skip to main content

Red dragon fruit juice in reducing ros levels and insulin resistance In rats with type 2 diabetes mellitus model

1Masters Program in Clinical Nutrition and Nutrition Sciences, Universitas Sebelas Maret, Indonesia

2Department of Nutrition, Faculty of Medicine, Universitas Sebelas Maret, Indonesia

3Department of Public Health, Faculty of Medicine, Universitas Sebelas Maret, Indonesia

Received: 8 Oct 2020; Published: 22 Dec 2021.

Citation Format:

Background: The peel of red dragon fruit (Hylocereus polyrhizus) had been proven to have a total polyphenol content and total flavonoids 2 to 3 times more than its flesh. These components could reduce oxidative stress and maintain the function of pancreatic beta cells, which could affect blood sugar levels.

Objectives: This study aimed to test the red dragon fruit juice using peel and flesh to reduce oxidative stress and insulin resistance in T2DM model rats.

Materials and Methods: This study was a true experimental study with a randomized controlled trial, with a Matching Pretest Post-test Control Group Design. We used 21 white male rats (Rattus norvegicus) Wistar strain which was divided into three groups: (P1) negative control group (induced Streptozotocin + Nicotinamide induction), (P2) positive control group (given Streptozotocin + Nicotinamide and given Metformin HCl induction 0,9 mg/kg BW, and (P3) Red Dragon fruit group (induced Streptozotocin + Nicotinamide and given Red Dragon Fruit juice 3.6 ml / 200 g BW / day given for 14 days. The data were analyzed using a one-way ANOVA test, paired t-test, and Post Hoc.

Results: After 14 days of intervention, the average HOMA-IR levels were as follows: negative control group (Mean=8.32; SD=0.26), positive group (Mean 4.89; SD=0.29), and the Red Dragon Fruit intervention group (Mean=4.65; SD=0.30). The average MDA levels were as follows: control group (Mean = 9.08; SD = 0.68), positive group (Mean=3.34;SD=0.22), and the red dragon fruit intervention group (Mean = 3.05; SD = 0.47). Both the Metformin group and the Red Dragon Fruit group had low HOMA-IR and MDA levels compared to the negative control group.

Conclusions: When administered alone, red dragon fruit and metformin effectively reduced HOMA-IR and MDA levels in rats with type 2 DM. Red dragon fruit can be used as an alternative to metformin because of its effectiveness in reducing plasma HOMA-IR and MDA.

Fulltext View|Download
Keywords: HOMA-IR; Red Dragon Fruit; Type 2 Diabetes Mellitus

Article Metrics:

  1. Ee SC, Bakar J, Kharidah M, Dzulkifly MH, Noranizan A. Physico-chemical properties of spray-dried red pitaya (Hylocereus polyrhizus) peel powder during storage. Int Food Res J. 2014. 21(3):1177–82
  2. Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. Vol. 5. Cambridge University Press: Journal of Nutritional Science; 2016. 5:e47
  3. Ramli NS, Ismail P, Rahmat A. Influence of Conventional and Ultrasonic-Assisted Extraction on Phenolic Contents, Betacyanin Contents, and Antioxidant Capacity of Red Dragon Fruit ( Hylocereus polyrhizus ). Vol 20114. Sci World J; 2014. 4:1–7
  4. Kim H, Choi H-K, Moon JY, Kim YS, Mosaddik A, Cho SK. Comparative Antioxidant and Antiproliferative Activities of Red and White Pitayas and Their Correlation with Flavonoid and Polyphenol Content. J Food Sci: 2011. 76(1): C38–45
  5. Hurtado MD, Vella A. What is type 2 diabetes?. United Kingdom: Medicine; 2019. 47(1):10–5
  6. Bajaj S, Khan A. Antioxidants and diabetes. Indian J Endocrinol Metab; 2012.16(Suppl 2): S267
  7. Jheng H-F, Tsai P-J, Guo S-M, Kuo L-H, Chang C-S, Su I-J, et al. Mitochondrial fission contributes to mitochondrial dysfunction and insulin resistance in skeletal muscle. Mol Cell Biol: 2012. 32(2):309–19
  8. Tiwari AK, Rao JM. Diabetes mellitus and multiple therapeutic approaches of phytochemicals: Present status and prospects [Internet]. Vol. 83. Current Science; 2002. 30–8
  9. Widowati W. Potensi Antioksidan sebagai Antidiabetes. Jurnal Kesehatan Masyarakat; 2008. 7(2):1–11
  10. Gaweł S, Wardas M, Niedworok E, Wardas P. Malondialdehyde (MDA) as a lipid peroxidation marker. Vol. 57. Poland: Wiadomości lekarskie; 2004. 453–5
  11. CDC. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States. Atlanta: GA: Centers for Disease Control and Prevention; 2017 (downloaded: 25 12 2019). Available from:
  12. Tang Q, Li X, Song P, Xu L. Optimal cut-off values for the homeostasis model assessment of insulin resistance (HOMA-IR) and pre-diabetes screening: Developments in research and prospects for the future. Vol. 9. Drug discoveries & therapeutics; 2015. 380–5
  13. Vinayagam R, Xu B. Antidiabetic properties of dietary flavonoids: A cellular mechanism; review. Vol. 12. London: Nutrition and Metabolism; 2015. 12-60
  14. Graf BA, Milbury PE, Blumberg JB. Flavonols, flavones, flavanones, and human health: Epidemiological evidence. Vol. 8, Journal of Medicinal Food. 2005. p. 281–90
  15. Clemens R, Drewnowski A, Ferruzzi MG, Toner CD, Welland D. Squeezing fact from fiction about 100% fruit juice. Adv Nutr; 2015. 6(2):236S-243S
  16. Murphy MM, Barrett EC, Bresnahan KA, Barraj LM. 100 % Fruit juice and measures of glucose control and insulin sensitivity: a systematic review and meta-analysis of randomized controlled trials. J Nutr Sci; 2017. 6:e59
  17. Rejeki MSW, Wirawanni Y. Pengaruh Pemberian Jus Mentimun Dan Tomat Terhadap Kadar Glukosa Darah Postprandial Perempuan Overweight Dan Obesitas. J Nutr Coll; 2015. 4(2):220–5
  18. Barbara G. Wells, Joseph T. DiPiro, Terry L. Schwinghammer, Cecily V. DiPiro. Pharmacotherapy Handbook, Seventh Edition. 2009 (downloaded: 7 Oct 2020]. Available from:
  19. Parasuraman S, Zhen KM, Raveendran R. Retro-orbital Blood Sample Collection in Rats-a Video Article. Pharmacol Toxicol Biomed Reports; 2015.1(2):37–40
  20. Nurhidajah N, Nurrahman N. Efek Hipoglikemik Kecambah Beras Merah pada Tikus yang Diinduksi STZ-NA dengan Parameter Kadar Insulin, Indeks HOMA-IR dan HOMA β. Jurnal Online Universitas Gadjah Mada; 2016. 36(4):433–9
  21. Szkudelski T. Streptozotocin–nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Exp Biol Med; 2012. 237(5):481–90
  22. Pandya KG, Patel MR, Lau-Cam CA. Comparative study of the binding characteristics to and inhibitory potencies towards PARP and in vivo antidiabetogenic potencies of taurine, 3-aminobenzamide, and nicotinamide. Journal of Biomedical Science; 2010. 17 (Suppl 1): S16
  23. Ghasemi A, Khalifi S, Jedi S. Streptozotocin-nicotinamide-induced rat model of type 2 diabetes (review). Acta Physiol Hung; 2014. 101(4):408–20
  24. Bule M, Abdurahman A, Nikfar S, Abdollahi M, Amini M. Antidiabetic effect of quercetin: A systematic review and meta-analysis of animal studies. Vol. 125. Food and Chemical Toxicology. Elsevier Ltd; 2019. 494–502
  25. Panjuantiningrum F. Pengaruh Pemberian Buah Naga Merah (Hylocereus Polyrhizus) Terhadap Kadar Glukosa Darah Tikus Putih yang Diinduksi Aloksan. Unpublished. Surakarta: Universitas Sebelas Maret; 2009
  26. Ghorbani A. Mechanisms of antidiabetic effects of flavonoid rutin. Vol. 96. Biomedicine and Pharmacotherapy: Elsevier Masson SAS; 2017. 305–12
  27. Hsu C-Y, Shih H-Y, Chia Y-C, Lee C-H, Ashida H, Lai Y-K, et al. rutin potentiates insulin receptor kinase to enhance insulin-dependent glucose transporter 4 translocation. Mol Nutr Food Res; 2014. 58(6):1168–76
  28. Hunyadi A, Martins A, Hsieh T-J, Seres A, Zupkó I. Chlorogenic Acid and Rutin Play a Major Role in the In Vivo Anti-Diabetic Activity of Morus alba Leaf Extract on Type II Diabetic Rats. PLoS One; 2012. 7(11):e50619
  29. Niture NT, Ansari AA, Naik SR. Anti-hyperglycemic activity of rutin in streptozotocin-induced diabetic rats: An Effect Mediated Through Cytokines, Antioxidants And Lipid Biomarkers. Indian J Exp Biol; 2014. 52(7):720–7
  30. Puchchakayala G. Hypoglycemic and antidiabetic activity of flavonoids : Boswellic acid, Ellagic acid, Quercetin, Rutin on Streptozotocin-Nicotinamide Induced Type 2 Diabetic. 2012. 4(2):251-256
  31. Li YQ, Zhou FC, Gao F, Bian JS, Shan F. Comparative Evaluation of Quercetin, Isoquercetin and Rutin as Inhibitors of α-Glucosidase. J Agric Food Chem; 2009. 57(24):11463–8
  32. Ahmed, Osama M.Moneim AA, Yazid IA, Mahmoud AM. Antihyperglycemic, antihyperlipidemic and antioxidant effects and the probable mechanisms of action of Ruta graveolens infusion and rutin in nicotinamide-streptozotocin-induced diabetic rats. Diabetologia Croatica; 2010. 39-1(1):15
  33. Banerjee M, Vats P. Reactive metabolites and antioxidant gene polymorphisms in Type 2 diabetes mellitus. Vol. 2. Redox Biology: Elsevier BV; 2014. 170–7
  34. Hernawati, Setiawan NA, Shintawati R, Priyandoko D. The role of Red Dragon Fruit Peel (Hylocereus polyrhizus) to Improvement Blood Lipid Levels of Hyperlipidaemia Male Mice. Journal of Physics Conference Series; 2018. 1013(1):012167
  35. Norhayati AH, Marhazlina M, Mohd Adzim KR, Rokiah MY. Effects of red pitaya fruit (Hylocereus polyrhizus) consumption on blood glucose level and lipid profile in type 2 diabetic subjects. Borneo Sci; 20. 113–29
  36. Yokomizo A, Moriwaki M. Effects of Uptake of Flavonoids on Oxidative Stress Induced by Hydrogen Peroxide in Human Intestinal Caco-2 Cells. Biosci Biotechnol Biochem; 2006. 70(6):1317–24
  37. Esmaeili MA, Zohari F, Sadeghi H. Antioxidant and protective effects of major flavonoids from teucrium polium on β-cell destruction in a model of streptozotocin-induced diabetes. Planta Med; 2009. 75(13):1418–20
  38. Kappel VD, Cazarolli LH, Pereira DF, Postal BG, Zamoner A, Reginatto FH, et al. Involvement of GLUT-4 in the stimulatory effect of rutin on glucose uptake in rat soleus muscle. J Pharm Pharmacol; 2013. 65(8):1179–86
  39. Roberts CK, Hevener AL, Barnard RJ. Metabolic syndrome and insulin resistance: Underlying causes and modification by exercise training. Compr Physiol; 2013. 3(1):1–58
  40. Meeprom A, Sompong W, Suwannaphet W, Yibchok-Anun S, Adisakwattana S. Grape seed extract supplementation prevents high-fructose diet-induced insulin resistance in rats by improving insulin and adiponectin signaling pathways. Br J Nutr; 2011. 106(8):1173–81
  41. Cao H, Hininger-Favier I, Kelly MA, Benaraba R, Dawson HD, Coves S, et al. Green tea polyphenol extract regulates the expression of genes involved in glucose uptake and insulin signaling in rats fed a high fructose diet. J Agric Food Chem; 2007. 55(15):6372–8
  42. Zhang HJ, Ji BP, Chen G, Zhou F, Luo YC, Yu HQ, et al. A combination of grape seed-derived procyanidins and gypenosides alleviates insulin resistance in mice and HepG2 cells. Journal of Food Science; 2009. 74(1): H1-7
  43. Guo S. Insulin signaling, resistance, and metabolic syndrome: Insights from mouse models into disease mechanisms. Journal of Endocrinology; 2014. 220(2): T1–T23
  44. Li RW, Theriault AG, Au K, Douglas TD, Casaschi A, Kurowska EM, et al. Citrus polymethoxylated flavones improve lipid and glucose homeostasis and modulate adipocytokines in fructose-induced Insulin resistant hamsters. Life Sci; 2006. 79(4):365–73
  45. Liao Z, Wu Z, Wu M. Cirsium japonicum flavones enhance adipocyte differentiation and glucose uptake in 3T3-L1 cells. Biol Pharm Bull; 2012. 35(6):855–60
  46. Jennings A, Welch AA, Spector T, Macgregor A, Cassidy A. Intakes of Anthocyanins and Flavones Are Associated with Biomarkers of Insulin Resistance and Inflammation in Women. J Nutr; 2014. 144(2):202–8
  47. Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine. Fifth Edition. Acta Crystallographica Section D Structural Biology; 2017. 73(4):384-385
  48. Wang Y Bin, Ge ZM, Kang WQ, Lian ZX, Yao J, Zhou CY. Rutin Alleviates Diabetic Cardiomyopathy in a Rat Model of Type 2 Diabetes. Exp Ther Med; 2015. 9(2):451–5
  49. Kamalakkannan N, Prince PSM. Rutin Improves the Antioxidant Status in Streptozotocin-Induced Diabetic Rat Tissues. Mol Cell Biochem; 2006. 293(1–2):211–9
  50. Ghiasi M, Heravi MM. Quantum Mechanical Study of Antioxidative Ability And Antioxidative Mechanism of Rutin (Vitamin P) in Solution. Carbohydr Res; 2011. 346(6):739–44

Last update:

  1. Oxidative stress in liver of streptozotocin-induced diabetic mice fed a high-fat diet: A treatment role of Artemisia annua L.

    Mahshid Ghanbari, Mohammad Shokrzadeh Lamuki, Forouzan Sadeghimahalli, Emran Habibi, Mohammad Reza Sayedi Moqadam. Endocrine Regulations, 57 (1), 2023. doi: 10.2478/enr-2023-0027
  2. Recent Studies on Strawberries

    Rushendran Rapuru, Sivakumar Bathula, Ilango Kaliappan. 2023. doi: 10.5772/intechopen.103973

Last update: 2024-06-21 04:32:58

No citation recorded.