Sys Rev Pharm 2020;11(9):774-778 A multifaceted review journal in the field of pharmacy 774 Systematic Reviews in Pharmacy Vol 11, Issue 9, Sep-Oct 2020 Antidiabetic Activity of Papaya Leaf Extract (Carica Papaya L.) Isolated with Maceration Method in Alloxan- Induces Diabetic Mice Tridiganita Intan Solikhah * , Boedi Setiawan, Dilian Ramdana Ismukada Department of Veterinary Clinic, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia. *Corresponding Author: Tridiganita Intan Solikhah, Department of Veterinary Clinic, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia; E-mail: tridiganita-intan-s@fkh.unair.ac.id. ABSTRACT Introduction: Diabetes mellitus is a metabolic disorder disease that is often found in the world. Treatment with natural products can be an effective alternative in treating diabetes mellitus. Papaya (Carica papaya) has many pharmacological activities that have potential as an antidiabetic. Objective: This study aimed to determine the content of compounds in the papaya leaf ethanol extract and the effect of papaya leaf ethanol extract (Carica papaya L.) on the blood sugar level of diabetic mice induced by alloxan. Methods: The mice were adapted for 7 days and were induced on the 8 days with 180 mg/kg alloxan intraperitoneally. Papaya leaf ethanol extract (Carica papaya L.) was given for 14 days at a dose of 250, 500, and 1000 mg/kg body weight and was compared to distilled water and alloxan only as negative control and glibenclamide at a dose of 2 mg/kg body weight as the positive control. Blood samples were collected on day 1, 7, and 14 to evaluate blood glucose levels before and after treatment. Results: The compounds contained in the ethanol extract of papaya leaf include alkaloids, flavonoids, triterpenoids, tannins, and saponins. The administration of papaya leaf ethanol extract with 3 doses and glibenclamide at a dose of 2 mg/kg body weight could reduce blood glucose levels in diabetic Wistar mice induced by alloxan. The administration at a dose of 1000 mg/kg body weight of papaya leaf ethanol extract is more effective in reducing blood glucose levels in diabetic Wistar mice compared to 2 mg/kg body weight of glibenclamide. Conclusion: Induction of Carica papaya leaf extracts decreased blood sugar levels but cannot effectively increased the body weight in diabetic mice. Keywords: Antidiabetic, Ethanol Extract, Carica papaya L., Wistar Mice, Alloxan Correspondence: Tridiganita Intan Solikhah Department of Veterinary Clinic, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia. E-mail: tridiganita-intan-s@fkh.unair.ac.id. INTRODUCTION Diabetes is a metabolism disorder that found in human and animal. The most frequent in diabetes is type 2 diabetes (1,2) , whereas this disorder tends to increase by the year. Moreover, one of the most important factors in diabetes treatment is controlling in blood glucose levels with close attention to the nutrients consumed, including the type of food that cause increased blood sugar (3,4). Organisms with diabetes mellitus are usually treated with modern medicine, which is consisted of oral hypoglycemic medicine, insulin injection, and other antidiabetic injections (5). Glibenclamide is a medicine from sulfonylurea group that is often used to type 2 diabetes treatment (6,7). However, this medicine has several adverse effects (8,9). Side effects including hypoglycemia, nausea, and skin reactions such as erythema multiforme, exfoliative . Occasionally, they can cause abnormalities in liver function tests, which may rarely lead to cholestatic jaundice, hepatitis and hepatic failure (6,31). Using glibenclamide frequently can cause fatal hypoglycemia and liver abnormalities. Therefore, the treatment with alternative medicine become an innovation in the antidiabetic medicines development with no side effects. Based on the abundant natural product potential in Indonesia, exploration is needed to find alternative medicine as antidiabetic (10,11). One of the plants that can be utilized as an antidiabetic medicine is papaya (Carica papaya) with its leaf as an antidiabetic agent. Several previous studies reported that Carica papaya leaf has the potential to become an antidiabetic medicine. Juárez-Rojop et al. (2014) revealed that the Carica papaya leaf had a hypoglycemic effect on mice induced with streptozotocin (STZ) (12). The results of Airaodion et al. (2019) extract of Carica papaya leaf had a hypoglycemic effect on mice induced with alloxan (13). Based on this previous result, this study attempt to innovate with the use of ethanol solvent and maceration method to obtain Carica papaya leaf extract. Moreover, the Carica papaya leaf extract in this study was extracted using the maceration for application on a large scale and easy to use by the community. Therefore, this study investigated Carica papaya leaf extract obtained through the maceration method on the hypoglycemic effect in mice induced with alloxan. MATERIALS AND METHODS Animals The animals used in this study were Wistar mice weighing between 25-35 g. The mice were acclimation for 7 days. They were placed into the cage, given clean water ad libitum and standard commercial pellet feed. Ethical code, institutional and national regulation on live animals were strictly observed. Animals used in this study received ethical approval from Health Research Ethical Clearance Commission Faculty of Dental Medicine