Jurnal Gizi Indonesia (The Indonesian Journal of Nutrition) Jurnal Gizi Indonesia Vol. 10, No. 1, December 2021 (6-14) Submitted: 8 October 2020, Accepted: 9 April 2021 Online https://ejournal.undip.ac.id/index.php/jgi 1 Masters Program in Clinical Nutrition and Nutrition Sciences, Universitas Sebelas Maret 2 Department of Nutrition, Faculty of Medicine, Universitas Sebelas Maret 3 Department of Public Health, Faculty of Medicine, Universitas Sebelas Maret *Correspondence: e-mail: mahendrideayu@gmail.com Copyright © 2021; Jurnal Gizi Indonesia (The Indonesian Journal of Nutrition), Volume 10 (1), 2021 e-ISSN : 2338-3119, p-ISSN: 1858-4942 Red dragon fruit juice in reducing ros levels and insulin resistance In rats with type 2 diabetes mellitus model Mahendri Deayu Putri 1* , Budiyanti Wiboworini 2 , Paramasari Dirgahayu 3 ABSTRACT 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. Keywords: HOMA-IR; Red Dragon Fruit; Type 2 Diabetes Mellitus BACKGROUND Red Dragon fruit (RDF) is a fruit source that is rich in natural antioxidants, namely betacyanin, flavonoids, polyphenols, ascorbic acid, and also fiber 1 . The main antioxidant content in RDF is flavonoids. Flavonoids have a polyphenolic structure which is found in many fruits 2 . Increasing RDF flesh consumption leaves the skin that is currently not used optimally. Apart from the flesh, RDF skin can also be used as an alternative because of its nutritional content and antioxidant effects 3 . The total content of polyphenols and flavonoids from 80% methanol extract of RDF skin is three times higher than RDF flesh. The total phenolic content extracted from the skin and flesh is 14.82 ± 1.07 and 4.91 ± 0.55 mg Gallic Acid Equivalent (GAE) / 100g 4 . In type 2 diabetes mellitus (T2DM), hyperglycemia is caused by the inability of Insulin to mobilize blood glucose into cells due to insulin receptor resistance 5 . Hyperglycemia increases the auto-oxidation of glucose from free radicals. In hyperglycemia conditions, the formation of free radicals or Reactive Oxygen Species (ROS) comes from glucose oxidation, on-enzymatic glycosylation of proteins, and oxidative degradation of glycolic proteins 6 . The increase in intracellular glucose causes an abundance of electron donors to be generated during the Kreb cycle, thereby pushing the potential of the inner mitochondrial membrane upward - a condition associated with mitochondrial dysfunction and increased production of ROS 7 . In addition, ROS will increase the expression of Tumour Necrosis Factor-α (TNF-α) and exacerbate oxidative stress. TNF-α can result in insulin resistance through decreased autophosphorylation (auto-phosphorylation) of insulin receptors 8,9 . These oxidative stress markers can be measured using Malondialdehyde (MDA) 10 .