Jundishapur J Nat Pharm Prod. 2016 August; 11(3):e33214. Published online 2016 August 28. doi: 10.17795/jjnpp-33214. Research Article Eﬀects of Hydro-Alcoholic Leaf Extract of Citrullus colocynthis on Biochemical Factors and Histopathological Changes in Streptozotocin-Induced Diabetic Rats Esmaeel Ebrahimi, 1 Ghorban Mohammadzadeh, 2,* Esraﬁl Mansouri, 3 and Mohammad Aberomand 4 1 Diabetes Research Center, Health Research Institute, Department of Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran 2 Hyperlipidemia Research Center, Department of Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran 3 Cellular and Molecular Research Center, Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran 4 Toxicology Research Center, Department of Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran * Corresponding author: Ghorban Mohammadzadeh, Hyperlipidemia Research Center, Department of Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran. Tel: +98-91134368125, Fax: +98-6113332036, E-mail: mohammadzadeh@ajums.ac.ir Received 2015 September 16; Revised 2016 April 20; Accepted 2016 April 30. Abstract Background: Diabetes mellitus is the most common leading cause of cardiovascular-related mortality and morbidity worldwide. Citrullus colocyn- this (C. colocynthis) belongs to the Cucurbitaceae family and has been used as an anti-diabetic treatment in traditional medicine. Objectives: The aim of this study was to assess the eﬀects of hydro-alcoholic leaf extract of C. colocynthis on the serum biochemical factors and histopathological changes in streptozotocin-induced diabetic rats. Methods: The current experimental study was performed on 24 male rats, which became diabetic with 60 mg/kg body weight intraperitoneal in- jection of streptozotocin (STZ). The animals were divided into four groups: untreated healthy controls, healthy controls treated with the extract, untreated diabetic and diabetic treated with extract, respectively. The animals were treated with 75 mg/kg body weight orally hydro-alcoholic leaf extract of C. colocynthis for 3 weeks. Results: The results indicated that fasting blood sugar (FBS), triglycerides (TG), low-density lipoprotein (LDL), total cholesterol, aspartate amino- transferase, alanine aminotransferase, creatinine, urea, and bilirubin (total and conjugated) in diabetic rats treated with the extract signiﬁcantly decreased compared to the other groups. Conversely, high-density lipoprotein (HDL) and serum albumin were signiﬁcantly increased in diabetic rats treated with extract. Histopathological ﬁndings showed STZ-induced diabetic complications in the pancreas, kidney and liver were improved following treatment with hydro-alcoholic leaf extract of C. colocynthis. Conclusions: The administration of hydro-alcoholic leaf extract of C. colocynthis had a signiﬁcant anti-hyperglycemic and anti hyperlipidemic eﬀect and improved diabetic complications. In addition, Citrullus C. leaf extract may have a protective eﬀect on the liver, kidneys, and pancreas. Keywords: Diabetes Mellitus, Histopathology, Streptozotocin, Lipid Proﬁle, Citrullus colocynthis 1. Background Diabetes mellitus is a chronic disease characterized by persistent hyperglycemia. Recently, the prevention of di- abetes and its complications, particularly the associated cardiovascular mortality and morbidity, has become a ma- jor health problem worldwide (1, 2). Despite the beneﬁ- cial eﬀects of anti-hyperglycemic drugs and insulin sen- sitizers, bothersome side eﬀects remain, including hypo- glycemia at high doses, a lower oral bioavailability, and in- activation by several enzymes; therefore, the development or discovery of other alternative medications is necessary (3). The use of phytotherapy, in which diﬀerent parts of plants, such as the leaves, roots, stems, ﬂowers, bark, or their active compounds, are used to prevent and treat dis- eases, is increasing globally (4). In fact, the use of tradi- tional medicinal plants that produce a hypoglycemic eﬀect has been increasing in all populations. More than 400 tra- ditional plant treatments for diabetes mellitus have been reported, but only a few of these have been investigated for their medical eﬃcacy (5). Citrullus colocynthis (C. colocynthis), often known as bit- ter melon, belongs to the Cucurbitaceae family, which grows in Arab countries, Africa, and the Middle East and is used traditionally as an anti-diabetic medication. A peren- nial plant that grows in desert and arid conditions, its fruit is initially green and then turns yellow as it ripens (6, 7). C. colocynthis contains diﬀerent chemical compounds; for example, unripe fruit has parahydroxy benzyl ester, and its roots are rich in hentriacontane elaterium; the seeds have methionine, cysteine, oleic, linoleic, linolenic, ﬁber, potassium, saponins, phosphorus and iron, but the major component is a tetracyclic terpene named cucurbitacin (8, 9), which is the main biochemical composition from the Cucurbitacin family. It is very bitter and chemically clas- siﬁed as a steroid. A study about the biological eﬀects of Copyright © 2016, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.