie, J.; Patrick, A. L. Serum carotenoid and retinol levels in African-Caribbean Tobagonian men with high prostate cancer risk in comparison with African-American men. Br. J. Nutr. 2017, 117 (8), 1128−1136.

(278) Wright, M. E.; Virtamo, J.; Hartman, A. M.; Pietinen, P.; Edwards, B. K.; Taylor, P. R.; Huttunen, J. K.; Albanes, D. Effects of alpha-tocopherol and beta-carotene supplementation on upper aerodigestive tract cancers in a large, randomized controlled trial. Cancer 2007, 109 (5), 891−898. (279) Giovannucci, E.; Ascherio, A.; Rimm, E. B.; Stampfer, M. J.; Colditz, G. A.; Willett, W. C. Intake of carotenoids and retinol in relation to risk of prostate cancer. J. Natl. Cancer. Inst 1995, 87 (23), 1767−1776. (280) Schuurman, A. G.; Goldbohm, R. A.; Brants, H. A. M.; van den Brandt, P. A. A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands). Cancer Causes Control 2002, 13 (6), 573−582. (281) Leo, M. A.; Lieber, C. S. Alcohol, vitamin A, and β-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am. J. Clin. Nutr. 1999, 69 (6), 1071−85. (282) Omenn, G. S.; Goodman, G. E.; Thornquist, M. D.; Balmes, J.; Cullen, M. R.; Glass, A.; Keogh, J. P.; Meyskens, F. L.; Valanis, B.; Barnhart, S.; Cherniack, M. G.; Brodkin, C. A.; Hammar, S. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J. Natl. Cancer Inst. 1996, 88 (21), 1550−59. (283) Albanes, D.; Heinonen, O. P.; Taylor, P. R.; Virtamo, J.; Edwards, B. K.; Rautalahti, M.; Hartman, A. M.; Palmgren, J.; Freedman, L. S.; Haapakoski, J.; Barrett, M. J.; Pietinen, P.; Malila, N.; Tala, E.; Liippo, K.; Salomaa, E. R.; Tangrea, J. A.; Teppo, L.; Askin, F. B.; Taskinen, E.; Erozan, Y.; Greenwald, P.; Huttunen, J. K. AlphaTocopherol and β-carotene supplements and lung cancer incidence in the alpha-tocopherol, β-carotene cancer prevention study: effects of base-line characteristics and study compliance. J. Natl. Cancer Inst. 1996, 88 (21), 1560−70. (284) Goodman, G. E.; Thornquist, M. D.; Balmes, J.; Cullen, M. R.; Meyskens, F. L., Jr; Omenn, G. S.; Valanis, B.; Williams, J. H., Jr The beta-carotene and retinol efficacy trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping β-carotene and retinol supplements. J. Natl. Cancer Inst. 2004, 96 (23), 1743−50. (285) Hendler, S. S. PDR for Nutritional Supplements. 2nd ed. Thomson Reuters: NJ, 2008; 788 pp. (286) Higdon, J. α-Carotene, β-Carotene, β-Cryptoxanthin, Lycopene, Lutein, and Zeaxanthin. Available at (http://lpi. oregonstate.edu/mic/dietaryfactors/phytochemicals/ carotenoids#reference157.) (Accessed November 13, 2017). (287) Van den Berg, H. Effect of lutein on β-carotene absorption and cleavage. Int. J. Vitam. Nutr Res. 1998, 68 (6), 360−65. (288) High, E. G.; Day, H. G. Effects of different amounts of lutein, squalene, phytol and related substances on the utilization of carotene and vitamin A for storage and growth in the rat. J. Nutr. 1951, 43 (2), 245−60. (289) Tang, G.; Dolnikowski, G. G.; Blanco, M. C.; Fox, J. G.; Russell, R. M. Serum carotenoids and retinoids in ferrets fed canthaxanthin. J. Nutr. Biochem. 1993, 4 (1), 58−63. (290) Chen, J.; Jiang, W.; Shao, L.; Zhong, D.; Wu, Y.; Cai, J. Association between intake of antioxidants and pancreatic cancer risk: a meta-analysis. Int. J. Food Sci. Nutr. 2016, 67 (7), 744−753. (291) Ge, X. X.; Xing, M. Y.; Lan-Fang Yu, L. F.; Shen, P. Carotenoid Intake and Esophageal Cancer Risk: a Meta-analysis. Asian Pacific J. Cancer Prev 2013, 14 (3), 1911−1918. (292) Graff, R. E.; Pettersson, A.; Lis, R. T.; Ahearn, T. U.; Markt, S. C.; Wilson, K. M.; Rider, J. R.; Fiorentino, M.; Finn, S.; Kenfield, S. A.; Loda, M.; Giovannucci, E. L.; Rosner, B.; Mucci, L. A. Dietary lycopene intake and risk of prostate cancer defined by ERG protein expression1. Am. J. Clin. Nutr. 2016, 103 (3), 851−860. (293) Iskandar, A. R.; Miao, B.; Li, X.; Hu, K. Q.; Liu, C.; Wang, X. D. β-Cryptoxanthin reduced lung tumor multiplicity and inhibited lung cancer cell motility by down-regulating nicotinic acetylcholine receptor α7 signaling. Cancer Prev. Res. 2016, 9 (11), 875−886. (294) Hayhoe, R. P. G.; Lentjes, M. A. H.; Mulligan, A. A.; Luben, R. N.; Khaw, K.-T.; Welch, A. A. Carotenoid dietary intakes and plasma 5946


Review

Journal of Agricultural and Food Chemistry concentrations are associated with heel bone ultrasound attenuation and osteoporotic fracture risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. Br. J. Nutr. 2017, 117 (10), 1439−1453. (295) Dai, Z.; Wang, R.; Ang, L. W.; Low, Y. L.; Yuan, J. M.; Koh, W. P. Protective effects of dietary carotenoids on risk of hip fracture in men: the Singapore Chinese Health Study. J. Bone Miner. Res. 2014, 29 (2), 408−417. (296) Shareck, M.; Rousseau, M. C.; Koushik, A.; Siemiatycki, J.; Parent, M. E. Inverse Association between Dietary Intake of Selected Carotenoids and Vitamin C and Risk of Lung Cancer. Front. Oncol. 2017, 7, 23. (297) Yu, N.; Su, X.; Wang, Z.; Dai, B.; Kang, J. Association of Dietary Vitamin A and β-Carotene Intake with the Risk of Lung Cancer: A Meta-Analysis of 19 Publications. Nutrients 2015, 7 (11), 9309−9324. (298) De Stefani, E.; Boffetta, P.; Deneo-Pellegrini, H.; Mendilaharsu, M.; Carzoglio, J. C.; Ronco, A.; Olivera, L. Dietary antioxidants and lung cancer risk: a case-control study in Uruguay. Nutr. Cancer 1999, 34 (1), 100−110. (299) Knekt, P.; Jarvinen, R.; Teppo, L.; Aromaa, A.; Seppanen, R. Role of various carotenoids in lung cancer prevention. J. Natl. Cancer Inst 1999, 91 (2), 182−184. (300) Marchand, J. L.; Luce, D.; Goldberg, P.; Bugel, I.; Salomon, C.; Goldberg, M. Dietary factors and the risk of lung cancer in New Caledonia (South Pacific). Nutr. Cancer 2002, 42 (1), 18−24. (301) Michaud, D. S.; Feskanich, D.; Rimm, E. B.; Colditz, G. A.; Speizer, F. E.; Willett, W. C.; Giovannucci, E. Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts. Am. J. Clin. Nutr. 2000, 72 (4), 990−997. (302) Voorrips, L. E.; Goldbohm, R. A.; Brants, H. A.; van Poppel, G. A.; Sturmans, F.; Hermus, R. J.; van den Brandt, P. A. A prospective cohort study on antioxidant and folate intake and male lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2000, 9 (4), 357−365. (303) American Cancer Society. Cancer Facts & Figures 2016; American Cancer Society: Atlanta, 2016.

5947


Selected Methods of Extracting Carotenoids, Characterization, and

Recommend Documents