Healthy Benefits of Hylocereus Species: Comparison
Please note this is a comparison between Version 2 by Jessie Wu and Version 1 by LUCAS FORNARI LAURINDO.
The dragon fruit of pitaya is a rustic fruit belonging to the Cactaceae family, the genus Hylocereus. It is known as dragon fruit due to the presence of bright red skin with overlapping green fins covering the fruit. Other common names given to this fruit are pitahaya, dragon pearl fruit, night-blooming cereus, strawberry pear, and Cinderella plant. Depending on the species, its fruits may have different characteristics, such as shape, presence of thorns, skin, and pulp color, reflecting high genetic variability. The health-promoting potential of pitaya fruit is due to the presence of bioactive compounds related to numerous benefits such as anti-diabetic, anti-inflammatory, antioxidant, anti-cancer, and antimicrobial. As a result of these beneficial actions, the consumption of this fruit has increased in different regions worldwide.
  • dragon fruit
  • pitaya
  • antioxidant
  • anti-inflammatory
  • health effects
  • delivery system

1. Introduction

Dragon fruit has been used as a medicinal food since ancient times by Mayas—using the fruit and the flowers as a hypoglycemic, wound disinfectant and diuretic, for dysentery, tumor dissolution, and as a healing agent. Moreover, the flowers and the seeds can be used as beverages for gastritis, as laxatives, and to improve kidney function. These properties are derived from the multi-bioactive compounds found in this plant, mainly in the fruit. Furthermore, it shows no toxicity since a study with dragon fruit extract at a dose of 1250 to 5000 mg/kg did not produce interferences or abnormalities in the organs of animal models [65,66,67,68][1][2][3][4]. Below it is possible to find some effects of pitaya fruit.
As the results found in Table 1 show, the use of pitaya pulp or its bioactive compounds can exert anxiolytic, antioxidant, and anti-inflammatory effects in animal models. Improvements in hepatic steatosis and reduction of liver injury are also observed, in addition to balancing the intestinal microbiota. These results in animal studies allow us to say they can also be observed in humans.
Table 1.
In vivo biological and pharmacological activities of various pitaya extracts and pure compounds.
Properties Plant Part or Active Compounds Species Extraction Experimental Model Dose Route of Administration Methods of Analysis Observations References
Anxiolytic-like effects
Hylocereus species. ↑—increase; ↓—decrease; HDL-c—high-density lipoprotein cholesterol; LDL-c—low-density lipoprotein cholesterol.
Based on the inclusion and exclusion criteria for the search of studies that were performed using pitaya in humans, only five clinical trials were added to Table 4. The risk of bias observed in these studies is found in Table 5. These trials are commented on below.
ALT—Alanine transaminase; AMP—adenosine monophosphate; AMPK—AMP-activated protein kinase; AST—aspartate aminotransferase; AT—adipose tissue; CYP2E1—cytochrome P450 2E1; FGF-21—fibroblast growth factor 21; Ikb-a—Ikb kinase alpha; Insr—insulin receptor gene; IL-1β—interleukin 1 beta; IR—insulin resistance; MyD88—myeloid differentiation primary response gene 88; NF-kb—nuclear factor kappa b; Nrf2—nuclear factor erythroid 2-related factor 2; PPAR-α—peroxisome proliferator-activated receptor; Pomc—proopiomelanocortin gene; SREBP-1—hepatic sterol regulatory element-binding protein 1c; TLR4—toll-like receptor 4; TNF-α—tumor factor necrosis alfa.

2. Antioxidant Effects by Species

Hylocereus. polyrhizus is rich in betalains and other bioactive compounds such as vitamins and phenolic compounds that exert relevant antioxidant properties and, for these reasons, are related to the prevention of several human diseases. The oil results from the seeds, and the peel is also an essential source of antioxidant compounds. The peel of H. undatus possesses more flavonoids than the flesh [65,66,67,69][1][2][3][17] (Table 2).
Table 2.
Main bioactive compounds of pulp, peel, and seeds of the genus
Hylocereus
.
References Bioactive Compounds Pulp, Peel, or Seed Molecular Structures Health Effects Concentration

(Dry Weight)
[45,46][18][
[
6
]
[
20
]
Phthalic acid
Peel Pharmaceutics 15 00159 i011 Antioxidant (NA)
[39][36] Benzoic acids derivatives: salicylic acid (a),

3- hydroxyl benzoic acid (b),

4-hydroxy benzoic acid (c).
Peel and Pulp Pharmaceutics 15 00159 i012 Antioxidant Variando de 0.48 ± 0.0 a 11.97 ± 0.8 µg/100 g (pulp and peel)
[6,49,60][20][23][37] Caffeic acid Peel and seed Pharmaceutics 15 00159 i013 Antioxidant 0.08 mg/100 g (pulp and peel)
[45,61][18][38] Quercetin Peel and pulp Pharmaceutics 15 00159 i014 Antioxidant, anti-inflammatory, anti-diabetic 3.43 mg/100 g (pulp)

Peel (NA)
[44,48,62,63,64][22][39][40][41][42] Fatty acids:

oleic acid (a),

linoleic acid (b), linolenic acid (c), and palmitic acid (d)
Pulp and seeds Pharmaceutics 15 00159 i015 Nutraceutical activity 129.11 (a), 252.65 (b), 5.33 (c), 62.74 (d)

mg/100 g (pulp) and 60 (a), 21 (c), 13 (d) g/100 g (seeds)
The antioxidant properties of dragon fruit extract were investigated. Total antioxidant status was reduced in pre-diabetic and normocholesterolemic subjects that consumed red pitaya [16,18][43][44]. Harahap and Amelia [70][45] showed that fruit extract could minimize oxidative damage production in animals submitted to physical exercises. Other authors have shown that the pulp extract can decrease oxidative damage in STZ-induced diabetes in rats [71][46].
Putri et al. [72][47] showed that the intake of red dragon fruit could reduce malondialdehyde levels in diabetic rats and, for these reasons, is associated with reducing the oxidative stress related to this disease. Figure 1 shows the main antioxidant effects associated with the Hylocereus species.
Figure 1.
Main antioxidant effects of
Hylocereus
species and their health effects. ↑—increase; ↓— decrease.

3. Anti-Inflammatory Effects

Besides the antioxidant actions, dragon fruit can also exert anti-inflammatory actions. Saenjum et al. [45][18] found anthocyanins (cyanidin 3-glucoside, delphinidin 3-glucoside, and pelargonidin 3-glucoside) in the pulp and peel of pitaya red. The authors found that the pulp enriched with the first anthocyanin (cyanidin 3-glucoside) inhibited the synthesis of reactive oxygen and nitrogen species, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), in in vitro models and without resulting in cytotoxicity.
Another study showed that the dragon flesh and peel extract and the isolated squalene led to the inhibition of pro-inflammatory enzymes such as cyclooxygenase-2 lipoxygenase and acetylcholinesterase and concluded that this fruit could produce a significant potential for the control and management of inflammatory processes through different pathways that may include, prostaglandin, leukotriene, and cholinergic pathways [73][48].
Amim et al. [74][49] found different effects (anti-inflammatory, antioxidant and anti-bacterial actions) in the extracts of H. polyrhizus and H. undatus (the aqueous extract of H. polyrhizus showed most significant effects than H. undatus). The authors found that the aqueous extract of these species resulted in more protective anti-inflammatory and antioxidant activities compared to the ethyl acetate and ethanolic extracts.
Al-Radadi et al. [75][50] found significant anti-inflammatory, anti-diabetic, anti-Alzheimer, and cytotoxic effects of gold nanoparticles using H. polyrhizus.
Figure 2 shows the most prominent anti-inflammatory effects associated with the Hylocereus species.
Figure 2.
Main anti-inflammatory effects of
Hylocereus
species and their health effects. ↓—decrease.

4. Prebiotic Effects

The main carbohydrates in white and red flesh dragon fruit are glucose, fructose, and oligosaccharides. The mixed oligosaccharides are resistant to hydrolysis by human α-amylase and artificial human gastric juice (about 34.88% and 4.04%, respectively). Moreover, the mixed oligosaccharides can also stimulate the growth of lactobacilli and bifidobacterial, thus showing prebiotic properties [76][51].
Dasaesamoh et al. [77][52] showed that the fecal fermentation of pitaya oligosaccharides increased the populations of Bifidobacteria and Lactobacillus and reduced the populations of Bacteroides and Clostridium. Moreover, this fecal fermentation resulted in a positive prebiotic effect. Lactic acid, acetic acid, propionic, and butyric acids were produced at substantial concentrations.

5. Antimicrobial Effects

In a study to investigate the antimicrobial effect of red pitaya peels, Temak et al. [78][53] found that the extract has efficient in vivo and in vitro effects against several microorganisms, such as Escherichi coli and P. aeruginosa.
Sushmitha et al. [79][54] investigated the effects of H. undatus seeds in Gram-negative and Gram-positive bacterial species and found that the minimum inhibitory concentration is 50 µL for Staphylococcus aureus and Escherichia coli. Tenore et al. [80][55] also found antimicrobial activity for hexane, chloroform, and ethanol extract of the skin of H. undatus and showed inhibition of the growth of Gram-negative and Gram-positive bacteria.
Extract of the peel and fruit of the red dragon fruit can also exert anti-fungal actions against Rhizoctonia solani, Candida albicans, Aspergillus flavus, Botrytis cinerea, Fusarium oxysporum, and Cladosporium herbarum [80][55].

6. Anti-Cancer Effects

Some studies have shown the anti-cancer potential of dragon fruit. Divakaran et al. [81][56] aimed to evaluate the ability of this fruit to produce nanoparticles and found they can significantly inhibit the growth of MCF-7 breast cancer cells.
Another study showed that the fecal fermentation of pitaya oligosaccharides augmented the populations of Lactobacillus and decreased the populations of Bacteroides and Clostridium, and resulted in the production of lactic acid, acetic acid, propionic and butyric acids that can inhibit Caco-2 cells and has a potential for risk reduction in colon cancer [77][52].
In a very interesting study, Padmavathy et al. [37][57] demonstrated that methanol extracts of H. undatus have promising anti-cancer effects against human liver cancer (HepG-2) cells.
Wu et al. [82][58] investigated the anti-proliferative effect of red pitaya on B16F10 melanoma cells. They showed that the peel has stronger inhibition of the growth of these cancer cells than the flesh. The authors concluded that both peel and flesh are rich in polyphenols and good sources of antioxidants, and for these reasons, the peel can inhibit the growth of melanoma cells.
The anti-cancer activities promoted by pitaya are related to several bioactive compounds such as phenolic acids, flavonoids, and betacyanin [83,84][59][60].
Figure 3
shows the most pronounced anti-cancer effects associated with the
Hylocereus
species.
Figure 3.
Main anti-cancer effects of
Hylocereus
species. ↑—increase; ↓—decrease.

7. Anti-Diabetic Effects

Many studies have demonstrated that the consumption of red pitaya can reduce glycemia in humans [16,17,18][43][44][61]. In a systematic revisewarch and meta-analysis, Poolsup et al. [8][62] found that dragon fruit can be used to prevent diabetes.
The study of Putri et al. [72][47] showed that pitaya associated with metformin could significantly decrease glycemia and HOMA-IR (homeostasis model assessment-Insulin Resistance) in type 2 diabetic rats. The authors suggested that red dragon fruit could be used as an alternative to metformin due to its effectiveness in decreasing HOMA-IR (and thus, insulin resistance) and malondialdehyde levels. Moreover, the consumption of red pitaya promoted a hypoglycemic effect in dyslipidemic C57BL/6 mice, contributing to reducing the risk of insulin resistance [85][63].
Fadlilah and Sucipto [19][64] found that pitaya (H. polyrhizus) effectively reduces fasting blood sugar levels in students who consume high calories daily.
Marietta et al. [86][65] investigated the effects of red pitaya skin extract on glycemia and lipid profile of diabetic and dyslipidemic male Wistar rats and found no significant reduction in glycemia.

8. Anti-Lipidemic Effects

The use of red pitaya can improve lipid profile, decrease total cholesterol, LDL-c, and triglycerides, and increase HDL-c levels in normocholesterolemic subjects, pre-diabetic, and type 2 diabetic patients [16,17,18][43][44][61].
The consumption of red pitaya also showed benefits in lipid levels in dyslipidemic C57BL/6 mice, contributing to reducing cardiovascular diseases [85][63].
The study of Marietta et al. [86][65] evaluated the effects of the consumption of red pitaya skin extract on the lipid profile of male Wistar rats with diabetes and dyslipidemia and did not find a significant reduction in the lipid profile of these animals.
Setiawan et al. [87][66] investigated the effects of H. polyrhizus peel powder on male Balb-c mice. Their results showed decreased triglycerides, total cholesterol levels, and LDL-c. Moreover, they observed an increase in HDL-c levels. The authors concluded that the use of the peel of this fruit could improve the blood lipid of mice with hyperlipidemia.
Figure 4 shows the most relevant anti-lipidemic and anti-diabetic effects associated with the Hylocereus species and how these effects are associated with atherosclerosis. Table 3 summarizes some in vitro studies performed with pitaya.
Figure 4. Cardiovascular protective effects of the

9. The Effects of Dragon Fruit on Humans: Evaluation of Clinical Trials

Shafie et al. [18][44] investigated the effects of using spray pitaya powder (SPP) in normocholesterolemic subjects. All the doses led to reductions in total cholesterol and LDL-c (p < 0.05); however, the higher the dose, the higher the reduction in cholesterol levels. For the blood levels of triglycerides and HDL-c, there were significant differences (decrease and increase, respectively) in the higher dose (p < 0.05).
In the study of Akhiruddin [16][43], the pre-diabetic participants were allocated to receive pitaya powder (obtained from H. polyrhizus) in different concentrations. At the end of the treatment, compared to the control group, the group that received 100 g per day showed the best reduction in blood glucose (22.90%, p < 0.05). The same was observed for the lipid levels; there was a significant reduction (p < 0.05) in total cholesterol (26.44%), triglycerides (20.54%), and LDL-c (69.55%) (the higher the dose, the higher the percentage of reduction). Moreover, the group that received 100 g of the red pitaya powder presented an increase of 63.8% in HDL-c levels. Although the results of these two studies are very interesting, the authors did not mention the participants’ age and gender.
Abd Hadi et al. [17][61] investigated the effects of consuming pitaya fruit in type 2 diabetic subjects that receive red pitaya daily. Participants were subjected to a seven-week trial consisting of phase 1 (one week) and phase 2 (4 weeks) of treatment, and phase 3 (2 weeks of wash-out). The results showed a reduction (p < 0.05) in glycemia and lipids.
Fadlilah and Sucipto [19][64] investigated the effects of red pitaya intake on students’ blood pressure and glycemia after excessive food consumption. The obtention of the samples was performed using consecutive sampling techniques with thirty-two respondents each for the treatment and control groups. The glycemia pre-test and post-test in the treated group were 87.5 mg/dL and 81.0 mg/dL, respectively, and in the control group were 83.00 mg/d and 82.0 mg/dL, respectively. The systolic blood pressure pre- and post-test were 112 mmHg and 115 mmHg, respectively, in the control group, compared to 117 mmHg and 109 mmHg, in the intervention group. The diastolic blood pressure pre-test and post-test were 79 mmHg and 82 mmHg in the control group; in the treated group, it was 77 mmHg and 70 mmHg in the pre- and post-test, respectively.
The study performed by Cheok et al. [20][76] showed that pitaya intake significantly improved acute low-mediated dilation (p < 0.001) compared to placebo. Pulse wave velocity was significantly decreased (p = 0.003), whereas the augmentation index improved after fourteen days (p = 0.02). Although the results of this trial are interesting, it is biased due to the small sample and a short-time follow-up that could interfere with the interpretation of the results.
Since the pulp and the skin of Hylocereus can exert antioxidant and anti-inflammatory actions, the consumption of this plant, as shown by the trials mentioned above, can reduce the risk of several diseases related to oxidative stress and inflammatory processes. These diseases include diabetes, dyslipidemia, metabolic syndrome, and cardiovascular conditions.

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