Genus Hylocereus: Beneficial Phytochemicals, Nutritional Importance, and Biological Relevance—Areview

Received: 13 November 2017 | Revised: 29 November 2017 | Accepted: 6 December 2017 DOI: 10.1111/jfbc.12491

REVIEW

Genus Hylocereus: Beneficial phytochemicals, nutritional importance, and biological relevance—Areview

Sabrin Ragab Mohamed Ibrahim1,2 | Gamal Abdallah Mohamed3,4 | Amgad Ibrahim Mansour Khedr5 | Mohamed Fathalla Zayed1,6 | Amal Abd-Elmoneim Soliman El-Kholy7,8

1Department of Pharmacognosy and Pharmaceutical Chemistry, College of Abstract Pharmacy, Taibah University, Al Madinah Al The genus Hylocereus (family Cactaceae) includes about 16 species. Now its reputation is spreading Munawarah 30078, Saudi Arabia everywhere in the world due to its fruit (pitaya or pitahaya or dragon fruit), which is one of the most 2Department of Pharmacognosy, Faculty of popular and widely used functional foods in the world. The fruit is a wealthy provenance of vitamins, Pharmacy, Assiut University, Assiut 71526, Egypt minerals, antioxidants, and fiber. The ethno-pharmacological history of this genus indicated that it 3Department of Natural Products and possesses antioxidant, anticancer, antimicrobial, hepato-protective, antihyperlipidemic, antidiabetic, Alternative Medicine, Faculty of Pharmacy, and wound healing activities. Furthermore, it has been used for the treatment of cough, asthma, King Abdulaziz University, Jeddah, 21589, hyperactivity, tuberculosis, bronchitis, mumps, diabetes, and cervical lymph node tuberculosis. Differ- Saudi Arabia ent chemical constituents have been reported from this genus as betalains, flavonoids, phenolic 4Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut acids, phenylpropanoids, triterpenes, sterols, fatty acids, etc. The current review focuses on the uses, Branch, Assiut 71524, Egypt botanical characterization, chemical constituents, nutritional importance, biological activities, and 5 Department of Pharmacognosy, Faculty of safety of Hylocereus species. Also, biosynthetic pathways of betalains have been discussed. Pharmacy, Port Said University, Port Said 42526, Egypt Practical applications 6 Department of Pharmaceutical Chemistry, Pitaya fruit is one of the most known fruit that is commercially grown in different countries of the Faculty of Pharmacy, Al-Azhar University, world for its nutritional advantages. It has acquired a wide acceptance for its pharmacological actions Cairo, Egypt 7Department of Clinical and Hospital against a variety of ailments. The present review revealed that pitaya contains various bioactive phyto- Pharmacy, College of Pharmacy, Taibah constituents which might participate directly or indirectly in their highlighted biological effects. University, Al Madinah Al Munawwarah Therefore, these compounds can be taken into account as favorable candidates for the development 30078, Saudi Arabia of effective and novel pharmaceutical leads. Deep phytochemical studies of pitaya fruit and its phar- 8Department of Clinical Pharmacy, Faculty of Pharmacy, Ain-Shams University, Cairo macological effects, especially the mechanism of action of its constituents to clarify the relation 11566, Egypt between traditional uses and pharmacological activities will obviously be the focus of further research.

Correspondence Sabrin Ragab Mohamed Ibrahim, KEYWORDS Department of Pharmacognosy and Betalains, biological activities, Cactaceae, chemical constituents, Hylocereus, uses Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al Madinah Al Munawarah 30078, Saudi Arabia. Emails: [email protected]; [email protected]

Abbreviations: AA, ascorbic acid; ABTS, 2,20-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid; ADM, adriamycin; AEDA, aroma extract dilution analysis; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; B16F10, mus musculus skin melanoma; Bcap-37, human breast cancer cell line; CCl4, carbon tetrachloride; CO2, carbon dioxide; Cyt P 450, cytochrome P450; DAA, dehydroascorbic acid; DNA, deoxyribonucleic acid; DOPA, dopamine; DPPH, 2,2-diphenyl-1- picrylhydrazyl; ESR, electron spin resonance spectroscopy; FACS, fluorescence activated cell sorting; FRAP, ferric reducing antioxidant power; FTC, ferric thiocyanate;

GSH, glutathione; H2O2, hydrogen peroxide; HDL-C, high density lipoprotein cholesterol; HepG2, liver cancer cells; HFD, high fructose diet; HO-1, heme oxygenase 1;

HT-29, human colonic adenocarcinoma; Huh7, human liver hepatoma; IC50, half maximal inhibitory concentration; IL-1b, interleukin-1b; LDL-C, low density lipoprotein; MAS, marker-assisted selection; MGC-803, human gastric cancer cell line; MIC, minimum inhibitory concentration; mol-TEA/mol-compound, mol-trolox equivalent activity/mol compound; NCI, National Cancer Institute; NF-jB, nuclear factor-jappa beta; NOAEL, no-observed-adverse-effect level; Nrf2, nuclear factor-erythroid- derived 2-like 2; PC3, human prostate; PON1, paraoxonase 1; QTL, quantitative trait loci; SPME, solid phase micro-extraction; SRB, sulphorhodamine-B; TAC, total antioxidant capacity; TBA, thiobarbituric acid; TEAC, trolox equivalent antioxidant capacity; TG, triglycerides; UDP-G, uridine diphosphate glucose; VEGF, vascular endothelial growth factor; WRL68, embryonic normal liver cells.

JFoodBiochem. 2018;e12491. wileyonlinelibrary.com/journal/jfbc VC 2018 Wiley Periodicals, Inc. | 1of29 https://doi.org/10.1111/jfbc.12491 2of29 | IBRAHIM ET AL.

1 | INTRODUCTION special names have been allocated to Hylocereus genotypes based on scales number, morphology, and shape. The most popular Hylocereus The genus Hylocereus (A. Berger) Britton & Rose belongs to family Cac- genotypes are Rosa, San Ignacio, and Orejona in Nicaragua. Cisneros taceae. The species of this genus are vine cacti (climbing with aerial and Tel-Zur (2012) stated that the molecular techniques used to iden- roots) with three angled stems and glabrous large-scaled berry tify the different genotypes of Hylocereus sp. are the molecular (Montoya-Arroyo et al., 2014). It is grown ornamentally in gardens and markers, fluorescence activated cell sorting (FACS), marker-assisted indoors for its big, fragrant, and night-blooming flowers. Now, its repu- selection (MAS), and quantitative trait loci (QTL) (Cisneros & Tel-Zur, tation is spreading everywhere in the world due to its fruit. The plant is 2012). Currently, pitaya is a quite economical product for the conven- grown in the tropical region but it must be conserved from subfreezing tional producer because its cultivation requires little or no investment. temperatures and intensive solar radiation when planted under sub- Subsequently, it can be considered as an alternative crop with high tropical states (Siddiq & Nasir, 2012). The members of family Cactaceae commercial potential (Gutierrez, Solís, Baez, & Flores, 2007). The fruits became popular in Europe after American’s discovery. H. megalanthus have played a remarkable role as medicine, food, and ornamentally. The is native of Venezuela, Colombia, Bolivia, Peru, and Ecuador. H. undatus fruit is a rich source of vitamins (B1, B2, B3, C, niacin, pyridoxine, and is native of South America, Mexico, Martinica, and Colombia (Siddiq & cobalamin), minerals (calcium, potassium, phosphorus, sodium, iron, and Nasir, 2012). However, H. trigonus is considered to be native of Brazil, zinc), protein, fat, carbohydrate, and fiber (Halimoon & Abdul Hasan, Uruguay, and Colombia. Hylocereus is cultivated in Nicaragua, Guate- 2010; Jaafar, Abdul Rahman, Mahmod, & Vasudevan, 2009). It is also mala, Mexico, Costa Rica, Colombia, Peru, and Venezuela. Also, it is rich in phytoalbumins, flavonoids, phenolics, and betacyanins, which are come into China, Bahamas, Bermuda, Australia, United States (Florida extremely valued for their antioxidant potential (Elfi Susanti, Utomo, and California), India, Thailand, Taiwan, Malaysia, Philippines, Vietnam, Syukri, & Redjeki, 2012; Jaafar et al., 2009). The flowers of H. undatus Cambodia, Indonesia, and Israel (Choo & Yong, 2011; Lim, Tan, Karim, have been utilized for treating cough, hyperactivity, tuberculosis, bron- Ariffin, & Bakar, 2010). The common name of these fruits is pitaya or chitis, mumps, diabetes, and cervical lymph node tuberculosis for a long pitahaya. Pitaya is often called “dragon fruit” in Asia. It is a medium- time in the southern China folk medicine (Gutierrez et al., 2007; Wu large berry-bearing scales or bracts on the fruit skin, which resembles a et al., 2011). Dragon fruit improves the digestion process due to its dragon (Wybraniec et al., 2001). The pulp is juicy and delicate with fiber, which prevents cancer of the colon and diabetes, neutralizes toxic abundant soft small seeds (Nerd & Mizrahi, 1998). Hylocereus genus materials as heavy metals, and reduces high blood pressure and levels includes about 16 species (Choo & Yong, 2011; Royal Botanic Garden of cholesterol (Jaafar et al., 2009). The regular consumption of dragon Kew, 2016). They may be distinguished from each other by either the fruit can help against cough and asthma. H. undatus flowers and leaves color of soft fleshy center (mesocarp or endocarp) which has the seeds were traditionally utilized by the Mayas as cicatrizing agent, diuretic, and/or the pulpy skin’s color (exocarp). Morphologically, the observed and hypoglycemic (Wybraniec et al., 2001). H. polyrhizus pulp has been amount of seeds to fruit is low. The most vastly commercially grown utilized for the manufacturing of red-violet colored ice cream, juices, species are H. megalanthus (yellow Pitaya, white pulp with yellow skin), and lipstick (Choo & Yong, 2011). In Taiwan, the fruit has been used as H. polyrhizus (Red Pitaya, red pulp with pink skin), and H. undatus a food substitute for rice and as a dietary fiber source for diabetic per- (White Pitaya, white pulp with pink skin) as well as their varieties and sons (Elfi Susanti et al., 2012). Pharmacological study displayed that hybrids (Choo & Yong, 2011) (Figure 1; Table 1). In Central America, Hylocereus had various bioactivities as antioxidant, anticancer,

FIGURE 1 Photos of the most common Hylocereus species fruits IBRAHIM ET AL. | 3of29

TABLE 1 Botanical characteristics of the common Hylocereus species

Species name Botanical characteristics Reference

H. polyrhizus (F.A.C. Web.) Britton & Flowers are 25–30 cm long. Perianth is red, especially at the tips. Stigma is Ariffin et al. (2009); Le Bellec Rose (syn. H. monacanthus) (red short, lobed, and yellow in color. Fruit is 10–12 cm long and 130–350 g et al. (2006); Lim (2012); pitaya or red pitaya with red flesh) in weight. It is oblong and covered with scales with different size. It has Siddiq and Nasir (2012); a red flesh with many small black seeds, pleasant flesh texture and Wybraniec et al. (2001) sweeter taste. H. polyrhizus has two varieties; pink- and yellow-skinned.

H. venezuelensis Britton & Rose It is closely related to H. polyrhizus, but it has bifid stigma lobes. Le Bellec et al. (2006); Lim (2012)

H. undatus (Haw.) Britton & Rose Stems are long and green. Flowers are very long (up to 29 cm). Perianth Ariffin et al. (2009); Le Bellec (white pitaya or red pitaya with has outer green (or yellow-green) and inner white segments. Fruit is et al. (2006); Lim (2012); white flesh) rosy-red with 15–22 cm length and 300–800 g weight. It is oblong and Siddiq and Nasir (2012) covered with large and long scales, which are red and green at the tips. It has a white flesh with many small black seeds, pleasant flesh texture, and a good taste. Its fruit is slightly to significantly less sweeter than the red-fleshed pitaya fruit.

H. megalanthus (K. Schumann ex Stems are green, robust, three-ribbed, 1.5 cm thick, with slightly undu- Ariffin et al. (2009); Lim Vaupel) Ralf Bauer (syn Selenicer- lating margins, white areoles bearing 1–3 yellowish spines, 2–3mm (2012); Siddiq and Nasir eus megalanthus) (yellow pitaya) long. Flowers are nocturnal, large, white, and funnel-shaped, 32–38 cm (2012) long. Perianth has outer green and inner white segments. Stigma is lobed and green in color. Fruit is ovoid, tuberculate, spiny, yellow with numerous black seeds embedded in a sweet, juicy white pulp, and much smaller than the redpitaya. It is the sweetest varieties, with relatively smaller sized fruits.

H. purpusii (Weing.) Britton & Rose Flower is 25 cm long with margins. Le Bellec et al. (2006) Perianth has more or less reddish outer, golden middle, and white inner segments. Fruit is oblong covered with large scales. It is 10–15 cm in length and 150–400 g in weight. It has red flesh with many small black seeds, and pleasant flesh texture, but not very pronounced.

H. ocamponis (S.D.) Britton & Rose It is closely related to H. purpusii. They can be distinguished only by the Le Bellec et al. (2006) acicular and slender spines of H. ocamponis.

H. costaricensis (Web.) Britton & Stems are waxy white. Flower is nearly the same as H. polyrhizus. Fruit is Le Bellec et al. (2006) Rose 10–15 cm in diameter and 250–600 g in weight. It is ovoid and covered with scales with different size. It has a red purple flesh with many small black seeds, pleasant flesh texture and good taste.

H. trigonus (Haw.) Saff Stem is slender, green with margins, not horny. Fruit is red, ovoid or Le Bellec et al. (2006) oblong, becoming nearly smooth. It is 7–9 cm in diameter and 120– 250 g in weight. It has white flesh with many small black seeds and pleasant flesh texture, but not a very pronounced flavor. antimicrobial, hepato-protective, antihyperlipidemic, antidiabetic, and 5-cedranone (73.05%), representing 91.15% of the total oil composi- wound healing. Extensive studies of the chemical components of Hylo- tion (Ismail, Abdel-Aziz, Ghareeb, & Hassan, 2017). Celis, Gil, and Pino cereus have led to the identification of different compounds as betalains, (2012) identified 121 volatiles from H. megalanthus, consisting of alco- flavonoids, phenolic acids, triterpenes, sterols, and fatty acids. In this hols, terpenes, paraffin’s, acids, esters, ketones and other miscellaneous review, botanical characterization (Table 1), chemical constituents iso- compounds utilizing solvent extraction and subsequent concentration lated over the past few decades, nutritional importance, biological activ- (Celis et al., 2012). Then, they carried out aroma extract dilution analy- ities, and safety of the genus Hylocereus are reviewed (Figures 2–15; sis (AEDA) to identify nine odor-active compounds that could poten- Tables 2–4). Also, biosynthetic pathways of betalains have been tially influence flavor (Celis et al., 2012). Obenland et al. (2016) using discussed. solid phase micro-extraction (SPME), identified nineteen aroma volatiles from six varieties of Hylocereus (Cebra, Rosa, Lisa, San Ignacio, Mexicana, and Physical Graffiti) grown in California, including alde- 2 | CHEMICAL CONSTITUENTS hydes, alcohols, ketones, and hydrocarbons. It is noteworthy that alde- hydes constituted more than 90% of the total volatile amount Genus Hylocereus is a rich source of various classes of natural constitu- (Obenland et al., 2016). The observed differences between the two ents with diverse structural types as betalains, flavonoids, phenolic previous studies could be due to the differences in the analyzed pita- acids, terpenes, sterols, and fatty acids. The GC-MS analysis of H. poly- haya tissues and the used extraction methods (Obenland et al., 2016). rhizus stem MeOH extract revealed the existence of four major compo- In the present work, we have summarized the chemical constituents nents: terpinolene (3.69%), eucalyptol (6.54%), b-selinene (7.25%), and that have been characterized in the literature from Hylocereus sp. over 4of29 | IBRAHIM ET AL.

FIGURE 2 Biosynthetic pathways of betalains the past few decades and provided a summary of their biological prop- Enciso, & Pena-Beltran, 2012). The details of their biological activities erties, structures, molecular weights, molecular formulae, source, and had been discussed in previous reviews (Gandía-Herrero, Escribano, & associated references (Figures 2–15; Tables 2–4). Garcìa-Carmona, 2016; Khan, 2016).

2.1 | Betalains 2.2 | Biosynthesis of betalains

Betalains are a class of hydrophilic nitrogen-containing pigments, which They are derived from the L-tyrosine amino acid that is assumed to be have been reported from genus Hylocereus, especially from red pitaya. originated from arogenic acid in plants (Chung et al., 2015). There are They are divided into betaxanthins (yellow-orange pigments) and beta- three main enzymes involved in the biosynthesis of betalains: 4,5-DOPA- cyanins (red-violet pigments). They are capable of absorbing radiation extradiol-dioxygenase, tyrosinase, and betanidin-glucosyltransferase. in the visible range between 476 and 600 nm. In contrast to anthocya- Betalamic acid is the chromophore of all betalains and the basic structure nins, betalains have carboxyl functional groups instead of hydroxyl for betalains biosynthesis. The biosynthetic pathway of betalains started functional groups (Al-Alwani, Mohamad, Kadhum, & Ludin, 2015). Beta- with the conversion L-tyrosine to L-DOPA (dopamine) by hydroxylation nins possessed a wide range of biological activities as antioxidant, anti- through the tyrosinase enzyme (or polyphenoloxidase) (Figures 16 and inflammatory, hypoglycemic, antiproliferative, cardioactive, radiopro- 17). The extradiol cleavage of L-DOPA to produce 4,5-seco-DOPA tective, neuroprotective, diuretic, hypolipidemic, and osteoarthritis pain (an intermediate) was catalyzed by 4,5-DOPA extradiol-dioxygenase reliever (Esatbeyoglu et al., 2014; Khan, 2016; Lugo-Radillo, Delgado- (Sunnadeniya et al., 2016). Betalamic acid could be produced from IBRAHIM ET AL. | 5of29

FIGURE 3 Biosynthetic pathways of betalains continued

4,5-seco-DOPA by the spontaneous intra-molecular condensation the reduction of DOPA-quinone molecule back to L-DOPA. Furthermore, between the enzymatically produced aldehyde group and the amino DOPA-chrome will emerge to produce the brown polymers, character- group in L-DOPA. A variety of betalains have been formed by incorporat- izing the enzymatic browning (Toivonen & Brummell, 2008). When ing a betalamic acid unit in their structures. Betaxanthins are obtained by DOPA-chrome reacted with a reducing agent, it transformed back to spontaneous condensation reaction between the betalamic acid’salde- leuko-DOPA-chrome. Also, betanidin can be obtained from dopaxan- hyde group and the amino group of an amine to produce the correspond- thin and tyrosine-betaxanthin. Tyrosine-betaxanthin is produced by ing imine (Schliemann, Kobayashi, & Strack, 1999). Due to the variation the condensation of betalamic acid with L-tyrosine. Tyrosine- of the available amines in plants, it is difficult to determine the actual betaxanthin and dopaxanthin are turned into dopaxanthin and number of plausible betaxanthins in nature. L-DOPA is transformed to dopaxanthin-quinone, respectively, by the action of tyrosinase O-DOPA-quinone by tyrosinase in the lack of a reducing agent using (Gandía-Herrero et al., 2007). If dopaxanthin is to be maintained in molecular oxygen (Chung et al., 2015). In presence of AA or reducing the existence of tyrosinase, a reducing agent is required to change agent, O-DOPA-quinone is converted back into L-DOPA (Gandía- the O-quinone to the initial pigment. An intra-molecular nucleophilic Herrero, Escribano, & García-Carmona, 2007). Then, the amino group of attack causes cyclization of dopaxanthin-quinone to betanidin in the the O-quinone undergoes an intra-molecular nucleophilic attack on the absence of a reducing agent. Cyclo-DOPA has been proposed to react ring. This leads to the formation of leuko-DOPA-chrome (cyclo-DOPA) with betalamic acid to produce betanidin, which is the key intermedi- by spontaneous cyclization (Harris et al., 2012). Also, the conversion of ate in the production of betacyanins (Schliemann et al., 1999) (Figures

L-DOPA into cyclo-DOPA can be carried out by a cytochrome P450 16 and 17). The condensation of L-DOPA with betalamic acid pro- (Hatlestad et al., 2012). Due to leuko-DOPA-chrome’s instability, it duces dopaxanthin. Betanidin-5-O-glucosyltransferase converts betani- undergoes spontaneous oxidation to DOPA-chrome accompanying with din into betanin by incorporating a glucose moiety to the 5-hydroxyl 6of29 | IBRAHIM ET AL.

FIGURE 4 Chemical structures of betalains (1–8)isolatedformHylocereus species group (Sakuta, 2014). Conversion of betanin back to betanidin is pos- 3 | NUTRITIONAL IMPORTANCE sible due to the b-glucosidase activity (Zakharova & Petrova, 2000). Also, it has been proposed that betanin is produced by the action of Hylocereus polyrhizus is known as a wealthy source of minerals (e.g., a5-O-cyclo-DOPA glucosyltransferase that stimulates the transmission potassium, sodium, phosphorus, iron, and calcium), vitamins (e.g., B1, of sugar to cyclo-DOPA and subsequent condensation of the resulted B2, B3, and C), betacyanins, protein, carbohydrate, fat, fiber, flavonoids, glucoside with betalamic acid. The formation of betanidin-quinone is polyphenols, phytoalbumin, and carotenes (Le Bellec, Vaillant, & Imbert, achieved from betanidin by tyrosinase enzyme. Ascorbic acid converts 2006). Jaafar et al. (2009) have stated that the nutritional composition betanidin-quinone to betanidin (Gandía-Herrero et al., 2007). The of H. polyrhizus is protein (0.159–0.229 g), moisture (82.5–83 g), fat remaining hydroxyl group of betanin can be oxidized by peroxidase (0.21–0.61 g), vitamin C (8–9 mg/L), and crude fiber (0.7–0.9 g) (Jaafar enzyme into betanin phenoxy radical (Gandía-Herrero & Gandía- et al., 2009). Whereas, each 100 g of H. undatus contains protein Carmona, 2013). (1.1 g), fat (0.57 g), sorbitol (32.7 mg), vitamin C (3 mg), fiber (11.34 g), IBRAHIM ET AL. | 7of29

FIGURE 5 Chemical structures of betalains (9–14)isolatedformHylocereus species

Ca (10.2 mg), P (27.5 mg), Mg (38.9 mg), K (3.37 mg), Fe (0.7 mg), Na Aminah, Noriham, and WanAida (2010) stated that the seeds are weal- (8.9 mg), Zn (0.35 mg), fructose (3.2 mg), niacin (2.8 mg), b-carotene thy source of antioxidant and EFA with marked level of linoleic acid: (1.4 mg), lycopene (3.4 mg), and vitamin E (0.26 mg) (Arevalo-Galarza & H. megalantus (660 g/kg), H. undatus (540 g/kg), and H. polyrhizus Ortiz-Hernandez, 2004; Charoensiri, Kongkachuichai, Suknicom, & (480 g/kg) (Chemah et al., 2010). Ariffin et al. (2009) stated that the Sungpuag, 2009; FAMA, 2006). Moreover, H. megalanthus fruit per concentration of linoleic acid in Hylocereus seeds is greater than that in 100 g edible portion contains water (85%), fat (0.1 g), energy (50 cal), canola, linseed, sesame or grapevine (Ariffin et al., 2009). Lim et al. protein (0.4 g), carbohydrate (13.2 g), fiber (0.5 g), P (16 mg), Ca (2010) reported that H. undatus and H. polyrhizus seeds have a high (10 mg), Fe (0.3 mg), niacin (0.2 mg), and vitamin C (4 mg) (ICBF, 1992). quantity of oil (18.33–28.37%) (Lim et al., 2010). Also, their total con- It is noteworthy that the high fiber content of different Pitahaya fruits tents of tocopherol were 36.7 and 43.5 mg/100 g, respectively (Lim increases stool volume and protects from cancer. Hylocereus seeds oils et al., 2010). These studies showed that pitaya’s seed oil has a high per- have earned attention due to their health significance which is related cent of functional lipids and could be a new source of essential oil. to their comparatively high composition of endogenous antioxidants as Wichienchot, Jatupornpipat, and Rastall (2010) reported that H. unda- phenolics, tocopherols, and essential fatty acids (EFA) (Lim et al., 2010). tus and H. polyrhizus pulps have glucose, fructose, and oligosaccharides Ariffin et al. (2009) mentioned that linoleic and linolenic acids com- of different molecular weights, representing 86.2 and 89.6 g/kg, prised a considerable proportion of the unsaturated fatty acids of H. respectively, total concentrations (Wichienchot et al., 2010). In yogurt, undatus and H. polyrhizus seed oil extracts (Ariffin et al., 2009). They H. undatus or H. polyrhizus pulp addition augmented lactic acid content, contained about 50% EFA, in which linoleic acid is in a greater ratio milk fermentation rates, total phenolic content, and antioxidant activity than linolenic (48% C18:2 and 1.5% C18:3). In other study, Chemah, (Zainoldin & Baba, 2012). 8of29 | IBRAHIM ET AL.

FIGURE 6 Chemical structures of betalains (15–20)isolatedformHylocereus species

| 4 BIOLOGICAL ACTIVITIES antioxidative potential. Phenolics are abundant components of the plant that are primarily originated from phenylalanine through the phe- | 4.1 Antioxidant activities nyl propanoid pathway (Hollman, Hertog, & Katan, 1996). Phytonutrients are the secondary metabolites of plant origin, which Choo and Yong (2011) reported that the antiradical potential of H. have health-boosting properties. The prominence of the antioxidant polyrhizus pulps and fruits peels (IC50s 9.93 and 11.34 mg/mL, respec- constituents in maintaining health and protecting from cancer and cor- tively) was higher than those of H. undatus peels and pulps (IC50s14.61 onary heart disease is raising a significant interest among consumers, and 9.91 mg/mL, respectively) in DPPH assay. These results were food manufacturers, and scientists. Accordingly, the future’strendis attributed to their contents of polyphenols and ascorbic acid (Choo & directed to the functional food with particular health effects. In vitro Yong, 2011). Five different Costa Rican genotypes of Hylocereus sp. researches referred that phytonutrients as phenolic compounds may (Lisa, Orejona, Rosa, Nacional, and San Ignacio) and H. polyrhizus fruits possess a significant role, in addition to vitamins in the biological sys- were evaluated for their antioxidant effects using TEAC assay. Lisa, tems protection from the serious effects of oxidative stress (Kalt, Nacional, and H. polyrhizus exhibited maximum TEAC values 36.1, 34.8, 2005). Polyphenols or phenolics have gained a great attention due to and 30.5 mg/100 mL, respectively. While the remaining genotypes their physiological effects: antimutagenic, antioxidant, and antitumor. showed lower TEAC values. The significant difference observed They have been cited to be a powerful opponent to resist free radicals, between different genotypes was attributed to the difference in beta- which are harmful to our foods systems and body (Nagai, Reiji, Hachiro, lains contents and their composition in the different types (Esquivel, & Nobutaka, 2003). Although phenolics do not have any nutritional Stintzing, & Carle, 2007). Halimoon and Abdul Hasan (2010) reported value, they may be fundamental to human health due to their that the ethanolic extract of H. undatus exhibited the highest IBRAHIM ET AL. | 9of29

FIGURE 7 Chemical structures of betalains (21–26)isolatedformHylocereus species scavenging activity (63.44%) of DPPH compared to the aqueous Moreover, the MeOH extract of H. polyrhizus stem had antioxidant (55.04%) and MeOH extracts (8.82%) (Halimoon & Abdul Hasan, effect with TAC (total antioxidant capacity) value 726.73 mg AAE/g 2010). dry extract using phosphomolybdenum method (Ismail et al., 2017). Khalili et al. (2009) mentioned that red pitaya extract showed Tze et al. (2012) stated that the H. polyrhizus fruit powder exhibited potent antioxidant activities with 76.10 and 72.9% in the FTC and TBA antioxidant activity with an IC50 value of 2.25 mg/L in the DPPH assay assays, respectively (Khalili et al., 2009). Moreover, the supercritical (Tze et al., 2012). The fruit flesh and peels extracts of H. polyrhizus

CO2 peel extracts of H. undatus and H. polyrhizus exhibited antioxidant fruits exhibited the highest radical scavenging and reducing potentials activities with IC50 values of 0.91 and 0.83 mg/mL, respectively (Luo, in DPPH and FRAP assays, respectively, due to their high betacyanin Cai, Peng, Liu, & Yang, 2014). The ethanolic extract of H. undatus fruit contents. The results referred that the flesh is a substantial source of peel exhibited antioxidant activity with an IC50 value of 0.084 mg/mL antioxidants with health benefits for human diet and peels as a valuable in DPPH and TEAC value of 0.685 mM/mg in ABTS assay (Okonogi, manufacture by-product to be exploited for the formulation of nutra- Duangrat, Anuchpreeda, Tachakittirungrod, & Chowwanapoonpohn, ceuticals and food applications (Tenore, Novellino, & Basile, 2012). 2007). Moreover, H. undatus juice at volumes 50–200 mLpossessed The peels and flesh extracts of H. polyrhizus fruits exhibited antiox- antioxidant activity range from 18.5 to 30% using DPPH assay com- idant activities with IC50 values of 118 and 22.4 mMvitaminCequiva- pared to ascorbic acid (Sudha, Baskaran, Ramasamy, & Siddharth, lents/g for the DPPH assay and 28.3 and 175 mM TEAC/g for ABTS 2017). The pectin from dragon fruit peels had high antioxidant poten- assay, respectively (Wu et al., 2006). The MeOH extract of H. undatus tial with IC50s0.0063–0.0080 mg/mL compared to ascorbic acid (IC50 exhibited strong antioxidant activity with an IC50 193 lg/mL (Elfi 0.00502 mg/mL) (Zaidel, Rashid, Hamidon, Salleh, & Kassim, 2017). Susanti et al., 2012). This variation in the observed results of the 10 of 29 | IBRAHIM ET AL.

FIGURE 8 Chemical structures of betalains (27–34)isolatedformHylocereus species antioxidant activity may be attributed to geographical and seasonal var- values of 3.31, 2.83, and 10.70 mol-TEA/mol, respectively. In addition, iations. Also, quantitative and qualitative variations in the phenolics, they exhibited nitrogen radical scavenging activity with IC50s17.51, betalains, and ascorbic acid contents between different species of Hylo- 6.81, and 24.48 mM, respectively. These results indicated that these cereus and within the genotypes of the same species have been betacyanins will be beneficial as natural pigments to give defense reported (Esquivel et al., 2007; Lim et al., 2010). against oxidative stress (Taira, Tsuchida, Katoh, Uehara, & Ogi, 2015). Compounds 2, 6,and61 isolated from H. polyrhizus exhibited a Compound 2 exhibited a dose-dependent scavenging potential of galvi- dose-dependent peroxyl radical scavenging capacity in concentration noxyl, DPPH, hydroxyl, and superoxide radicals in the spin trapping and range 25–100 nM. Also, they showed antioxidant capacities with TEAC electron spin resonance spectroscopy (ESR) studies. Also, it prohibited IBRAHIM ET AL. | 11 of 29

FIGURE 9 Chemical structures of betalains (35–40)isolatedformHylocereus species

H2O2 produced DNA damage of HT-29 cell using Comet assay at dose 55.2 and 78.9%, respectively, at 0.7 mg/mL compared to ADM (% inhibi- 15 lM. Furthermore, the treatment of Huh7 cells with 2 (15 lM) tions 97.2, 99.3, and 98.1, respectively, at 0.1 mg/mL). Moreover, they stimulated the transcription factor Nrf2 and led to the rise of PON1 showed concentration-dependent antiproliferative effects with IC50 val- transactivation, HO-1 protein levels, and cellular GSH. So, 2 acted as ues 0.61 and 0.64, 0.45 and 0.47, and 0.43 and 0.73 mg/mL, respectively, an inducer of endogenous cellular enzymatic antioxidant defense toward the three tested cancer cell lines. It is noteworthy that the inhibi- mechanisms and as a free radical scavenger (Esatbeyoglu et al., 2014; tory potential of H. polyrhizus was stronger than that of H. undatus partic- Sakihama, Maeda, Hashimoto, Tahara, & Hashidoko, 2012). It was ularly toward MGC-803 cells. These activities of the pitaya peel extracts reported that betacyanins as betanin, betanidin, betanidin, and phyllo- were extremely possibly due to the presence of pentacyclic triterpenoids cactin act as strong reducing agents (Khan, 2016). andsteroids,whichhavebeenknowntopossessanticanceractivities (Luo et al., 2014). The H. polyrhizus stem MeOH extract exhibited in vitro 4.2 | Anticancer activities cytotoxic activity toward breast (MCF-7) and liver (HepG-2) carcinoma m Polyphenolics, betalains, unsaturated fats, vitamins, minerals, and toco- with IC50s2.8and4.2 g, respectively, using sulphorhodamine-B (SRB) pherols commonly found in pitahaya fruits give chemo-protective assay (Ismail et al., 2017). Compounds 99, 100,and106 isolated from H. potentials to counter the oxidative stress and keep balance among anti- polyrhizus and H. undatus peels exhibited cytotoxicity toward Bcap-37, oxidants and oxidants to make human health effects. An imbalance PC3, and MGC-803 cells with IC50 values of 65.4, 74.4, and 73.2, 79.3, caused by excess oxidants leads oxidative stress, resulting in damage of 58.2, and 78.4, and 56.9, 43.8, and 51.9 mM, respectively. While, com- > m protein and DNA and increasing the hazard of degenerative diseases as pound 105 was found to be less active with an IC50 100 Mcompared cancer (Luo et al., 2014; Wu et al., 2006). to ADM (IC50s 1.09, 1.34, and 0.83 mM, respectively) (Luo et al., 2014).

The supercritical CO2 peel extracts of H. undatus and H. polyrhizus The peel extract of H. polyrhizus exhibited stronger antiproliferative activ- exhibited cytotoxic activities toward Bcap-37, PC3, and MGC-803 cancer ity than its flesh extract toward B16F10 melanoma cells with an IC50 cell lines with inhibitory ratios of 62.4 and 63.5%, 60.7 and 67.3%, and 25.0 mg of peel matter (Wu et al., 2006). 12 of 29 | IBRAHIM ET AL.

FIGURE 10 Chemical structures of betalains (41–46) isolated form Hylocereus species

4.3 | Antimicrobial activities skin disorders. It is noteworthy that the polyphenolic fractions showed a broad antimicrobial spectrum toward all human pathogenic and/or The antibacterial activities of the EtOH, CHCl , and hexane extracts of 3 food spoilage bacteria (B. cereus, E. faecalis, S. aureus, L. monocytogenes, H. polyrhizus and H. undatus peels were evaluated toward Bacillus cer- E. coli, Salmonella typhi Ty2, Proteus mirabilis, Proteus vulgaris, Pseudomo- eus, Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, nas aeruginosa, Y. enterocolitica, Enterobacter cloacae, K. pneumonia,and Salmonella typhimurium, Escherichia coli, Yersinia enterocolitica, Klebsiella Enterobacter aerogenes), moulds (Fusarium oxysporum, Botrytis cinerea, pneumonia,andCampylobacter jejuni using disc diffusion and broth Cladosporium herbarum,andAspergillus flavus (ATCC 15517),andyeasts micro-dilution methods. The results showed that the chloroform (Candida albicans and Rhizoctonia solani). However, the nonfractionated extract exhibited good antibacterial activity toward all tested patho- extracts revealed a very low or no activity (Tenore et al., 2012). The gens. In addition, all extracts prohibited the growth of all bacteria with acetone extract (conc. 70%) of Hylocereus peel had a high antibacterial MICs in the range of 1.25–10.0 mg/mL (Nurmahani, Osman, Abdul effect toward Salmonella typhi using agar diffusion assay (Escobar, Hamid, Mohamad, & Pak, 2012). Gomez, Bautista, & Perez, 2010). These studies mentioned that beta- The in vitro antimicrobial potential of the extracts and fractions cyanins, flavonoids, phenolic acids, tannins, and terpenoids might be from the flesh and peels of H. polyrhizus was evaluated toward two responsible compounds for the antimicrobial activity (Nurmahani et al., yeasts, four molds, and 13 bacteria species, which are known to be 2012; Tenore et al., 2012). The stem MeOH extract of H. polyrhizus foodborne pathogens causing gastrointestinal, respiratory, urinary, and possessed strong antimicrobial activity against S. aureus, P. aeruginosa, IBRAHIM ET AL. | 13 of 29

FIGURE 11 Chemical structures of betalains (47–54) isolated form Hylocereus species

C. albicans, Aspergillus niger, and F. oxysporum with inhibition zones 29, and fruits (5–7 serving/day) decreases the incidence of coronary heart 29, 29.5, 17.5, and 29.5 mm and 9.5, 11, 10, 8, and 16.5 mm, respec- disease, attenuates the insulin resistance and dyslipidemia, and pre- tively, using cup agar and disk diffusion methods, respectively (Ismail vents atherosclerosis (Omidizadeh, 2009; Wybraniec et al., 2001). It is et al., 2017). believed that these effects could be produced through the useful com- bination of antioxidants, micronutrients, fiber, and phytochemical contents in food (Wybraniec et al., 2001). 4.4 | Antihyperlipidemic and antidiabetic activities Daily oral administration of 1.17, 0.87, and 0.5% red pitaya to rat Consumption of vegetables and fruits lessen the incidence of cancer feed with cholesterol-rich diet showed a significant reduction in the and cardiovascular diseases (Stintzing, Schieber, & Carle, 2002). total plasma cholesterol levels (59.06, 56.72, and 49.14%, respectively) Wybraniec et al. (2001) suggested that the high ingestion of vegetables after 5 weeks of supplementation. Moreover, it had potential in 14 of 29 | IBRAHIM ET AL.

FIGURE 12 Chemical structures of betalains (55–69) isolated form Hylocereus species

increasing HDL-C and decreasing LDL-C and TG levels. Thus, the food diabetic individuals (Wichienchot et al., 2010). Consumption of red pit- supplementation of red pitaya may be helpful in the prohibition of dys- aya attenuated dyslipidemia and insulin resistance caused by HFD in lipidemia and cardiovascular disease (Khalili et al., 2009). Stintzing et al. rats (Omidizadeh, 2009). It was reported that the fresh H. polyrhizus (2002) stated that the mucilage from the pulp of H. polyrhizus exerted a fruit juice significantly reduced the hypertriglyceridemia, insulin resist- positive influence on cholesterol metabolism (Stintzing et al., 2002). It ance, and atherosclerotic changes caused by fructose supplement in was reported that oligosaccharides obtained from white-flesh dragon rats. Its anti-insulin resistant effect could be referred to its polyphenols, fruit decreased insulinemia and caloric intake in comparison to digested soluble dietary fiber, and antioxidant contents. Moreover, the antioxi- carbohydrates. Therefore, they may be appropriate for inclusion as dant content is fundamental to improve dyslipidemia and atherogenesis food supplements in the products designed for the overweight and in insulin-resistant rats. In addition, the soluble dietary fiber sole could IBRAHIM ET AL. | 15 of 29

FIGURE 13 Chemical structures of phenolic compounds (70–79) isolated form Hylocereus species not reverse independently the hyper-insulinemia side effects (Omidizadeh 4.6 | Anti-anemia and anti-inflammatory activities et al., 2014). Sudha et al. (2017) reported that white dragon fruit juice Widyaningsih, Setiyani, Umaroh, Sofro, and Amri (2017) stated that the had a-amylase inhibitory activity ranging from 1.033 to 32.436% at conc. red dragon fruit juice had significant effect on pregnant women’s 25–100 mL using starch-agar gel diffusion assay (Sudha et al., 2017). hemoglobin and erythrocyte levels in the seventh day of intervention Also, the lipase inhibitory capacity of H. undatus juice was assessed and had no effect on hemoglobin and erythrocyte levels in the 14th using a Rhodamine agar plate assay. The results revealed that the day of intervention (Widyaningsih et al., 2017). Thus, its juice can be an juice (conc. 25–100 mL) exhibited antilipase activity 6.125–46.939% alternative treatment for pregnant women’s anemia. The red dragon (Sudha et al., 2017). fruit rind extract at doses 0.25–1mg/gbodyweightdecreased interleukin-1b (IL-1b) level, vascular endothelial growth factor (VEGF) 4.5 | Wound healing activities expression, and endometriosis in mice via decreasing nuclear factor- Application of the aqueous extracts of the leaves and flowers of H. jappa beta (NF-jB) activity (Eka, Hendarto, & Widjiati, 2017). undatus topically in wounded-diabetic rats produced a significant wound healing activity. While the fruit pulp aqueous extract had 4.7 | Micro-vascular protective activities less activity. H. undatus caused increase in the tensile strength, hydroxyproline, DNA collagen content, total proteins, and better Compounds 103 and 104 isolated from H. undatus leaves possessed epithelization thereby facilitating healing. This plant property vali- protective effects toward the skin vascular permeability increase in rab- dated its uses for the treatment of injuries in traditional medicine bits. They showed 53.5 and 70.1% reduction in the leakage of Evans (Perez, Vargas, & Ortiz, 2005). blue, respectively, at 50 mg/kg compared to troxerutin (64.5%) at the 16 of 29 | IBRAHIM ET AL.

4.9 | Prebiotic effects

White-flesh dragon fruit’s oligosaccharides showed prebiotic effects. They were used as a carbon source for the cultivation of two probiotic strains: Lactobacillus delbrueckii BCC13296 and Bifidobacterium bifidum NCIMB 702715. They stimulated their growth by increasing their num- bers from 9.02 3 107 to 6.17 3 109 cell/mL within 48 hr for L. delbrueckii and from 1.70 3 108 to 2.51 3 109 cell/mL within 72 hr for B. bifidum (Thammarutwasik et al., 2009).

5 | ROLES OF HYLOCEREUS IN FOOD INDUSTRY

People usually consume dragon fruits directly or processed into juice. Therefore, the peel is the main byproduct of dragon fruits. The pectic-like substance of H. polyrhizus peelandmesocarpcouldbe used in the food manufacture as a thickening agent (Stintzing et al., 2002). The aqueous extract of mesocarp and the pulp juice of H. polyrhizus could act as a coloring agent for low acid food commodities (Stintzing & Carle, 2004; Stintzing et al., 2002). Tze et al. (2012) reported that the pitaya fruit powder produced from whole pitaya fruit has potential to use as a natural coloring agent and a health supplement (Tze et al., 2012). Also, white-flesh dragon fruit oligosaccharides have been included as food supplements in various food products, for example, prebiotic and dairy products (Wichienchot

FIGURE 14 Chemical structures of phenolic compounds (80–95) et al., 2010). Furthermore, the addition of red and white dragon isolated form Hylocereus species fruits into yogurt enhanced the lactic acid content, milk fermentation rate, antioxidant activity, and total phenolics content in yogurt same doses. The results indicated that they increased capillary resist- (Zainoldin & Baba, 2009). The betalains, fruit pigments from red ance and reduced permeability (Gutierrez et al., 2007). dragon fruit are utilized as natural food colorants in different areas of the food manufacturing (Choo & Yong, 2011). In pharmaceutical 4.8 | Hepato-protective activities industries, the amylase enzyme encapsulated in Arabic gum-chitosan matrix hold complete bio-catalytic effect and possessed a consider- The methanolic extract of H. polyrhizus fruits at 300 mg/kg body able rise in the pH and temperature stabilities in comparison to the weight exhibited significant protection of the liver against CCl4 free enzyme (Amid, Manap, & Zohdi, 2014). Additionally, the peels induced hepatotoxicity in rats compared to silymarin. The results could be a substantial source of novel pectinases for using in a vari- indicated that the oral intake of H. polyrhizus fruits extract promoted ety of industrial and biotechnological implementations due to their the defense status toward liver injury. The effect was due to the broad specificity to substrate with high stability under overdone phenolics and tocopherols contents which have a strong effect in conditions. Also, pitaya peel could be utilized as a rich and cost- reducing the oxidative stress that enhances the cardiac and nephro- efficient source for producing valuable types of enzymes, which logical damages including hepatic injury (Islam et al., 2013). Ramli, have a wide range of uses in beverage, fruit, and textile industries, Brown, Ismail, and Rahmat (2014) reported that red pitaya juice sup- paper and pulp making, and tea and coffee fermentation (Zohdi & plementation for 8 weeks decreased ALT and ALP but gave rise to a Amid, 2013). significant increase in AST in rats fed with a high-carbohydrate and HFD (Ramli et al., 2014). This provides scientific evidence that the 6 | ECONOMY OF HYLOCEREUS juice of red pitaya may provide a protection toward the damage of SP. PRODUCTION the liver, which could be attributed to the presence of multiple bioactive compounds which may act synergistically. The consumption Hylocereus is among the most important commercial tropical fruits of red pitaya supplemented diet prevents or treats the paracetamol in the World (Lim et al., 2010). A great attention has been given to induced hepatotoxicity in rats and other associated deleterious it due to the promising high net profit depending on growing effects. This hepato-protective potential could be related to poly- Asian-United State population. Its known health significances linked phenols, flavonoids, alkaloids, amino acids, steroids, and vitamins to its potential antioxidant capacities. However, its publicity at (Ramli et al., 2014). high-end restaurants is because of its unequaled taste, prettiness, IBRAHIM ET AL. | 17 of 29

FIGURE 15 Chemical structures of sterols and terpenes (96–110) isolated form Hylocereus species

TABLE 2 List of betalains isolated from Hylocereus species

Compound Molecular Molecular No. name Source formula weight Reference

1 Betanidin 5-O-b-so- Fruit of H. polyrhizus, H. ocam- C30H37N2 O18 713 Wybraniec, Nowak-Wydra, Mitka, phoroside ponis, H. undatus Kowalski, and Mizrahi (2007) Fruit of H. polyrhizus Tenore et al. (2012); Wybraniec et al. (2009) Fruits of Hylocereus sp. geno- Esquivel et al. (2007) types: Lisa, Nacional, Orejo- na, Rosa, and San Ignacio Mesocarp of H. polyrhizus Stintzing et al. (2002)

2 Betanin Fruit of H. polyrhizus, H. ocam- C24H27N2 O13 551 Wybraniec et al. (2007) ponis, H. undatus Fruits of H. polyrhizus, H. undatus, H. costaricensis, H. purpusi Fruit of H. polyrhizus Stintzing, Conrad, Klaiber, Beifuss, and Carle (2004); Taira et al. (2015); Tenore et al. (2012); Wy- braniec and Mizrahi (2004); Wy- braniec et al. (2009); Wybraniec, Nowak-Wydra, and Mizrahi (2006) Fruits of Hylocereus sp. geno- Esquivel et al. (2007) types: Lisa, Nacional, Orejo- na, Rosa, and San Ignacio (Continues) 18 of 29 | IBRAHIM ET AL.

TABLE 2 (Continued)

Compound Molecular Molecular No. name Source formula weight Reference Mesocarp of H. polyrhizus Stintzing et al. (2002) Fruit pulp of H. polyrhizus Wybraniec et al. (2001) Juice of H. polyrhizus Herbach, Stintzing, and Carle (2004, 2005)

3 Isobetanin Fruit of H. polyrhizus, H. ocam- C24H27N2 O13 551 Wybraniec et al. (2007) ponis, H. undatus Fruits of H. polyrhizus, H. undatus, H. costaricensis, H. purpusi Fruit of H. polyrhizus Stintzing et al. (2004); Taira et al. (2015); Tenore et al. (2012); Wybraniec and Mizrahi (2004); Wybraniec et al. (2006, 2009) Fruits of Hylocereus sp. geno- Esquivel et al. (2007) types: Lisa, Nacional, Orejo- na, Rosa, and San Ignacio Mesocarp of H. polyrhizus Stintzing et al. (2002) Fruit pulp of H. polyrhizus Wybraniec et al. (2001) Juice of H. polyrhizus Herbach et al. (2004, 2005)

0 42-O-Apiosyl-betanin Fruit of H. polyrhizus, H. ocam- C29H35N2 O17 683 Wybraniec et al. (2007) ponis, H. undatus Fruit of H. polyrhizus Wybraniec et al. (2009) Fruits of Hylocereus. sp. geno- Esquivel et al. (2007) types: Lisa, Nacional, Orejona, Rosa, and San Ignacio

0 52-O-Apiosyl-isobeta- Fruit of H. polyrhizus, H. ocam- C29H35N2 O17 683 Wybraniec et al. (2007) nin ponis, H. undatus Fruit of H. polyrhizus Wybraniec et al. (2009) Fruits of Hylocereus sp. geno- Esquivel et al. (2007) types: Lisa, Nacional, Orejo- na, Rosa, and San Ignacio

6 Phyllocactin Fruit of H. polyrhizus, H. ocam- C27H29N2 O16 637 Wybraniec et al. (2007) ponis, H. undatus Fruits of H. polyrhizus, H. undatus, H. costaricensis, H. purpusi Fruit of H. polyrhizus Stintzing et al. (2004); Taira et al. (2015); Tenore et al. (2012); Wybraniec and Mizrahi (2004); Wybraniec et al. (2009) Fruits of Hylocereus sp. geno- Esquivel et al. (2007) types: Lisa, Nacional, Orejo- na, Rosa, and San Ignacio Mesocarp of H. polyrhizus Stintzing et al. (2002) Fruit pulp of H. polyrhizus Wybraniec et al. (2001) Juice of H. polyrhizus Herbach et al. (2004, 2005)

7 Isophyllocactin Fruit of H. polyrhizus, H. ocam- C27H29N2 O16 637 Wybraniec et al. (2007) ponis, H. undatus Fruits of H. polyrhizus, H. undatus, H. costaricensis, H. purpusi Fruit of H. polyrhizus Stintzing et al. (2004); Tenore et al. (2012); Wybraniec et al. (2009) Fruits of Hylocereus sp. geno- Esquivel et al. (2007) types: Lisa, Nacional, Orejo- na, Rosa, and San Ignacio Mesocarp of H. polyrhizus Stintzing et al. (2002) Fruit pulp of H. polyrhizus Wybraniec et al. (2001) Juice of H. polyrhizus Herbach et al. (2004, 2005)

0 84-Malonyl-betanin Fruit of H. polyrhizus, H. ocam- C27H29N2 O16 637 Wybraniec et al. (2007) ponis, H. undatus (Continues) IBRAHIM ET AL. | 19 of 29

TABLE 2 (Continued)

Compound Molecular Molecular No. name Source formula weight Reference Fruit of H. polyrhizus Wybraniec et al. (2009) Fruit of H. polyrhizus Tenore et al. (2012)

0 94-Malonyl-isobetanin Fruit of H. polyrhizus, H. ocam- C27H29N2 O16 637 Wybraniec et al. (2007) ponis, H. undatus Fruit of H. polyrhizus Wybraniec et al. (2009)

10 Hylocerenin Fruit of H. polyrhizus, H. ocam- C30H35N2 O17 695 Wybraniec et al. (2007) ponis, H. undatus Fruits of H. polyrhizus, H. undatus, H. costaricensis, H. purpusi Fruit of H. polyrhizus Stintzing et al. (2004); Tenore et al. (2012); Wybraniec and Mizrahi (2004); Wybraniec et al. (2009) Fruits of Hylocereus. sp. geno- Esquivel et al. (2007) types: Lisa, Nacional, Orejo- na, Rosa, and San Ignacio Mesocarp of H. polyrhizus Stintzing et al. (2002) Fruit pulp of H. polyrhizus Wybraniec et al. (2001) Juice of H. polyrhizus Herbach et al. (2004, 2005)

11 Isohylocerenin Fruit of H. polyrhizus, H. ocam- C30H35N2 O17 695 Wybraniec et al. (2007) ponis, H. undatus Fruits of H. polyrhizus, H. undatus, H. costaricensis, H. purpusi Fruit of H. polyrhizus Stintzing et al. (2004); Tenore et al. (2012); Wybraniec et al. (2009) Fruits of Hylocereus. sp. geno- Esquivel et al. (2007) types: Lisa, Nacional, Orejo- na, Rosa, and San Ignacio Mesocarp of H. polyrhizus Stintzing et al. (2002) Fruit pulp of H. polyrhizus Wybraniec et al. (2001) Juice of H. polyrhizus Herbach et al. (2004, 2005)

0 12 2 -O-Apiosyl-phyllo- Fruit of H. polyrhizus, H. ocam- C32H37N2 O20 769 Wybraniec et al. (2007) cactin ponis, H. undatus Fruit of H. polyrhizus Wybraniec et al. (2009)

0 13 2 -O-Apiosyl-isophyl- Fruit of H. polyrhizus, H. ocam- C32H37N2 O20 769 Wybraniec et al. (2007) locactin ponis, H. undatus Fruit of H. polyrhizus Wybraniec et al. (2009)

00 0 14 5 -O-E-Feruloyl-2 - Fruit of H. polyrhizus, H. ocam- C39H43N2 O20 859 Wybraniec et al. (2007) apiosyl-betanin ponis, H. undatus

00 0 15 5 -O-E-Feruloyl-2 - Fruit of H. polyrhizus, H. ocam- C39H43N2 O20 859 Wybraniec et al. (2007) apiosyl-isobetanin ponis, H. undatus

00 0 16 5 -O-E-Sinapoyl-2 - Fruit of H. polyrhizus, H. ocam- C40H45N2 O21 889 Wybraniec et al. (2007) apiosyl-betanin ponis, H. undatus

00 0 17 5 -O-E-Sinapoyl-2 - Fruit of H. polyrhizus, H. ocam- C40H45N2 O21 889 Wybraniec et al. (2007) apiosyl-isobetanin ponis, H. undatus

00 0 18 5 -O-E-Feruloyl-2 - Fruit of H. polyrhizus, H. ocam- C42H45N2 O23 945 Wybraniec et al. (2007) apiosyl-phyllocac- ponis, H. undatus tin

00 0 19 5 -O-E-Feruloyl-2 - Fruit of H. polyrhizus, H. ocam- C42H45N2 O23 945 Wybraniec et al. (2007) apiosyl-isophyllo- ponis, H. undatus cactin

20 Isobetanidin 5-O- Fruit of H. polyrhizus C30H37N2 O18 713 Wybraniec et al. (2009) b-sophoroside Fruits of Hylocereus sp. geno- Esquivel et al. (2007) types: Lisa, Nacional, Orejo- na, Rosa, and San Ignacio

(Continues) 20 of 29 | IBRAHIM ET AL.

TABLE 2 (Continued)

Compound Molecular Molecular No. name Source formula weight Reference

0 21 Betanidin-6 -O-malo- Fruit of H. polyrhizus C33H39N2 O21 799 Wybraniec et al. (2009) nyl-5-O-b- sophoroside

0 22 Isobetanidin-6 -O- Fruit of H. polyrhizus C33H39N2 O21 799 Wybraniec et al. (2009) malonyl-5-O-b-sophoroside

0 00 00 23 4 -O-(3 -Hydroxy-3 - Fruit of H. polyrhizus C30H35N2 O17 695 Wybraniec et al. (2009) methyl-glutaryl) betanin

0 00 00 24 4 -O-(3 -Hydroxy-3 - Fruit of H. polyrhizus C30H35N2 O17 695 Wybraniec et al. (2009) methyl-glutaryl) Mesocarp of H. polyrhizus Stintzing et al. (2002) isobetanin

0 25 Betanidin-5-O-(6 -O- Fruit of H. polyrhizus C28H33N2 O15 637 Esquivel et al. (2007); Tenore et al. 3-hydroxy-butyryl)- (2012) b-glucoside Mesocarp of H. polyrhizus Stintzing et al. (2002) Juice of H. polyrhizus Herbach et al. (2004)

26 2-Decarboxy-betanin Fruit of H. polyrhizus C23H27N2 O11 507 Wybraniec et al. (2006) Juice of H. polyrhizus Herbach et al. (2005)

27 17-Decarboxy-beta- Fruit of H. polyrhizus C23H27N2 O11 507 Wybraniec and Mizrahi (2004); nin Wybraniec et al. (2006) Juice of H. polyrhizus Herbach et al. (2004, 2005)

28 2,17-Bidecarboxy-be- Fruit of H. polyrhizus C22H27N2 O9 463 Wybraniec et al. (2006) tanin

29 2-Decarboxy-phyllo- Fruit of H. polyrhizus C26H29N2 O14 593 Wybraniec et al. (2006) cactin Juice of H. polyrhizus Herbach et al. (2004, 2005)

30 2,17-Bidecarboxy- Fruit of H. polyrhizus C25H29N2 O12 549 Wybraniec et al. (2006) phyllocactin Juice of H. polyrhizus Herbach et al. (2004, 2005)

31 2-Decarboxy-hylo- Fruit of H. polyrhizus C29H35N2 O15 651 Wybraniec et al. (2006) cerenin Juice of H. polyrhizus Herbach et al. (2004, 2005)

32 2,17-Bidecarboxy-hy- Fruit of H. polyrhizus C28H35N2 O13 607 Wybraniec et al. (2006) locerenin Juice of H. polyrhizus Herbach et al. (2004, 2005)

33 17-Decarboxy-isobe- Juice of H. polyrhizus C23H27N2 O11 507 Herbach et al. (2004) tanin

34 15-Decarboxy-beta- Juice of H. polyrhizus C23H27N2 O11 507 Herbach et al. (2004, 2005) nin

35 Neobetanin Fruits of Hylocereus sp. C24H25N2 O13 549 Esquivel et al. (2007) genotypes: Lisa, Nacional, Orejona, Rosa, and San Ignacio Juice of H. polyrhizus Herbach et al. (2004)

36 2-Decarboxy-neobe- Juice of H. polyrhizus C23H25N2 O11 505 Herbach et al. (2004, 2005) tanin

37 2-Decarboxy-neobe- Juice of H. polyrhizus C26H27N2 O14 591 Herbach et al. (2004, 2005) tanidin 5-O-(60-O- malonyl)-b-glucoside

38 17-Decarboxy-neo- Juice of H. polyrhizus C23H25N2 O11 505 Herbach et al. (2004, 2005) betanin

39 2,17-Bidecarboxy- Juice of H. polyrhizus C22H25N2 O9 461 Herbach et al. (2004, 2005) neobetanin (Continues) IBRAHIM ET AL. | 21 of 29

TABLE 2 (Continued)

Compound Molecular Molecular No. name Source formula weight Reference

40 2-Decarboxy-isophyl- Juice of H. polyrhizus C26H29N2 O14 593 Herbach et al. (2004) locactin

41 15-Decarboxy-hylo- Juice of H. polyrhizus C29H35N2 O15 651 Herbach et al. (2005) cerenin

42 2,17-Bidecarboxy- Juice of H. polyrhizus C25H27N2 O12 547 Herbach et al. (2004, 2005) neobetanidin 5-O- (60-O-malonyl)- b-glucoside

43 2,17-Bidecarboxy- Juice of H. polyrhizus C28H33N2 O13 605 Herbach et al. (2004) neobetanidin 5-O- (60-O-3-hydoxy-3- methyl-glutryl)- b-glucoside

44 17-Decarboxy-phyl- Fruit of H. polyrhizus C26H29N2 O14 593 Wybraniec and Mizrahi (2004); Wy- locactin braniec et al. (2006) Juice of H. polyrhizus Herbach et al. (2005)

45 17-Decarboxy-hylo- Fruit of H. polyrhizus C29H35N2 O15 651 Wybraniec and Mizrahi (2004) cerenin Juice of H. polyrhizus Herbach et al. (2005)

46 Gomphrenin I (Beta- Fruits of Hylocereus sp. geno- C24H27N2 O13 551 Esquivel et al. (2007) nidin-6-O-b-gluco- types: Lisa, Nacional, Orejo- side) na, Rosa, and San Ignacio

47 Isogomphrenin I (Iso- Fruits of Hylocereus sp. geno- C24H27N2 O13 551 Esquivel et al. (2007) betanidin-6-O- types: Lisa, Nacional, Orejo- b-glucoside) na, Rosa, and San Ignacio

48 Isobetanidin-5-O- Fruits of Hylocereus sp. geno- C28H33N2 O15 637 Esquivel et al. (2007) (60-O-3-hydroxy- types: Lisa, Nacional, Orejo- butyryl)-b-glucoside na, Rosa, and San Ignacio (Isobutyrylbetanin)

49 15-Hydroxybetani- Juice of H. polyrhizus C24H27N2 O14 567 Herbach et al. (2005) din-5-O-b-glucoside

50 15-Hydroxyisobetani- Juice of H. polyrhizus C24H27N2 O14 567 Herbach et al. (2005) din-5-O-b-glucoside

51 Neobetanidin 5-O- Juice of H. polyrhizus C22H23N 2O9 459 Herbach et al. (2005) b-glucoside, bi- decarboxylated, dehydrogenated

52 2-Decarboxy-neobe- Juice of H. polyrhizus C29H33N2 O15 649 Herbach et al. (2005) tanidin 5-O-(60-O- 3-hydoxy-3- methyl-glutryl)- b-glucoside

53 2,15,17-Tridecar- Juice of H. polyrhizus C27H33N2 O11 561 Herbach et al. (2005) boxy-neobetanidin 5-O-(60-O-3-hydoxy-3-methyl-glutryl)-b-glucoside

54 15-Decarboxy-phyl- Juice of H. polyrhizus C26H29N2 O14 593 Herbach et al. (2005) locactin

0 55 Betanidin-5-O-(6 - Juice of H. polyrhizus C26H29N2 O14 593 Herbach et al. (2005) acetyl)-b-glucoside

56 Indicaxanthin Fruit of H. polyrhizus, H. ocam- C14H17N2 O6 309 Wybraniec et al. (2007) ponis, H. undatus Fruit of H. polyrhizus Wybraniec et al. (2009)

(Continues) 22 of 29 | IBRAHIM ET AL.

TABLE 2 (Continued)

Compound Molecular Molecular No. name Source formula weight Reference

57 g-Aminobutyric acid- Fruit of H. polyrhizus, H. ocam- C13H17N2 O6 297 Wybraniec et al. (2007) betaxanthin ponis, H. undatus Fruit of H. polyrhizus Wybraniec et al. (2009)

58 Isoindicaxanthin Fruit of H. polyrhizus C14H17N2 O6 309 Wybraniec et al. (2009)

59 Portulacaxanthin II Fruit of H. polyrhizus C18H19N2 O7 375 Wybraniec et al. (2009) (tyrosine-bx)

60 Isoportulacaxanthin II Fruit of H. polyrhizus C18H19N2 O7 375 Wybraniec et al. (2009) (tyrosine-isobx)

61 Betanidin Fruits of Hylocereus sp. geno- C18H17N2 O8 389 Esquivel et al. (2007) types: Lisa, Nacional, Orejo- na, Rosa, and San Ignacio

62 Neobetanidin, bi- Juice of H. polyrhizus C16H13N 2O4 297 Herbach et al. (2005) decarboxylated, dehydrogenated

63 Miraxanthin V (dopa- Fruit of H. polyrhizus C17H19N2 O6 347 Wybraniec et al. (2009) mine-bx)

64 Isoleucine-Bx Fruit of H. polyrhizus C15H21N2 O6 325 Wybraniec et al. (2009)

65 Isoleucine-isoBx Fruit of H. polyrhizus C15H21N2 O6 325 Wybraniec et al. (2009)

66 Leucine-Bx (vulgax- Fruit of H. polyrhizus C15H21N2 O6 325 Wybraniec et al. (2009) anthin IV)

67 Leucine-isoBx (iso- Fruit of H. polyrhizus C15H21N2 O6 325 Wybraniec et al. (2009) vulgaxanthin IV)

68 Phenylalanine-Bx Fruit of H. polyrhizus C18H19N2 O6 359 Wybraniec et al. (2009)

69 Phenylalanine-isoBx Fruit of H. polyrhizus C18H19N2 O6 359 Wybraniec et al. (2009)

and variation (Lobo & Bender, 2008). It is commercially grown from $75,680/5-acre of an orchard. Total investing costs are evaluated northern Costa Rica to Nicaragua, where 3,000 tons are produced at $109,830 (without the land cost). The total values of operating annually on 420 ha. In 2006 in Florida, less than 50 acres were mature plant are evaluated to be $10,127/acre, with an average planted (Steele & Crane, 2006) and in 2010 the production has cost of $1.35/pound and a market yield of 19,000 pounds/acre. increased sixfold to be around 320 acres (Evans & Huntley, 2011). Total profit is determined to be $25,650/acre, leading to a net Its main season is summer (June to September). Twelve to eighteen profit $15,523/acre. That illustrates a very convenient profit in months is the time from planting until the beginning of harvesting. comparison with other tropical fruits, as avocados and mangoes Its yields range from 20 to 60 lb/plant (Gunasena, Pushpakumara, with a medium profit of $1,500/acre (Evans & Huntley, 2011). & Kariyawasam, 2006). Additionally, Hylocereus a perennial crop has a lifespan of 20–30 years, assuring that with appropriate concern, 7 | SAFETY AND TOXICITY STUDIES OF the crop can supply a stable income (Gunasena et al., 2006). The HYLOCEREUS SP crop also showed certain desirable agronomic features as the rela- tive ease of propagation. Thus, reduction of the expense usually The oral administered extract of H. polyrhizus fruit is relatively safe. connected with the buying of extra planting material, the simple Acute and subchronic toxicity studies of H. polyrhizus fruit showed that agronomic practices needed once the crop has been settled, and the administration of the MeOH extract of H. polyrhizus orally at doses the short turn around period of growing compared with other tropi- of 1,250, 2,500, and 5,000 mg/kg/day to female and male rats for 28 cal fruits. Furthermore, its cultivation would be lucrative over a 20- days did not show any mortality and adverse effects. Thus, its lethal year delineation horizon (Evans & Huntley, 2011). Moreover, it is a oral dose is more than 5,000 mg/kg and the NOAEL of the extract for drought-tolerant, so it is being grown in particular areas to replace both female and male rats is 5,000 mg/kg/day for 28 days (Hor et al., certain crops as avocados and citrus (Gunasena, Pushpakumara, 2012). H. polyrhizus pulp and peel extracts are considered nontoxic Kariyawasam, & Hardesty, 2015). A study performed by Evans and with NOAEL of more than 5 g/kg for pulp extracts and 3 g/kg for peel Huntley (2011) on an orchard of pitaya in South Florida revealed extracts, administered intra-peritoneal in mice. The NOAEL via oral that the cost of the establishment would be $15,136/acre, or administration for both pulp and peel extracts in mice were more than IBRAHIM ET AL. | 23 of 29

TABLE 3 List of phenolic compounds isolated from Hylocereus species

Molecular Molecular No. Compound name Source formula weight Reference

Flavonoids

70 Dihydroquercetin Flowers of H. undatus C15H12O7 304 Wu et al. (2011) 71 Dihydrokaempferol Flowers of H. undatus C15H12O6 288 Wu et al. (2011) 72 Kaempferol-3-O-b-D-glucopyranoside Flowers of H. undatus C21H20O11 448 Yi et al. (2012) 73 Kaempferol-3-neohespedridosoide Flowers of H. undatus C27H30O15 594 Wu et al. (2011) 74 Kaempferol-3-O-b-D-robinobioside Flowers of H. undatus C27H30O15 594 Yi et al. (2012) 75 Kaempferol-3-O-b-D-rutinoside Flowers of H. undatus C27H30O15 594 Yi et al. (2012) Fruit of H. polyrhizus Tenore et al. (2012)

76 Quercetin-3-O-b-D-rutinoside Flowers of H. undatus C27H30O16 610 Wu et al. (2011) Fruit of H. polyrhizus Tenore et al. (2012)

77 Isorhamnetin-3-O-b-D-robinobioside Flowers of H. undatus C28H32O16 624 Yi et al. (2012) 78 Kaempferol-3-O-b-D-glucopyranoside Flowers of H. undatus C22H22O12 478 Yi et al. (2012) Fruit of H. polyrhizus Tenore et al. (2012)

79 Isorhamnetin-3-O-b-D-rutinoside Flowers of H. undatus C28H32O16 624 Yi et al. (2012) Fruit of H. polyrhizus Tenore et al. (2012)

Phenolic acids and phenylpropanoids

80 P-Hydroxybenzoic acid Fruit of H. polyrhizus C7H6O3 138 Tenore et al. (2012) Seed oil of H. undatus, H. polyrhizus Lim et al. (2010)

81 Protocatechuic acid Fruit of H. polyrhizus C7H6O4 154 Tenore et al. (2012) Seed oil of H. undatus, H. polyrhizus Lim et al. (2010)

82 Vanillic acid Fruit of H. polyrhizus C8H8O4 168 Tenore et al. (2012) Seed oil of H. undatus, H. polyrhizus Lim et al. (2010)

83 Caffeic acid Fruit of H. polyrhizus C9H8O4 180 Tenore et al. (2012) Seed oil of H. undatus, H. polyrhizus Lim et al. (2010)

84 Gallic acid Fruit of H. polyrhizus C7H6O5 170 Tenore et al. (2012) Seed oil of H. undatus, H. polyrhizus Lim et al. (2010)

85 Syringic acid Fruit of H. polyrhizus C9H10O5 198 Tenore et al. (2012) Seed oil of H. undatus, H. polyrhizus Lim et al. (2010)

86 Trans-3,4-dimethoxycinnamic acid Flowers of H. undatus C11H12O4 208 Wu et al. (2011) 87 Trans-Ferulic acid Flowers of H. undatus C10H10O4 194 Wu et al. (2011) 88 P-Coumaric acid (88) Fruit of H. polyrhizus C9H8O3 164 Tenore et al. (2012) Seed oil of H. undatus, H. polyrhizus Lim et al. (2010)

89 Phthalic acid, 6-ethyloct-3-yl 2-ethylhexyl ester Peel fruits of H. polyrhizus, H. undatus C26H42O4 418 Luo et al. (2014) 90 1,2-Benzenedicarboxylic acid, mono Peel fruits of H. polyrhizus, H. undatus C16H22O4 278 Luo et al. (2014) (2-ethylhexyl) ester

91 Undatuside A Flowers of H. undatus C19H26O10 414 Wu et al. (2011) 92 Undatuside B Flowers of H. undatus C20H28O10 428 Wu et al. (2011) 93 Undatuside C Flowers of H. undatus C20H28O10 428 Wu et al. (2011) 94 Benzyl-b-D-glucopyranoside Flowers of H. undatus C13H18O6 270 Wu et al. (2011) 95 Phenylethyl-b-D-glucopyranoside Flowers of H. undatus C14H20O6 284 Wu et al. (2011)

TABLE 4 List of sterols, triterpenes, fatty acids, aliphatic, and miscellaneous compounds isolated from Hylocereus species

Molecular Molecular No. Compound name Source formula weight Reference

Sterols and triterpenes

96 Campesterol Peel fruits of H. polyrhizus, H. undatus C28H48O 400 Luo et al. (2014) Seed oil of H. undatus, H. polyrhizus Lim et al. (2010)

97 Stigmasterol Peel fruits of H. polyrhizus, H. undatus C29H48O 412 Luo et al. (2014) 98 g-Sitosterol Peel fruits of H. polyrhizus, H. undatus C29H50O 414 Luo et al. (2014) Seed oil of H. undatus, H. polyrhizus Lim et al. (2010)

99 b-Sitosterol Peel fruits of H. polyrhizus, H. undatus C29H50O 414 Luo et al. (2014) Seed oil of H. undatus, H. polyrhizus Lim et al. (2010)

100 Stigmast-4-en-3-one Peel fruits of H. polyrhizus, H. undatus C29H46O 410 Luo et al. (2014) 101 Ergosta-4,6,8(14), Peel fruits of H. polyrhizus, H. undatus C28H40O 392 Luo et al. (2014) 22-tetraen-3-one

102 Cholesterol Seed oil of H. undatus, H. polyrhizus C27H46O 386 Lim et al. (2010) 103 Taraxast-20-ene-3a-ol Leaves of H. undatus C30H50 O 426 Gutierrez et al. (2007) 104 Taraxast-12,20(30)- Leaves of H. undatus C30H48 O 424 Gutierrez et al. (2007) dien-3a-ol

105 a-Amyrin Peel fruits of H. polyrhizus, H. undatus C29H48O 412 Luo et al. (2014) 106 b-Amyrin Peel fruits of H. polyrhizus, H. undatus C29H48O 412 Luo et al. (2014) 107 Terpinolene Stem of H. polyrhizus C10H16 136 Ismail et al. (2017) (Continues) 24 of 29 | IBRAHIM ET AL.

TABLE 4 (Continued)

Molecular Molecular No. Compound name Source formula weight Reference

108 Eucalyptol Stem of H. polyrhizus C10H18O 154 Ismail et al. (2017) 109 b-Selinene Stem of H. polyrhizus C15H24 204 Ismail et al. (2017) 110 5-Cedranone Stem of H. polyrhizus C15H24O 220 Ismail et al. (2017)

Fatty acids and aliphatic compounds

111 Myristic acid Seed oil of H. undatus, H. polyrhizus C14H28O2 228 Ariffin et al. (2009); Liaotrakoon, Clercq, Hoed, and Dewettinc (2013); Lim et al. (2010)

112 Palmitic acid Peel fruits of H. polyrhizus,H. undatus C16H32 O2 256 Luo et al. (2014) Seed oil of H. undatus, H. polyrhizus Ariffin et al. (2009); Liaotrakoon et al. (2013); Lim et al. (2010) Seed oil of H. polyrhizus Villalobos-Gutierrez, Schweiggert, Carle, and Esquivel (2012)

113 Margaric acid Seed oil of H. undatus, H. polyrhizus C17H34O2 270 Liaotrakoon et al. (2013) 114 Stearic acid Seed oil of H. undatus, H. polyrhizus C18H36O2 284 Ariffin et al. (2009); Liaotrakoon et al. (2013); Lim et al. (2010) Seed oil of H. polyrhizus Villalobos-Gutierrez et al. (2012)

115 Arachidic acid Seed oil of H. undatus, H. polyrhizus C20H40O2 312 Liaotrakoon et al. (2013); Lim et al. (2010) Seed oil of H. polyrhizus Villalobos-Gutierrez et al. (2012)

116 Behenic acid Seed oil of H. undatus, H. polyrhizus C22H44O2 340 Liaotrakoon et al. (2013) 117 Lignoceric acid Seed oil of H. undatus, H. polyrhizus C24H48O2 368 Liaotrakoon et al. (2013) 118 Oleic acid Peel fruits of H. polyrhizus, H. undatus C18H34O2 282 Luo et al. (2014) Seed oil of H. undatus, H. polyrhizus Ariffin et al. (2009); Liaotrakoon et al. (2013); Lim et al. (2010) Seed oil of H. polyrhizus Villalobos-Gutierrez et al. (2012)

119 Palmitoleic acid Seed oil of H. undatus, H. polyrhizus C16H30O2 254 Ariffin et al. (2009); Liaotrakoon et al. (2013); Lim et al. (2010) Seed oil of H. polyrhizus Villalobos-Gutierrez et al. (2012)

120 Cis-Vaccenic acid Seed oil of H. undatus, H. polyrhizus C18H34O2 282 Ariffin et al. (2009) Seed oil of H. polyrhizus Villalobos-Gutierrez et al. (2012)

121 Erucic acid Seed oil of H. undatus, H. polyrhizus C22H42O2 338 Liaotrakoon et al. (2013); Lim et al. (2010)

122 Gadoleic acid Seed oil of H. undatus, H. polyrhizus C20H38O2 310 Liaotrakoon et al. (2013) 123 Hexadecadienoic acid Seed oil of H. undatus, H. polyrhizus C16H28O2 252 Liaotrakoon et al. (2013) 124 Linoleic acid Peel fruits of H. polyrhizus, H. undatus C18H32 O2 280 Luo et al. (2014) Seed oil of H. undatus, H. polyrhizus Ariffin et al. (2009); Liaotrakoon et al. (2013); Lim et al. (2010) Seed oil of H. polyrhizus Villalobos-Gutierrez et al. (2012)

125 2-Chloroethyl linoleate Peel fruits of H. polyrhizus, H. undatus C20H35ClO2 342 Luo et al. (2014) 126 Linolenic acid Seed oil of H. undatus, H. polyrhizus C18H30O2 278 Ariffin et al. (2009); Liaotrakoon et al. (2013); Lim et al. (2010)

127 Eicosatrienoic acid Seed oil of H. undatus, H. polyrhizus C20H34O2 306 Liaotrakoon et al. (2013) 128 Arachidonic acid Seed oil of H. undatus, H. polyrhizus C20H32O2 304 Liaotrakoon et al. (2013) 129 1-Nonadecene Peel fruits of H. polyrhizus, H. undatus C19H38 266 Luo et al. (2014) 130 17-Pentatriacontene Peel fruits of H. polyrhizus, H. undatus C35H70 490 Luo et al. (2014) 131 Octacosane Peel fruits of H. polyrhizus, H. undatus C28H58 394 Luo et al. (2014) 132 Eicosane Peel fruits of H. polyrhizus, H. undatus C20H42 282 Luo et al. (2014) 133 Tetratriacontane Peel fruits of H. polyrhizus, H. undatus C34H70 478 Luo et al. (2014) 134 1-Tetracosanol Peel fruits of H. polyrhizus, H. undatus C24H50O 354 Luo et al. (2014) 135 Heptacosane Peel fruits of H. polyrhizus, H. undatus C27H56 380 Luo et al. (2014) 136 11-Hexacosyne Peel fruits of H. polyrhizus, H. undatus C26H50 362 Luo et al. (2014) 137 Octadecanal Peel fruits of H. polyrhizus, H. undatus C18H36O 268 Luo et al. (2014) 138 Nonacosane Peel fruits of H. polyrhizus, H. undatus C29H60 408 Luo et al. (2014) 139 Octadecane Peel fruits of H. polyrhizus, H. undatus C18H38 354 Luo et al. (2014) 140 Docosane Peel fruits of H. polyrhizus, H. undatus C22H46 310 Luo et al. (2014)

Miscellaneous compounds

141 (R)-(2) Citramalic Flowers of H. undatus C6H10O4 146 Wu et al. (2011) acid

142 (R)-(2) Citramalic Flowers of H. undatus C7H12O4 160 Wu et al. (2011) acid-1-methyl ester

143 (R)-(2) Citramalic Flowers of H. undatus C7H12O4 160 Wu et al. (2011) acid-4-methyl ester

144 a-Tocopherol Seed oil of H. undatus, H. polyrhizus C29H50O2 430 Liaotrakoon et al. (2013); Lim et al. (2010)

145 b-Tocopherol Seed oil of H. undatus, H. polyrhizus C28H48O2 416 Lim et al. (2010) (Continues) IBRAHIM ET AL. | 25 of 29

TABLE 4 (Continued)

Molecular Molecular No. Compound name Source formula weight Reference

146 g-Tocopherol Seed oil of H. undatus, H. polyrhizus C28H48O2 416 Liaotrakoon et al. (2013); Lim et al. (2010)

147 d-Tocopherol Seed oil of H. undatus, H. polyrhizus C27H46O2 402 Liaotrakoon et al. (2013); Lim et al. (2010)

148 Squalene Peel fruits of H. polyrhizus, H. undatus C30H50 410 Luo et al. (2014) 149 Trichloroacetic acid, Peel fruits of H. polyrhizus, H. undatus C18H33Cl3O2 386 Luo et al. (2014) hexadecyl ester

150 Hexadecyl oxirane Peel fruits of H. polyrhizus, H. undatus C18H36O 268 Luo et al. (2014) 151 6-Tetradecanesulfonic Peel fruits of H. polyrhizus, H. undatus C18H38 O3S 344 Luo et al. (2014) acid, butyl ester

5 g/kg. Moreover, H. polyrhizus pulp and peel extracts were nontoxic in 8 | CONCLUSION WRL68 and HepG2 in vitro. The peel extract caused cell death in

HepG2 cells with a high IC50 (4.2 mg/mL), which is considered nontoxic Currently, the awareness of consumer for healthy food products is according to the NCI. Intake of exaggerated amounts of H. polyrhizus growing and food researchers have been looking for beneficial sources fruit resulted in pseudo-hematuria which is a harmless reddish discolor- of healthy components. Antioxidants from a natural source are more ation of the feces and urine (Shakir, 2009). idealistic as food due to their free radical scavenging effects.

FIGURE 16 Chemical structures of fatty acids and aliphatic compounds (111–140) isolated form Hylocereus species 26 of 29 | IBRAHIM ET AL.

FIGURE 17 Chemical structures of other compounds (141–151) isolated form Hylocereus species

Additionally, they are safer and healthier than synthetic ones. Pitaya adsorption onto TiO2 for dye-sensitized solar cell applications. Spec- fruit is one of the most known fruits that is commercially grown in dif- trochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 138, 130–137. ferent countries of the world for its nutritional advantages. It has Amid, M., Manap, Y., & Zohdi, N. K. (2014). Microencapsulation of acquired a wide acceptance for its pharmacological actions against a purified amylase enzyme from pitaya (Hylocereus polyrhizus)peel variety of ailments. Recently, many studies have shown it to exhibit dif- in Arabic gum-chitosan using freeze drying. Molecules, 19(3), ferent bioactivities, some of which justified its uses in various cultures. 3731–3743. The present review focused on the pharmacological activities and nutri- Arevalo-Galarza, M. L., & Ortiz-Hernandez, Y. D. (2004). Comporta- tional benefits of pitaya fruit. It contains bioactive phytoconstituents miento poscosecha del fruto de la pitahaya (Hylocereus undatus). Cactaceas y Suculentas Mexicanas XLIX Ano~ , 49,85–90. which might participate directly or indirectly to the highlighted biologi- Ariffin, A. A., Bakar, J., Tan, C. P., Rahman, R. A., Karim, R., & Loi, C. C. cal effects in this review. These compounds can be taken into account (2009). Essential fatty acids of pitaya (dragon fruit) seed oil. Food as favorable candidates for the evolution of effective and novel phar- Chemistry, 114(2), 561–564. maceutical leads. Deep phytochemical studies of pitaya fruit and its Celis, C. Q., Gil, D. E., & Pino, J. A. (2012). Characterization of odor- pharmacological effects, especially the way of action of its constituents active compounds in yellow pitaya (Hylocereus megalanthus (Haw.) – to clarify the relation between traditional uses and pharmacological Britton et Rose). Revista CENIC Ciencias Químicas, 43,1 6. activities will obviously be the focus of further research. Charoensiri, R., Kongkachuichai, R., Suknicom, S., & Sungpuag, P. (2009). Beta-carotene, lycopene, and alpha-tocopherol contents of selected Thai fruits. Food Chemistry, 113(1), 202–207. CONFLICT OF INTEREST Chemah, T. C., Aminah, A., Noriham, A., & WanAida, W. M. (2010). We wish to confirm that there are no known conflicts of interest Determination of pitaya seeds as a natural antioxidant and source of essential fatty acids. International Food Research Journal, 17, associated with this publication and there has been no significant 1003–1010. financial support for this work that could have influenced its Choo, W. S., & Yong, W. K. (2011). Antioxidant properties of two species outcome. of Hylocereus fruits. Advances in Applied Science Research, 2, 418–425. Chung, H. H., Schwinn, K. E., Ngo, H. M., Lewis, D. H., Massey, B., Calcott, K. E., ... Harrison, D. K. (2015). Characterisation of beta- ORCID lain biosynthesis in Parakeelya flowers identifies the key biosyn- Sabrin Ragab Mohamed Ibrahim http://orcid.org/0000-0002-6858- thetic gene DOD as belonging to an expanded LigB gene family 7560 that is conserved in betalain-producing species. Frontiers in Plant Science, 6, 499. Cisneros, A., & Tel-Zur, N. (2012). Evaluation of interspecific-interploid REFERENCES hybrids (F1) and Back Crosses (BG1) in Hylocereus species (Cacta- Al-Alwani, M. A. M., Mohamad, A., Kadhum, A. A. H., & Ludin, N. A. ceae). In Swan, A. (Ed.), Meiosis: Molecular mechanisms and cytogenetic (2015). Effect of solvents on the extraction of natural pigments and diversity (pp. 367–388). Rijeka, Croatia: InTech Publishers. IBRAHIM ET AL. | 27 of 29

Eka, Y. P., Hendarto, H. & Widjiati (2017). Effect of Hylocereus polyrhizus Herbach, K. M., Stintzing, F. C., & Carle, R. (2004). Thermal degradation rind extract toward interleukin-1b, vascular endothelial growth factor of betacyanins in juices from purple pitaya [Hylocereus polyrhizus expression, endometriosis implant area. International Journal of Phar- (Weber) Britton & Rose] monitored by high-performance liquid maceutical and Clinical Research, 9, 617–621. chromatography-tandem mass spectrometric analyses. European Food – Elfi Susanti, V. H., Utomo, S. B., Syukri, Y., & Redjeki, T. (2012). Research and Technology, 219, 377 385. Phytochemical screening and analysis polyphenolic antioxidant activ- Herbach, K. M., Stintzing, F. C., & Carle, R. (2005). Identification of heat- ity of methanolic extract of white dragon fruit (Hylocereus undatus). induced degradation products from purified betanin, phyllocactin and Indonesian Journal of Pharmacy, 23,60–64. hylocerenin by high-performance liquid chromatography/electrospray Esatbeyoglu, T., Wagner, A. E., Motafakkerazad, R., Nakajima, Y., ionization mass spectrometry. Rapid Communications in Mass Spec- – Matsugo, S., & Rimbach, G. (2014). Free radical scavenging and anti- trometry, 19(18), 2603 2616. oxidant activity of betanin: Electron spin resonance spectroscopy Hollman, P. C. H., Hertog, M. G. L., & Katan, M. B. (1996). Analysis and studies and studies in cultured cells. Food and Chemical Toxicology, health effects of flavonoids. Food Chemistry, 57,43–46. 73, 119–126. Hor, S. Y., Ahmad, M., Farsi, E., Yam, M. F., Hashim, M. A., Lim, C. P., ... Escobar, B. A., Gomez, G. Y., Bautista, R. E., & Perez, G. R. S. (2010). Asmawi, M. Z. (2012). Safety assessment of methanol extract of red Evaluacion de la actividad antimicrobiana de cactaceas mexicanas dragon fruit (Hylocereus polyrhizus): Acute and subchronic toxicity Hylocereus sp. y Opuntia ficus. In: Memorias del VII. Encuentro Nacional studies. Regulatory Toxicology and Pharmacology, 63(1), 106–114. de Biotecnología del Instituto Politecnico Nacional. Mazatlan, Mexico: ICBF. (1992). Tabla de composicion de alimentos. ICBF. Sexta edicion, Memorias. 12 pp. INCAP y FAO (Cited in El Cultivo de Pitaya y su Posicionamiento en Esquivel, P., Stintzing, F. C., & Carle, R. (2007). Phenolic compound el Mercado. Retrieved from http://www.angelfire.com/ia2/ingenier- profiles and their corresponding antioxidant capacity of purple pitaya iaagricola/pitaya.htm (Hylocereus sp.) genotypes. Zeitschrift fur€ Naturforschung, 62c, Islam, A. T., Chowdhury, M. A. U., Uddin, M. E., Rahman, M. M., Habib, 636–644. M. R., Uddin, M. G. M., & Rahman, M. A. (2013). Protective effect of Evans, E. A., & Huntley, J. (2011). Economics of establishing and produc- methanolic extract of Hylocereus polyrhizus fruits on carbon ing pitaya in Southern Florida: A stochastic budget analysis. HortTech- tetrachloride-induced hepatotoxicity in rat. European Journal of Medic- nology, 21, 246–251. inal Plants, 3, 500–507. FAMA. (2006). Dragon fruit (Hylocereus undatus). Retrieved from http:// Ismail, O. M., Abdel-Aziz, M. S., Ghareeb, M. A., & Hassan, R. Y. A. eshoppe.famaxchange.org/index.php?ac5147&ch5ctlg_fspd&pg5ctlg_ (2017). Exploring the biological activities of the Hylocereus polyrhizus fspd_fruit&tpt5eshoppe extract. Journal of Innovations in Pharmaceutical and Biological Scien- ces, 4,01–06. Gandía-Herrero, F., Escribano, J., & García-Carmona, F. (2007). Characterization of the activity of tyrosinase on betanidin. Journal of Jaafar, R. A., Abdul Rahman, A. R., Mahmod, N. Z. C., & Vasudevan, R. Agricultural and Food Chemistry, 55(4), 1546–1551. (2009). Proximate analysis of dragon fruit (Hylecereus polyhizus). American Journal of Applied Sciences, 6, 1341–1346. Gandía-Herrero, F., Escribano, J., & Garcìa-Carmona, F. (2016). Biological activities of plant pigments betalains. Critical Reviews in Food Science Kalt, W. (2005). Effects of production and processing factor on major and Nutrition, 56(6), 937–945. fruit and vegetable antioxidants. Journal of Food Science, 70,11–19. Gandía-Herrero, F., & Gandía-Carmona, F. (2013). Biosynthesis of beta- Khalili, M. A. R., Norhayati, A. H., Rokiah, M. Y., Asmah, R., Siti Muskinah, lains: Yellow and violet plant pigments. Trends in Plant Science, 18(6), M., & Abdul Manaf, A. (2009). Hypocholesterolemic effect of red pit- 334–343. aya (Hylocereus sp.) on hypercholesterolemia induced rats. Interna- tional Food Research Journal, 16, 431–440. Gunasena, H. P. M., Pushpakumara, D. K. N. G., & Kariyawasam, M. (2006). Dragon fruit-Hylocerus undatus (Haw.) Britton and rose: Field Khan, M. I. (2016). Plant betalains: Safety, antioxidant activity, clinical manual for extension workers. Sri Lanka Council for agricultural Pol- efficacy, and bioavailability. Comprehensive Reviews in Food Science icy, Wijerama Mawatha, Colombo 7, Sri Lanka. and Food Safety, 15(2), 316–330. Gunasena, H. P. M., Pushpakumara, D. K. N. G., Kariyawasam, M., & Le Bellec, F. L., Vaillant, F., & Imbert, E. (2006). Pitahaya (Hylocereus spp.): Hardesty, S. (2015). Pitahaya or dragon fruit - A new, water efficient A new fruit crop, a market with a future. Fruits, 61(4), 237–250. crop for Southern California farmers. Agriculture and Natural Resour- Liaotrakoon, W., Clercq, N., Hoed, V. V., & Dewettinc, K. (2013). Dragon ces, University of California fruit (Hylocereus spp.) seed oils: Their characterization and stability Gutierrez, R. M. P., Solís, R. V., Baez, E. G., & Flores, J. M. M. (2007). under storage conditions. Journal of the American Oil Chemists’ Soci- Microvascular protective activity in rabbits of triterpenes from Hylo- ety, 90(2), 207–215. cereus undatus. Journal of Natural Medicines, 61(3), 296–301. Lim, H. K., Tan, C. P., Karim, R., Ariffin, A., & Bakar, J. (2010). Chemical Halimoon, N., & Abdul Hasan, M. H. (2010). Determination and evalua- composition and DSC thermal properties of two species of Hylocer- tion of antioxidative activity in red dragon fruit (Hylocereus undatus) eus cacti seed oil: Hylocereus undatus and Hylocereus polyrhizus. Food and green kiwi fruit (Actinidia deliciosa). American Journal of Applied Chemistry, 119(4), 1326–1331. Sciences, 7, 1432–1431 438. Lim, T. K. (2012). Edible medicinal and non-medicinal plants. In: Fruits Harris, N. N., Javellana, J., Davies, K. M., Lewis, D. H., Jameson, P. E., (Vol. 1, pp. 640–655). Dordrecht, the Netherlands: Springer Science, Deroles, S. C., ... Schwinn, K. E. (2012). Betalain production is possi- Business Media B. V. ble in anthocyanin-producing plant species given the presence of Lobo, R., & Bender, G. (2008). Pitahaya field test yields preliminary DOPA-dioxygenase and L-DOPA. BMC Plant Biology, 12(1), 34. results. In Small farm news, small farm program (Vol. 2). Davis, CA: Hatlestad, G. J., Sunnadeniya, R. M., Akhavan, N. A., Gonzalez, A., University of California at Davis. Goldman, I. L., McGrath, J. M., & Lloyd, A. M. (2012). The beet R Lugo-Radillo, A., Delgado-Enciso, I., & Pena-Beltran, E. (2012). Betanidin locus encodes a new cytochrome P450 required for red betalain pro- significantly reduces blood glucose levels in BALB/c mice fed with an duction. Nature Genetics, 44(7), 816–820. atherogenic diet. Natural Products and Bioprospecting, 2(4), 154–155. 28 of 29 | IBRAHIM ET AL.

Luo, H., Cai, Y., Peng, Z., Liu, T., & Yang, S. (2014). Chemical composition Stintzing, F. C., Conrad, J., Klaiber, I., Beifuss, U., & Carle, R. (2004). and in vitro valuation of the cytotoxic and antioxidant activities of Structural investigations on betacyanin pigments by LC NMR and 2D supercritical carbon dioxide extracts of pitaya (dragon fruit) peel. NMR spectroscopy. Phytochemistry, 65(4), 415–422. – Chemistry Central Journal, 8(1), 1 7. Stintzing, F. C., Schieber, A., & Carle, R. (2002). Betacyanins in fruits Montoya-Arroyo, A., Schweiggert, R. M., Pineda-Castro, M., Sramek, M., from red-purple pitaya, Hylocereus polyrhizus (Weber) Britton & Rose. Kohlus, R., Carle, R., & Esquivel, P. (2014). Characterization of cell Food Chemistry, 77(1), 101–106. wall polysaccharides of purple pitaya (Hylocereus sp.) pericarp. Food Sudha, K., Baskaran, D., Ramasamy, D., & Siddharth, M. (2017). Evaluation of – Hydrocolloids, 35, 557 564. functional properties of Hylocereus undatus (White dragon fruit). Interna- Nagai, T., Reiji, I., Hachiro, I., & Nobutaka, S. (2003). Preparation and tional Journal of Agricultural Science and Research, 7,451–456. antioxidant properties of water extract of propolis. Food Chemistry, Sunnadeniya, R., Bean, A., Brown, M., Akhavan, N., Hatlestad, G., Gonzalez, – 80(1), 29 33. A., ... Riechers, D. E. (2016). Tyrosine hydroxylation in betalain pig- Nerd, A., & Mizrahi, Y. (1998). Fruit development and ripening in yellow ment biosynthesis is performed by cytochrome P450 enzymes in beets pitaya. Journal of the American Society for Horticultural Science, 123, (Beta vulgaris). PLoS One, 11(2), e0149417. – 560 562. Taira, J., Tsuchida, E., Katoh, M. C., Uehara, M., & Ogi, T. (2015). Antioxi- Nurmahani, M. M., Osman, A., Abdul Hamid, A., Mohamad, G., & Pak, D. F. dant capacity of betacyanins as radical scavengers for peroxyl radical (2012). Antibacterial property of Hylocereus polyrhizus and Hylocereus and nitric oxide. Food Chemistry, 166, 531–536. – undatus peel extracts. International Food Research Journal, 19,77 84. Tenore, G. C., Novellino, E., & Basile, A. (2012). Nutraceutical potential Obenland, D., Cantwell, M., Lobo, R., Collin, S., Sievert, J., & Arpaia, M. L. and antioxidant benefits of red pitaya (Hylocereus polyrhizus) extracts. (2016). Impact of storage conditions and variety on quality attributes Journal of Functional Foods, 4(1), 129–136. and aroma volatiles of pitahaya (Hylocereus spp.). Scientia Horticul- Thammarutwasik, P., Hongpattarakere, T., Chantachum, S., Kijroongrojana, – turae, 199,15 22. K., Itharat, A., Reanmongkol, W., ... Ooraikul, B. (2009). Prebiotics - A Okonogi, S., Duangrat, C., Anuchpreeda, S., Tachakittirungrod, S., & review. SJST, 31,401–408. Chowwanapoonpohn, S. (2007). Comparison of antioxi dant capacities Toivonen, P. M. A., & Brummell, D. A. (2008). Biochemical bases of – and cytotoxicities of certain fruit peels. Food Chemistry, 103(3), 839 846. appearance and texture changes in fresh-cut fruit and vegetables. Omidizadeh, A. (2009). Effects of antioxidant and dietary fiber content of Postharvest Biology and Technology, 48(1), 1–14. fresh and oven-dried red pitaya fruit (Hylocereus polyrhizus.) on hyper- Tze, N. L., Han, C. P., Yusof, Y. A., Ling, C. N., Talib, R. A., Taip, F. S., & cholesterolemic and insulin-resistant rats (Master thesis). University Aziz, M. G. (2012). Physicochemical and nutritional properties of Putra Malaysia, Malaysia. spray-dried pitaya fruit powder as natural colorant. Food Science and Omidizadeh, A., Yusof, R. M., Roohinejad, S., Ismail, A., Abu Bakar, M. Z., Biotechnology, 21(3), 675–682. & Bekhit, A. E. A. (2014). Anti-diabetic activity of red pitaya (Hylocer- Villalobos-Gutierrez, M. G., Schweiggert, R. M., Carle, R., & Esquivel, P. – eus polyrhizus) fruit. RSC Advances, 4(108), 62978 62986. (2012). Chemical characterization of Central American pitaya (Hylo- Perez, R. M. G., Vargas, R. S., & Ortiz, Y. D. H. (2005). Wound healing cereus sp.) seeds and seed oil. CyTA – Journal of Food, 10(1), 78–83. properties of Hylocereus undatus on diabetic rats. Phytotherapy Wichienchot, S., Jatupornpipat, M., & Rastall, R. A. (2010). Oligosaccha- – Research, 19, 665 668. rides of pitaya (dragon fruit) flesh and their prebiotic properties. Food Ramli, N. S., Brown, L., Ismail, P., & Rahmat, A. (2014). Effects of red pit- Chemistry, 120(3), 850–857. aya juice supplementation on cardiovascular and hepatic changes in Widyaningsih, A., Setiyani, O., Umaroh, U., Sofro, M. A. U., & Amri, F. high-carbohydrate, high-fat diet-induced metabolic syndrome rats. (2017). Effect of consuming red dragon fruit (Hylocereus costaricensis) – BMC Complementary and Alternative Medicine, 14(1), 1 10. juice on the levels of hemoglobin and erythrocyte among pregnant Royal Botanic Garden Kew. (2016). Retrieved from http://www.theplant- women. Belitung Nursing Journal, 3, 255–264. list.org/tpl1.1/search?q5Hylocereus1 Wu, L., Hsu, H., Chen, Y., Chiu, C., Lin, Y., & Ho, J. A. (2006). Antioxidant Sakihama, Y., Maeda, M., Hashimoto, M., Tahara, S., & Hashidoko, Y. and antiproliferative activities of red pitaya. Food Chemistry, 95(2), (2012). Beetroot betalain inhibits peroxynitrite-mediated tyrosine 319–327. – nitration and DNA strand cleavage. Free Radical Research, 46,93 99. Wu, X., Wang, Y., Huang, X., Fan, C., Wang, G., Zhang, X., ... Ye, W. Sakuta, M. (2014). Diversity in plant red pigments: Anthocyanins and (2011). Three new glycosides from Hylocereus undatus. Journal of betacyanins. Plant Biotechnology Reports, 8(1), 37–48. Asian Natural Products Research, 13(8), 728–733. Schliemann, W., Kobayashi, N., & Strack, D. (1999). The decisive step in Wybraniec, S., & Mizrahi, Y. (2004). Influence of perfluorinated carbox- betaxanthin biosynthesis is a spontaneous reaction. Plant Physiology, ylic acids on ion-pair reversed-phase high-performance liquid chro- 119(4), 1217–1232. matographic separation of betacyanins and 17-decarboxy- – – Shakir, S. M. M. (2009). Antioxidant capacity, safety and effects of Hylocer- betacyanins. Journal of Chromatography A, 1029(1 2), 97 101. eus polyrhizus (red dragon fruit) in STZ-diabetic rats (Master thesis). Wybraniec, S., Nowak-Wydra, B., Mitka, K., Kowalski, P., & Mizrahi, Y. Universiti Teknologi MARA, Malaysia. (2007). Minor betalains in fruits of Hylocereus species. Phytochemistry, – Siddiq, M., & Nasir, M. (2012). Dragon fruit and durian. In M. Siddiq 68(2), 251 259. (Ed.), Tropical and subtropical fruits: Postharvest physiology, processing Wybraniec, S., Nowak-Wydra, B., & Mizrahi, Y. (2006). 1H and 13C NMR and packaging (1st ed., pp 587–596). Oxford, UK: Wiley. spectroscopic structural elucidation of new decarboxylated betacya- – Steele, D., & Crane, J. H. (2006). The state of the Florida tropical fruit nins. Tetrahedron Letters, 47(11), 1725 1728. industry and the challenges growers face. Proceedings of the Florida Wybraniec, S., Platzner, I., Geresh, S., Gottlieb, H. E., Haimberg, M., State Horticultural Society, 119,7–8. Mogilnitzki, M., & Mizrahi, Y. (2001). Betacyanins from vine cactus – Stintzing, F. C., & Carle, R. (2004). Functional properties of anthocyanins Hylocereus polyrhizus. Phytochemistry, 58(8), 1209 1212. and betalains in plants, food and in human nutrition. Trends in Food Wybraniec, S., Stalica, P., Jerz, G., Klose, B., Gebers, N., Winterhalter, P., Science and Technology, 15(1), 19–38. ... Mizrahi, Y. (2009). Separation of polar betalain pigments from cacti IBRAHIM ET AL. | 29 of 29

fruits of Hylocereus polyrhizus by ion-pair high-speed countercurrent antioxidant activity in yogurt. International Journal of Biological Scien- chromatography. Journal of Chromatography A, 1216(41), 6890–6899. ces, 8,93–98. Yi, Y., Zhang, Q., Li, S., Wang, Y., Ye, W., Zhao, J., & Wang, Y. (2012). Zakharova, N. S., & Petrova, T. A. (2000). b-Glucosidases from leaves Simultaneous quantification of major flavonoids in “Bawanghua”, the and roots of the common beet, Beta vulgaris. Applied Biochemistry edible flower of Hylocereus undatus using pressurised liquid extrac- and Microbiology, 36(4), 394–397. tion and high performance liquid chromatography. Food Chemistry, Zohdi, N. K., & Amid, M. (2013). Optimization of extraction of novel pec- 135(2), 528–533. tinase enzyme discovered in red pitaya (Hylocereus polyrhizus) Peel. Zaidel, D. N. A., Rashid, J. M., Hamidon, N. H., Salleh, L. M., & Kassim, A. Molecules, 18(11), 14366–14380. S. M. (2017). Extraction and characterisation of pectin from dragon fruit (Hylocereus polyrhizus) peels. Chemical Engineering Transactions, – 56, 805 810. How to cite this article: Ibrahim SRM, Mohamed GA, Khedr Zainoldin, K. H., & Baba, A. S. (2009). The effect of Hylocereus polyrhizus AIM, Zayed MF, El-Kholy AA-ES. Genus Hylocereus:Beneficial and Hylocereus undatus on physicochemical, proteolysis, and antioxi- phytochemicals, nutritional importance, and biological relevance dant activity in yogurt. World Academy of Science, Engineering and —Areview.JFoodBiochem. 2018;e12491. https://doi.org/ Technology, 3,12–27. 10.1111/jfbc.12491 Zainoldin, K. H., & Baba, A. S. (2012). The effect of Hylocereus polyrhizus and Hylocereus undatus on physicohemical, proteolysis, and