ARTICLE INFO

Article Type

Original Research

Authors

Mojaz Dalfardi   N. (1 )
Ghodrati Azadi   H. (* )
Fathi Hafshjani   B. (1 )






(* ) Basic Sciences Department, Veterinary Medicine Faculty, Ferdowsi University of Mashhad, Mashhad, Iran
(1 ) Basic Sciences Department, Veterinary Medicine Faculty, Ferdowsi University of Mashhad, Mashhad, Iran

Correspondence

Address: Basic Sciences Department, Veterinary Medicine Faculty, Pardis of Ferdowsi University, Azadi Square, Mashhad, Iran. Postal Code: 9177948974. Post Box: 1793
Phone: +985138805631
Fax: +985138763852
ghodrati@um.ac.ir

Article History

Received:  October  31, 2014
Accepted:  February 25, 2015
ePublished:  April 14, 2015

BRIEF TEXT


… [1, 2] Citrullus Colocynthis is of the Cucurbitaceae family. Its blood glucose lowering effects have been shown. As a wild plant, Citrullus Colocynthis grows in different parts of Iran [3]. … [4] Citrullus Colocynthis includes saponins, colocynth, alkaloid, glycosides and citrullin [5]. In traditional medicine, the plant has been used in the treatment of constipation, poor bowel actions, bacterial infections, liver disease, stimulates the liver and as an antiseptic for the kidneys [6].

Citrullus Colocythis fruit increases the secretion of insulin from pancreatic cells, and in addition, this plant has antibacterial and antifungal effects [7-12]. … [13, 14]

The aim of this study was to compare between the anti-diabetic effect of Citrullus Colocythis and metformin drug on the blood glucose level.

Non-declared

250-300gr male Wister rats were studied (Animal Home of School of Pharmacy and BuAli Research Institute of Mashhad, Iran).

32 rats were randomly divided into 4 groups.

Access to water and diet were similar in all groups. In all groups, the amount of glucose and insulin was measured and recorded on the zero day of the experiment. On a normal diet 8 rats were considered negative control in a group. 24 rats experimentally underwent streptozotocin intra-peritoneal injection of 60 mg/kg (Enzo; USA) within 48 hours, repeated twice, were diagnosed diabetes type 2. On the third day of the experiment, the rats were randomly divided into three 8-rat groups including a group assigned to receive distilled water as positive control group, treated group with 14 mg/kg metformin (Aria, Iran) as a control group and the experiment group treated with 50 mg/kg of Citrullus Colocynthis fruit powder (purchased from summer 2013 fields product, and after the species had been confirmed, its fruit was ground). 28 mg/ml Metformin solution and 100 mg/ml Citrullus Colocynthis were prepared in the distilled water for daily use. Medication and plant were administrated through gavage on the mentioned regular daily dosage with the amount of 1 cc for 6 weeks. There was no limitation in water and food. Before administration of the first dose and after the last dose administration on days zero, 3, 14, 28 and 42, blood glucose was measured via the tail vein after 12-hour food deprivation, using a glucometer (EasyGlucoTM; Belgium). Blood glucose levels and weight of rats in negative control group was measured. After each blood glucose measurement, each animal was weighted and blood glucose above 250 mg/dl was considered as diabetic. Blood glucose was measured through glucose oxidase using a glucometer. Insulin measurement was performed using immunochemistry 3 days after the injection of streptozotocin and every 7 days with the kit (Diametra, Italy) detected by ELISA. Data was analyzed using SPSS 18 and One-way ANOVA with Repeated Measure Analysis.

Weight was equal for all rats in all groups, i.e. metformin, Citrullus Colocynthis, positive control and negative control groups in day zero and there was no significant difference between the groups in day zero. Weight decreased within 42 days in all groups except the negative control. On day 42, there was a significant difference between weights of the rats in metformin and negative control groups, Citrullus Colocynthis treatment and positive control groups, and negative and positive control groups. There was no significant difference in weight between other groups on day 42 (Table 1). There was no difference between all groups in the amount of insulin on days zero and three. On day 14 there was a significant difference in the amount of insulin between metformin, Citrullus Colocynthis and positive control groups and negative control group. However, there was no significant difference in the amount of insulin between metformin and Citrullus Colocynthisgroups on the day 14. On day 42, there was a significant difference in the amount of insulin between metformin, Citrullus Colocynthis and positive control groups and negative control group. However, there was no significant difference in the amount of insulin between metformin and Citrullus Colocynthis groups on day 42. The reductions in the amount of insulin on day 42 and day 3 were the same in both metformin and Citrullus Colocynthis groups. Generally, insulin efficiency of metformin was the same with that of Citrullus Colocynthis (Table 1). Glucose level was the same in all groups on day zero and there was no significant difference between them. There was a significant difference in the amount of glucose on day 3 between metformin and Citrullus Colocynthis groups and between Citrullus Colocynthis and positive control groups. In addition, there was a significant difference between metformin, Citrullus Colocynthis and positive control groups and negative control group. There was no significant difference between metformin and positive control groups, only. There was a significant difference in the amount of glucose on day 14 between metformin and Citrullus Colocynthis groups, between metformin, Citrullus Colocynthis and positive control groups and negative control group and also, between Citrullus Colocynthis and positive control groups. However, there was no significant difference between metformin and positive control groups, only. There was a significant difference in the amount of glucose on day 28 between metformin and Citrullus Colocynthis groups, between metformin and negative control and between Citrullus Colocynthis and positive control groups. In addition, there was a significant difference between Citrullus Colocynthis and positive control groups and negative control group. There was no significant difference between metformin and positive control groups, only. There was a significant difference in the amount of glucose on day 42 between metformin and positive control groups, between metformin and negative control groups and between Citrullus Colocynthis and negative control groups. In addition, there was a significant difference between Citrullus Colocynthis and positive control groups and between positive control and negative control groups. However, there was no significant difference between metformin and Citrullus Colocynthis groups. There was more glucose decrease from day 3 to day 42 in Citrullus Colocynthis group than metformin group (Table 1).

Cinnamon and insulin have synergy effects and other words, cinnamon can improve insulin effects [15]. Hydro-alcoholic extract of green tea used in doses of 50, 100, and 200 mg/kg reduces the blood glucose caused by diabetes and dose of 100 mg/kg is the most appropriate dose of this extract [16]. In the investigation of the effect of saponozid extract of Citrullus Colocynthis on the healthy rats and diabetic rats with streptozotocin, no change was seen in the blood glucose in the healthy rats, but significant decrease was observed in the blood glucose of diabetic rats and its anti-diabetic effect has been remained within 26 days after the injection. This effect becomes active again after the return to diabetes [17]. Although Citrullus Colocynthis can reduce the plasma glucose of diabetic rabbits, still no effective and safe dose has been found, and more studies are needed [18]. The pulp and seeds of Citrullus Colocynthis can reduce the level of blood glucose in the diabetic rabbits [19]. The use of Citrullus Colocynthis extract is effective on the reduction of oxidative stress, and probably can be used as an effective agent for the prevention of diabetes [8, 20-24]. Citrullus Colocynthis is safe as an antibiotic treatment [25]. Citrullus Colocynthis improved the metabolic conditions of insulin increase which is in line with other studies. Citrullus Colocynthis and insulin had synergy effects, i.e. the use of Citrullus Colocynthis increased the efficiency and amount of insulin. This conclusion is based on other studies [15]. There was no significant difference between the mean weight of rats in metformin group and Citrullus Colocynthis group, while the glucose-lowering effect was observed. However, in each of these groups alone, on the day 42, weight reduction was observed compared to day zero. These results are in line with other researches [25].

To find the right dosage and safety as well as to evaluate the possible side effects, further study needs to be done. Other animals, as well as the mechanisms and cellular effects of Citrullus Colocynthis and pathological studies, should be studied.

Citrullus Colocynthis gastrointestinal complications resulting from consumption of Citrullus Colocynthis was of the limitations of this study.

Citrullus Colocynthis fruit powder can be effective in controlling the amount of blood glucose comparing to metformin and its application as herbal compound can increase the amount of blood glucose and less chemical drugs utilization. Therefore, it can improve the health status and makes the effects of the drugs lower.

Researchers appreciate the Research Center of Ferdowsi University of Mashhad.

Non-declared

All procedures were approved by Ethics Committee of the university and according to the law of use and care of the laboratory animals.

The Research Deputy of Ferdowsi University of Mashhad paid the costs.

TABLES and CHARTS

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CITIATION LINKS

[1]Dallak M, Bin-Jaliah I. Antioxidant activity of Citrulus colocynthis pulp extract in the RBC’s of alloxan- induced diabetic rats. Pak J Physiol. 2010;6(1):1-5.
[2]Arise RO, Malomo SO, Adebayo JO, Igunnu A. Effects of aqueous extract of Eucalyptus globules on lipid peroxidation and selected enzymes of rat liver. J Med Plants Res. 2009;3(2):77-81.
[3]Zahrani HS, Amer KH. A comparative study on citrullus colocynthis plants grown in different altitudinal location in Saudi Arabia. American-Eurasian J Sci Res. 2006;1(1):1-7.
[4]Ziyyat A, Legssyer A, Mekhfi H, Dassouli A, Serhrouchni M, Benjelloun W. Phytotherapy of hypertension and diabetes in oriental Morocco. J Ethnopharmacol. 1997;58(1):45-54.
[5]Rahbar AR, Nabipour I. The hypolipidemic effect of Citrullus colocynthis on patients with hyperlipidemia. Pak J Biol Sci. 2010;13(24):1202-7.
[6]Mardani M, Rezapour S, Rezapour P. The role of Citrullus colocynthis in the control and treatment of diabetes mellitus. J Nurs Midwifery, Lorestan Univ Med Sci. 2008;4(10-11):37-44. [Persian]
[7]Shafaei H, Soleimani Rad J, Mahdavi R, Ostad Rahimi AR, Rezazadeh H, Argani H, et al. The potentiating effects of Citrullus colocynthis extract on immune system. Med J Tabriz Univ Med Sci. 2007;29(2):77-82. [Persian]
[8]Khalil M, Mohamed G, Dallak M, Al-Hashem F, Sakr H, Refaat A, et al. The effect of Citrullus colocynthis pulp extract on the liver of diabetic rats a light and scanning electron microscopic study. American J Biochemistry Biotechnology. 2010;6(3):155-63.
[9]Marzouk B, Marzouk Z, Décor R, Edziri H, Haloui E, Fenina N, et al. Antibacterial and anticandidal screening of Tunisian Citrullus colocynthis Schrad. from Medenine. J Ethnopharmacol. 2009;125(2):344-9.
[10]Benalla W, Bellahcen S, Bnouham M. Antidiabetic medicinal plants as a source of alpha glucosidase inhibitors. Curr Diabetes Rev. 2010;6(4):247-54.
[11]Barri ME, Onsa TO, Elawad AA, Elsayed NY, Wasfi IA, Abdul-Bari EM, et al. Toxicity of five Sudanese plants to young ruminants. J Comp Pathol. 1983;93(4):559-75.
[12]Dehghani F, Panjehshahin MR. The toxic effect of alcoholic extract of Citrullus colocynthis on rat liver. Iranian J Pharmacol Ther. 2006;5(2):117-19.
[13]Mahmoodi M, Sayyadi AR, HosseiniZijoud SM, Hajizadeh MR, Kazemi Arababadi M, Asadikaram GR, et al. Survey on the effects of different concentrations of Citrullus colocynthis fruit powder on some of the blood biochemical factors in normal and diabetic male rats. J Rafsanjan Univ Med Sci. 2012;11(1):11-20. [Persian]
[14]Rendell M. Dietary treatment of diabetes mellitus. New England J Med. 2000;342(19):1440-1.
[15]Gheibi N, Parvizi MR, Jahani Hashemi H. The effect ofcinnamon on glucose concentration of diabetic rats in presence or absence of insulin. J Ghazvin Univ Med Sci. 2005;9(3):3-7. [Persian]
[16]Mehdizade M, Hosseini SA, Ebrahiminia F, Elahi A, Fallah Hosseini H, Azizi M, et al. Effect of green tea (Camellia sineisis L.) extract on blood glucose and body weight in male induced diabetic rats. J Gorgan Univ Med Sci. 2009;11(1):8-12.
[17]Benmehdi H, Azzi R, Djaziri R, Lahfa F, Benariba N, Tabti B. Effect of saponosides crude extract isolated from Citrullus colocynthis (L.) seeds on blood glucose level in normal and streptozotocin induced diabetic rats. J Med Pharm Sci. 2011;5(31):6864-8.
[18]Zamani M , Rahimi AO, Mahdavi R, Nikbakhsh M, Jabbari MV, Rezazadeh H, et al. Assessment of antihyperlipidemic effect of Citrullus colocynthis. Revista Brasileira de Farmacognosia. 2007;17(4):492-6.
[19]Dashti N, Zamani M, Mahdavi R, Ostad Rahimi A. The effect of citrulluscolocynthis on blood glucose profile level in diabetic rabbits. J Jahrom Univ Med Sci. 2012;9(1):27-32.
[20]Zareei Mahmoudabadi AB, Fallahhossini F, Sharifabady R, Nourouzzadeh A, Imani H, Ghoshouni H. The effect of Citrullus colocynthis Extract on the preventing/reducing streptozotocin-induced diabetes in rat. Kowsar Med J. 2007;12(1):13-20.
[21]Goldfain D, Lavergne A, Galian A, Chauveinc L, Prudhomme F. Peculiar acute toxic colitis after ingestion of colocynth: A clinicopathological study of three cases. Gut. 1989;30(10):1412-8.
[22]Fallah Huseini H, Heshmat R, Larijani B, Fakhrzadeh H, Jafariazar Z, Darvishzadeh F, et al. The clinical investigation of Citrullus colocynthis (L.) Schrad. fruit in treatment of type II diabetic patients; a randomized, double-blind, placebo-controlled study. J Med Plants. 2006;1(Suppl2):31-5. [Persian]
[23]Larrey D. Hepatotoxicity of herbal remedies. J Hepatol. 1997;26(Suppl1):47-51.
[24]Adam SE, Al-Yahya MA, Al-Farhan AH. Combined toxicity of Cassia senna and Citrullus colocynthis in rats. Vet Hum Toxicol. 2001;43(2):70-2.
[25]Atole SK, Jangde CR, Philip P, Rekhe DV, Aghav DV, Waghode HJ, Chougule AM. Safety evaluation studies of Citrullus colocynthis for diabetes in rats. Vet World. 2009;2(11):423-5.