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  • Dragon Fruit (Hylocerus species) as a Potential CNS Modulator: Emerging Evidence from Neuroprotective, Antioxidant and Behavioural Studies

  • Department of Pharmacology, RBVRR Women’s College of Pharmacy (Affiliated to Osmania University), Telangana, India, 500027

Abstract

Hylocereus, commonly known as dragon fruit or pitaya, is a tropical cactus fruit with significant nutritional and bioactivity potential. This review summarizes diverse studies exploring the health-promoting properties and industrial applications of dragon fruit pulp and peel.[1]Both fruit parts are rich in antioxidants, vitamins, minerals, and phytochemicals, such as betalains, flavonoids, polyphenols, and alkaloids, contributing to their anti-diabetic, anti-inflammatory, neuroprotective, anticancer, and antimicrobial effects[2]. Experimental models, including rodents, zebrafish, nematodes, and in vitro assays, have demonstrated the efficacy of the fruit in reducing oxidative stress, improving cognitive function, alleviating anxiety, and protecting against heavy metal toxicity, thereby causing neuromodulation[3]. Dragon fruit contains magnesium and antioxidants that may help regulate neurotransmitters, promoting better sleep quality and reducing mood- and age-related disorders[4]. Collectively, these findings highlight the potential of dragon fruit as a promising sustainable resource for health applications and functional food development.

Keywords

Hylocereus, Phytochemicals, betalains, Antioxidants, Oxidative stress, Neuromodulation.

Introduction

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Hylocereus is a fruit plant that is indigenous to tropical and subtropical regions of America. It produces fruits known as dragon fruit and pitaya. Pitaya dragon fruit is a rustic fruit belonging to the Cactaceae family and the genus Hylocereus[4]. It is known as dragon fruit because of its bright red skin with overlapping green fins covering the fruit[5]. As dragon fruit flowers usually bloom at night, this led to the birth of terms such as “mistress of the night” and “moon flower,” which indirectly explains why dragon fruit is also called the “belle of the night” or “night-blooming cereus.” The health-promoting potential of pitaya fruit is due to the presence of bioactive compounds that confer numerous benefits, such as anti-diabetic, anti-inflammatory, antioxidant, anti-cancer, and antimicrobial properties. As a result of these beneficial actions, the consumption of this fruit has increased in different regions worldwide. Dragon fruit pulp, rind, seeds, flower buds, and dried flowers contain high levels of antioxidants, fiber, vitamin C, and minerals[6].Dragon fruit is rich in bioactive phytochemicals, including betalains, flavonoids, polyphenols, terpenoids, steroids, saponins, alkaloids, and tannins [7]. Numerous studies have examined the antioxidant capacity of dragon fruit and discovered that it has a high antioxidant capacity.The natural pigments found in dragon fruit peels are typically thrown away as food waste and have not been utilised to their full potential. This is regrettable because the dragon fruit itself has a number of benefits. This crop's greatest benefit is that, once planted, it will grow for roughly 20 years, and one hectare may support about 800 dragon fruit plants. Israel, Vietnam, Taiwan, Nicaragua, Australia, and the US are among the countries where it is grown commercially.[19]

Dragon fruit belongs to the Cactaceae family and is cultivated widely in tropical and subtropical regions. Species including Hylocereus undatus (white-fleshed dragon fruit) and Hylocereus polyrhizus (red-fleshed dragon fruit) are rich sources of natural pigments and bioactive compounds[5]. Although commonly consumed as a functional food, increasing evidence indicates that dragon fruit may influence neurological health through antioxidant, anti-inflammatory and neurotransmitter-modulating mechanisms.[3,5,6]

The CNS is highly vulnerable to oxidative damage due to its high oxygen requirement and lipid-rich neuronal membranes.[9]Excessive oxidative stress contributes to anxiety, depression, cognitive decline and neurodegenerative disorders[10]. Natural antioxidants from fruits have therefore attracted attention as potential neuroprotective agents[11].

PHYTOCHEMICAL BASIS OF CNS MODULATION

Dragon fruit contains betalains, flavonoids, phenolic acids, polyphenols, terpenoids, alkaloids and squalene. These compounds may reduce reactive oxygen species, inhibit inflammatory mediators and preserve neuronal integrity. Magnesium and antioxidant components may also contribute to neurotransmitter regulation and sleep-related benefits.

Current Evidence of Dragon Fruit as CNS Modulator from in vivo Studies:

Sr. No

Source/ Model

Treatment/ Methodology

Parameters Evaluated

Major Findings

1

H. undatus pulp and peel extract; rodent models

Regular administration for the assessment of anxiolytics and antidepressant

Tail suspension test, raised plus maze, forced swim test, and neurotransmitter analysis

Produced anxiolytic and antidepressant-like effects by modifying the GABA and serotonin pathways.[12]

2

H. polyrhizus and H. undatus extracts

Aqueous, ethanolic, and methanolic extract

Assays for tyrosinase inhibition, FRAP, and DPPH

Revealed a significant level of antioxidant activity; red dragon fruit had a great antioxidant capacity.[13]

3

H. undatus pulp extract; animal behavioural model

21 days of oral administration

Increased levels of acetylcholine, glutathione, SOD, catalase, MDA, and plus maze

Enhanced cholinergic activity and antioxidant protection.[14]

4

H. undatus extract; zebrafish copper toxicity model

Treatment for copper exposure that is both preventive and curative

Cholinergic function, oxidative stress indicators, locomotion, and survival assay

Decreased neurotoxic stress, elevated cortisol, and anxiety-like behaviour.[15]

5

H. undatus fruit peel extract; C. elegans model

Peel extract treatment for both transgenic and wild-type strains

Gene expression, fluorescence microscopy, neuronal survival, and lifespan

Demonstrated anti-aging and neuroprotective properties via DAF-16-mediated mechanisms.[16]

6

Red pitaya (Hylocereus undatus) extract; C. elegans stress model

Administration of fruit extract both prior to and following stress induction

Antioxidant enzymes, the cholinergic system, and behavioural reaction

Prevented and reversed the damage that stress causes to the antioxidant and cholinergic systems [17]

7

H. undatus pulp and peel volatile constituents

Evaluation of squalene-rich extract

Assays for the inhibition of acetylcholinesterase, COX-2, and 5-lipoxygenase

Enzyme modulation may have anti-inflammatory and anti-Alzheimer properties [5]

8

H. polyrhizus peel extract; endurance model

Various oral dosage

Antioxidant assessment and natatory exhaustion test

Decreased oxidative tiredness and increased physical stamina.[7]

9

H. polyrhizus pulp and peel; zebrafish model

Exposure to immersion and behavioural evaluation

Chemical profiling and light-dark behavioural testing

Showed anxiolytic-like effects and may have involved the GABAergic pathway.[18]

10

Dragon fruit phytochemical studies

Evaluation of bioactive compounds

Assays for phenolics, flavonoids, betalains, and antioxidants

Confirmed that by lowering oxidative damage, phytochemicals may help protect the central nervous system.[20]

CONCLUSION:

Dragon fruit is a multipurpose fruit with significant health advantages and industrial potential. Bioactive substances with potent antioxidant, neuroprotective, anti-inflammatory, and antibacterial qualities are abundant in its pulp and peel.[21] The fruit's capacity to promote cognitive health, lower anxiety, and guard against oxidative and neurotoxic assaults has been demonstrated by these bioactivities, which have been verified in a number of animals. Crucially, the peel—which is frequently disposed of as waste—acts as a useful natural source of pigment. Dragon fruit is a sustainable and affordable resource for functional foods, nutraceuticals, and natural feed additives due to its long productive lifespan and adaptation to various growing environments [22, 23]. Utilising pulp and peel to their fullest capacity can cut waste and significantly increase the crop's value in commercial and health-related industries.[9]

REFERENCES

  1. Bishoyi AK, Saeed F, Shehzadi U, Shankar A, Balaji J, Kaur J, Afzaal M, Imran A, Rasheed M, Hussain B, Hussain M. Nutritional composition, phytochemical profile, and health benefits of Hylocereus Undatus (pitaya): A comprehensive review. eFood. 2024 Oct;5(5):e70017.
  2. Coelho VS, de Moura DG, Aguiar LL, Ribeiro LV, Silva VD, da Veiga Correia VT, Melo AC, Silva MR, de Paula AC, de Araújo RL, Melo JO. The Profile of phenolic compounds identified in pitaya fruits, health effects, and food applications: An integrative review. Plants. 2024 Oct 28;13(21):3020.
  3. Jiang H, Zhang W, Li X, Shu C, Jiang W, Cao J. Nutrition, phytochemical profile, bioactivities and applications in food industry of pitaya (Hylocereus spp.) peels: A comprehensive review. Trends in Food Science & Technology. 2021 Oct 1;116:199-217.
  4. Safira A, Savitri SL, Putri AR, Hamonangan JM, Safinda B, Solikhah TI, Khairullah AR, Puspitarani GA. Review on the pharmacological and health aspects of Hylocereus or Pitaya: An update. Journal of Drug Delivery and Therapeutics. 2021 Nov 1;11(6):297-303.
  5. Eldeen IS, Foong S, Ismail N, Wong K. Regulation of pro-inflammatory enzymes by the dragon fruits from Hylocereus undatus (Haworth) and squalene-its major volatile constituents. Pharmacognosy Magazine. 2020;16(68):81-6.
  6. Wu LC, Hsu HW, Chen YC, Chiu CC, Lin YI, Ho JA. Antioxidant and antiproliferative activities of red pitaya. Food chemistry. 2006 Mar 1;95(2):319-27.
  7. Lira SM, Dionísio AP, Holanda MO, Marques CG, da Silva GS, Correa LC, Santos GB, de Abreu FA, Magalhães FE, de Lima Rebouças E, Guedes JA. Metabolic profile of pitaya (Hylocereus polyrhizus (FAC Weber) Britton & Rose) by UPLC-QTOF-MSE and assessment of its toxicity and anxiolytic-like effect in adult zebrafish. Food Research International. 2020 Jan 1;127:108701.
  8. Uttara B, Singh AV, Zamboni P, Mahajan R. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Current neuropharmacology. 2009 Mar 1;7 (1):65-74.
  9. Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. International journal of biomedical science: IJBS. 2008 Jun;4(2):89.
  10. Nishikito DF, Borges AC, Laurindo LF, Otoboni AM, Direito R, Goulart RD, Nicolau CC, Fiorini AM, Sinatora RV, Barbalho SM. Anti-inflammatory, antioxidant, and other health effects of dragon fruit and potential delivery systems for its bioactive compounds. Pharmaceutics. 2023 Jan 3;15(1): 159.
  11. Walvekar SS, Naikwade NS, Patil SS, Mulla AK, Khot PN. Evaluation of antidepressant and anxiolytic activity of fruit extract of Hylocereus undatus in experimental animals. International Journal of Pharmaceutical Sciences and Drug Research. 2022;14(5):509-518. doi: 10.25004/IPSDR.2022.140502.
  12. Tenore GC, Novellino E, Basile A.Nutraceutical potential and antioxidant activity of red and white pitaya (Hylocereus species) fruits.Journal of Functional Foods. 2012;4(2):375–382.
  13. Shahed S, Hussaini F, Ali MA, Ahmed SM, Naseer A, et al. Screening of Anti-Alzheimer’s Activity against Scopolamine-Induced Amnesia in Mice Model. Int J Pharm Sci Rev Res. 2022;76(1):96-103. doi:10.47583/ijpsrr.2022.v76i01.018.
  14. Tamagno WA, Santini W, Alves C, Vanin AP, Pompermaier A, Bilibio D, Sutorillo NT, Kaizer RR, Barcellos LJ. Neuroprotective and antioxidant effects of pitaya fruit on Cu-induced stress in adult zebrafish. Journal of food biochemistry. 2022 Jul; 46(7):14147.
  15. Prasanth MI, Prasansuklab A, Verma K, Brimson JM, Malar DS, Tencomnao T.Hylocereus undatus extends lifespan and exerts neuroprotection in Caenorhabditis elegans via DAF-16 mediated pathway. Nutrition and Healthy Aging. 2023 May 26;8 (1):79-95.
  16. Tamagno WA, Vanin AP, Sutorillo NT, Bilibio D, Dada RA, Colla LM, Zamberlan DC, Kaizer RR, Barcellos LJ. Fruit extract of red pitaya (Hylocereus undatus) prevents and reverses stress-induced impairments in the cholinergic and antioxidant systems of Caenorhabditis elegans. Journal of food biochemistry. 2022Apr; 46(4):e13981.
  17. Wahdah N, Praristiya MR, Mahdi N. Test of the tonic effects of dragon fruit extract (cortice hylocereus polyrhizus) on white miice. Journal of Pharmacology Experiment and Pharmaceutical Technology. 2025 Mar 11;1(1):33-8.
  18. Prasanth MI, Prasansuklab A, Verma K, Brimson JM, Malar DS, Tencomnao T.Hylocereus undatus extends lifespan and exerts neuroprotection in Caenorhabditis    elegans via DAF-16 mediated pathway. Nutrition and Healthy Aging. 2023 May 26;8 (1):79-95.
  19. Chen SY, Xu CY, Mazhar MS, Naiker M. Nutritional Value and Therapeutic Benefits of Dragon Fruit: A Comprehensive Review with Implications for Establishing Australian Industry Standards. Molecules. 2024 Nov 30;29(23):5676. doi:
  20. Nishikito DF, Borges AC, Laurindo LF, Otoboni AM, Direito R, Goulart RD, Nicolau CC, Fiorini AM, Sinatora RV, Barbalho SM. Anti-inflammatory, antioxidant, and other health effects of dragon fruit and potential delivery systems for its bioactive compounds. Pharmaceutics. 2023 Jan 3;15(1): 159.
  21. Le Bellec F, Vaillant F, Imbert E. Pitahaya (Hylocereus spp.): a new fruit crop, a market with a future. Fruits. 2006 Jul; 61(4):237-50.
  22. Azeredo HM. Betalains: properties, sources, applications, and stability:a review. International Journal of Food Science and Technology. 2009 Dec;44(12):2365-76

Reference

  1. Bishoyi AK, Saeed F, Shehzadi U, Shankar A, Balaji J, Kaur J, Afzaal M, Imran A, Rasheed M, Hussain B, Hussain M. Nutritional composition, phytochemical profile, and health benefits of Hylocereus Undatus (pitaya): A comprehensive review. eFood. 2024 Oct;5(5):e70017.
  2. Coelho VS, de Moura DG, Aguiar LL, Ribeiro LV, Silva VD, da Veiga Correia VT, Melo AC, Silva MR, de Paula AC, de Araújo RL, Melo JO. The Profile of phenolic compounds identified in pitaya fruits, health effects, and food applications: An integrative review. Plants. 2024 Oct 28;13(21):3020.
  3. Jiang H, Zhang W, Li X, Shu C, Jiang W, Cao J. Nutrition, phytochemical profile, bioactivities and applications in food industry of pitaya (Hylocereus spp.) peels: A comprehensive review. Trends in Food Science & Technology. 2021 Oct 1;116:199-217.
  4. Safira A, Savitri SL, Putri AR, Hamonangan JM, Safinda B, Solikhah TI, Khairullah AR, Puspitarani GA. Review on the pharmacological and health aspects of Hylocereus or Pitaya: An update. Journal of Drug Delivery and Therapeutics. 2021 Nov 1;11(6):297-303.
  5. Eldeen IS, Foong S, Ismail N, Wong K. Regulation of pro-inflammatory enzymes by the dragon fruits from Hylocereus undatus (Haworth) and squalene-its major volatile constituents. Pharmacognosy Magazine. 2020;16(68):81-6.
  6. Wu LC, Hsu HW, Chen YC, Chiu CC, Lin YI, Ho JA. Antioxidant and antiproliferative activities of red pitaya. Food chemistry. 2006 Mar 1;95(2):319-27.
  7. Lira SM, Dionísio AP, Holanda MO, Marques CG, da Silva GS, Correa LC, Santos GB, de Abreu FA, Magalhães FE, de Lima Rebouças E, Guedes JA. Metabolic profile of pitaya (Hylocereus polyrhizus (FAC Weber) Britton & Rose) by UPLC-QTOF-MSE and assessment of its toxicity and anxiolytic-like effect in adult zebrafish. Food Research International. 2020 Jan 1;127:108701.
  8. Uttara B, Singh AV, Zamboni P, Mahajan R. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Current neuropharmacology. 2009 Mar 1;7 (1):65-74.
  9. Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. International journal of biomedical science: IJBS. 2008 Jun;4(2):89.
  10. Nishikito DF, Borges AC, Laurindo LF, Otoboni AM, Direito R, Goulart RD, Nicolau CC, Fiorini AM, Sinatora RV, Barbalho SM. Anti-inflammatory, antioxidant, and other health effects of dragon fruit and potential delivery systems for its bioactive compounds. Pharmaceutics. 2023 Jan 3;15(1): 159.
  11. Walvekar SS, Naikwade NS, Patil SS, Mulla AK, Khot PN. Evaluation of antidepressant and anxiolytic activity of fruit extract of Hylocereus undatus in experimental animals. International Journal of Pharmaceutical Sciences and Drug Research. 2022;14(5):509-518. doi: 10.25004/IPSDR.2022.140502.
  12. Tenore GC, Novellino E, Basile A.Nutraceutical potential and antioxidant activity of red and white pitaya (Hylocereus species) fruits.Journal of Functional Foods. 2012;4(2):375–382.
  13. Shahed S, Hussaini F, Ali MA, Ahmed SM, Naseer A, et al. Screening of Anti-Alzheimer’s Activity against Scopolamine-Induced Amnesia in Mice Model. Int J Pharm Sci Rev Res. 2022;76(1):96-103. doi:10.47583/ijpsrr.2022.v76i01.018.
  14. Tamagno WA, Santini W, Alves C, Vanin AP, Pompermaier A, Bilibio D, Sutorillo NT, Kaizer RR, Barcellos LJ. Neuroprotective and antioxidant effects of pitaya fruit on Cu-induced stress in adult zebrafish. Journal of food biochemistry. 2022 Jul; 46(7):14147.
  15. Prasanth MI, Prasansuklab A, Verma K, Brimson JM, Malar DS, Tencomnao T.Hylocereus undatus extends lifespan and exerts neuroprotection in Caenorhabditis elegans via DAF-16 mediated pathway. Nutrition and Healthy Aging. 2023 May 26;8 (1):79-95.
  16. Tamagno WA, Vanin AP, Sutorillo NT, Bilibio D, Dada RA, Colla LM, Zamberlan DC, Kaizer RR, Barcellos LJ. Fruit extract of red pitaya (Hylocereus undatus) prevents and reverses stress-induced impairments in the cholinergic and antioxidant systems of Caenorhabditis elegans. Journal of food biochemistry. 2022Apr; 46(4):e13981.
  17. Wahdah N, Praristiya MR, Mahdi N. Test of the tonic effects of dragon fruit extract (cortice hylocereus polyrhizus) on white miice. Journal of Pharmacology Experiment and Pharmaceutical Technology. 2025 Mar 11;1(1):33-8.
  18. Prasanth MI, Prasansuklab A, Verma K, Brimson JM, Malar DS, Tencomnao T.Hylocereus undatus extends lifespan and exerts neuroprotection in Caenorhabditis    elegans via DAF-16 mediated pathway. Nutrition and Healthy Aging. 2023 May 26;8 (1):79-95.
  19. Chen SY, Xu CY, Mazhar MS, Naiker M. Nutritional Value and Therapeutic Benefits of Dragon Fruit: A Comprehensive Review with Implications for Establishing Australian Industry Standards. Molecules. 2024 Nov 30;29(23):5676. doi:
  20. Nishikito DF, Borges AC, Laurindo LF, Otoboni AM, Direito R, Goulart RD, Nicolau CC, Fiorini AM, Sinatora RV, Barbalho SM. Anti-inflammatory, antioxidant, and other health effects of dragon fruit and potential delivery systems for its bioactive compounds. Pharmaceutics. 2023 Jan 3;15(1): 159.
  21. Le Bellec F, Vaillant F, Imbert E. Pitahaya (Hylocereus spp.): a new fruit crop, a market with a future. Fruits. 2006 Jul; 61(4):237-50.
  22. Azeredo HM. Betalains: properties, sources, applications, and stability:a review. International Journal of Food Science and Technology. 2009 Dec;44(12):2365-76

Photo
Soha Sultana
Corresponding author

Department of Pharmacology, RBVRR Women’s College of Pharmacy (Affiliated to Osmania University), Telangana, India, 500027

Photo
Jorige Archana
Co-author

Department of Pharmacology, RBVRR Women’s College of Pharmacy (Affiliated to Osmania University), Telangana, India, 500027

Photo
Namitha Ponnala
Co-author

Department of Pharmacology, RBVRR Women’s College of Pharmacy (Affiliated to Osmania University), Telangana, India, 500027

Soha Sultana, Jorige Archana, Namitha Ponnala, Dragon Fruit (Hylocerus species) as a Potential CNS Modulator: Emerging Evidence from Neuroprotective, Antioxidant and Behavioural Studies, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 7, 1841-1845. https://doi.org/10.5281/zenodo.21267720

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