Background: Citrullus colocynthis L. is a member of the family Cucurbitaceae. It is widely available in Sudan and traditionally used for treatment of skin infections, diabetes and constipation worldwide.
Objectives: This study aimed to investigate the effects of ethanolic extract of C. colocynthis fruit pulp on blood glucose level in normal fasting rats.
Method: Two groups of rats, each of twenty one were used to study the effects of the extract (300 mg/kg/ml) on fasting blood glucose level (BGL) and glucose tolerance test (GTT).
Results: The oral administration of ethanolic extract of C. colocynthis fruit pulp resulted in a sudden drop in BGL of normal fasting rats after four hours. This was accompanied by some toxic effects appeared as severe diarrhea, followed by deaths of some rats (2/7). Moreover, the administration of the extract did not exhibit a remarkable reduction or improvement in the induced hyperglycemia.
&nbsp;Conclusion: This study showed that, ethanolic extract of C. colocynthis fruit pulp reduced the BGL without significant hypoglycemic effect and the extract appeared to be highly toxic.

Babiker, Hanaa A.

M, Abd Elwahab H.

Taj Eldin, Imad M.

English

Journals Of University Of Gezira

Gezira Journal Of Health Sciences 2012 vol.8(2)   EDITORIAL  Gezira Journal Of Health Sciences 2012 vol.8(2)   The Effects of Ethanolic Extract of Handal (Citrullus colocynthis L.) Fruit Pulp on Blood Glucose level in Normal Fasting Rats  Hanaa A. Babiker1 , Imad M. Taj Eldin1 and Abd Elwahab H.M2  1Department of Pharmacology, Faculty of Pharmacy, University of Gezira, Sudan 2Department of Pharmacology and Toxicology, Medicinal and Aromatic Plant Research Institute, National Center for Research, Sudan Corresponding author email: hannoab@hotmail.com  Abstract Background: Citrullus colocynthis L. is a member of the family Cucurbitaceae. It is widely available in Sudan and traditionally used for treatment of skin infections, diabetes and constipation worldwide. Objectives: This study aimed to investigate the effects of ethanolic extract of C. colocynthis fruit pulp on blood glucose level in normal fasting rats. Method: Two groups of rats, each of twenty one were used to study the effects of the extract (300 mg/kg/ml) on fasting blood glucose level (BGL) and glucose tolerance test (GTT).  Results: The oral administration of ethanolic extract of C. colocynthis fruit pulp resulted in a sudden drop in BGL of normal fasting rats after four hours. This was accompanied by some toxic effects appeared as severe diarrhea, followed by deaths of some rats (2/7). Moreover, the administration of the extract did not exhibit a remarkable reduction or improvement in the induced hyperglycemia.  Conclusion: This study showed that, ethanolic extract of C. colocynthis fruit pulp reduced the BGL without significant hypoglycemic effect and the extract appeared to be highly toxic..  Keywords: Citrullus colocynthis, fruit pulp, fasting blood glucose, glucose tolerance test.  Introduction Traditional use of medicines is recognized as a way to learn about potential future medicines. By the year 2001, researchers identified 122 compounds used in mainstream medicine, which were derived from ethnomedical plant sources; 80% of these compounds were used in the same or related manner as the traditional ethnomedical use [1]. Many medicinal plants synthesize substances that are useful to the maintenance of health in humans and other animals. These include, for example, alkaloids and phenolic compounds that serve as plant defense mechanisms against predation by microorganisms, insects, and Gezira Journal Of Health Sciences 2012 vol.8(2)   EDITORIAL  Gezira Journal Of Health Sciences 2012 vol.8(2)   herbivores [2-3]. Although many consumers believe that herbal medicines are safe, because they are natural, herbal medicines and synthetic drugs may interact, causing toxicity and adverse effects to the patient [4].  Furthermore, adulteration, inappropriate formulation, or lack of understanding of plant and drug interactions have led to adverse reactions that are sometimes life threatening or lethal [5]. Thus, proper trials and studies are needed to determine the safety and efficacy of each plant before they can be recommended for medical use [6].  Citrullus colcynthis L. Schrad is a member of the family Cucurbitaceae. This plant commonly known as colocynth, bitter apple, bitter cucumber, egusi or vine of Sodom. It is native to dry areas of North Africa, being common throughout the Sahara, areas of Morocco, Egypt and Sudan, eastward through Iran to India and other parts of tropical Asia [7]. The different parts of the plant (seeds, leaves, fruit pulp and fruit rind) had been studied, and the main active constituents were identified. The seeds are rich in fatty acids such as myristic, palmitic, stearic, oleic, linoleic and linolenic acid. The main active phytoconstituent present in the pulp is phytosterol glycoside (citrullol). The other glucoside cucurbitacins including elaterinide and cucurbitacine E, cucurbitacine B, other glycosides liberating cucurbitacines I and L, alkanes, aliphatic alcohols, alkaloids and choline base. The bitter substances are colocynthin and colocynthetin [8]. The dried pulp of C. colcynthis fruit was used as a traditional medicine in the Sudan, mostly for skin infections, edema and, in some instances, for diabetes. It has been also used for constipation worldwide [9] however, the ingestion of the cathartic fruit can have many undesired effects, including bloody diarrhea and even true acute toxic colitis and changes in the colon similar to these seen with other laxative abuse [10-12]. In East Africa, the seed tar was used by nomads in traditional medications applied to the skin [13]. In some Arab countries (United Arab Emirates and Morocco) the seeds are used to treat diabetes. However, when the chloroform and methanol extracts of seeds and ethanol extracts of leaves and pulp of C. colocynthis were investigated in normal and diabetic streptozotocin- induced rats, neither the seeds extract nor the leaf extract had any effect on fasting glucose levels in normal or diabetic rats, and they had no effect in the oral glucose tolerance test [14]. Many workers suggested that the fruits of C. colcynthis possess antitumor activity [15]. This study was designed to investigate the effects of ethanolic extract of C. colocynthis fruit pulp on blood glucose levels in normal fasting rats.   Materials and Methods: Plant material Fresh ripe fruits of C. colocynthis were purchased from the local market in Wad Medani city, Gezira State, Central Sudan, in April, 2010. The species was botanically authenticated and herbarium specimens were deposited at the National Herbarium, Medicinal and Aromatic Plants Research Institute, National Centre for Researches (NCR), Khartoum, Sudan.  The ripe fruits were peeled to separate the rind (epicarp and outer most layer of mesocarp). Mature black seeds were separated manually from the pulp. Then, the pulp was dried and minced with a grinder into a powder.  Gezira Journal Of Health Sciences 2012 vol.8(2)   EDITORIAL  Gezira Journal Of Health Sciences 2012 vol.8(2)   Extraction of the plant material The pulp powder of C. colocynthis (250 g) was macerated in 1.5 L ethanol (99%) and stirred continuously for 48 hours at room temperature. The mixture was filtered using Bukhner fennel under vacuum, then the extract was evaporated to dryness at room temperature in a large porcelain dish to give yellowish material (yield=51.7 g). The residue was dissolved in distilled water to obtain the desired concentration. The effects of ethanolic extract of C. colocynthis fruit pulp (300 mg/kg/ml) on BGL in normal fasting rats Experimental animals The experiment was carried out according to the method developed by Tayyba Zia et al., 2001[16]. Animals used were twenty one Albino rats weighing 170 – 200g, housed in a clean animal house and subjected to especial nutritional program. Animals were acclimatized for a period of 7 days under standard environmental conditions. They were divided into three groups each of seven rats and submitted to fasting for 18 hours before the study. Group I (negative control) administered water (1 ml), group II (positive control) received glibenclamide (5 mg/kg/ml) and group III (test group) given the ethanolic extract of C. colocynthis fruit pulp (300 mg/kg/ml). The water, glibenclamide water suspension and the extract were administered to the rats using intragastric tubes.   Determination of fasting blood glucose levels  After treatment, blood samples were collected from the tail vein of each rat separately. BGLs were determined using an electronic glucometer, Glucose plus (Halpern, Quebec, Canada) at 0, 1, 2, and 4 hours (Table 1).  Oral glucose tolerance test of ethanolic extract of C. colocynthis (300 mg/kg/ml) in normal fasting rats Oral glucose tolerance test (OGTT) was performed according to the method developed by Wasfi, 1994[14]. Twenty one Albino rats were divided into three groups, each of seven. Basal BGLs were determined from blood samples taken from tail-tips of each rat. Then glucose load of 1 g/kg body weight was given first to the three groups of rats. This was followed by water (1 ml) for group I (negative control), glibenclamide (5 mg/kg/ml) for group II (positive control) and ethanolic extract of C. colocynthis (300 mg/kg/ml) for group III (test group). BGLs were determined at 0, 1, 2 and 4 hours using an electronic glucometer. Data analysis The obtained data were expressed as means ± standard error of means (SEM) and analyzed using analysis of variance (ANOVA). Comparisons with the control groups were made using One-way ANOVA. Differences were considered significant, if P-value <0.05.      Results and Discussion: There is an increasing tendency for traditional medicine in the world. Many people prefer to take herbal products instead of chemical medicines. However, over consumption of herbal medicines has led to many Gezira Journal Of Health Sciences 2012 vol.8(2)   EDITORIAL  Gezira Journal Of Health Sciences 2012 vol.8(2)   unpredictable side effects. One of these traditional medicines is C. colocynthis, which is used by diabetic patients as a hypoglycemic agent. This study was conducted to study the possible hypoglycemic effects of ethanolic extract of C. colocynthis fruit pulp (300 mg/kg/ml) on BGLs in normal fasting rats.   Effect of ethanolic extract of C. colocynthis (300 mg/kg/ml) on the BGLs in normal fasting rats The ethanolic extract of C. colocynthis resulted in significant (P=0.001) but abrupt reduction in the fasting BGL of normal rats by 50.33 mg/dl. However, this reduction was abnormal in that, it was sudden and occurred only after four hours. When this reduction was compared to that produced by glibenclamide, it was found that the reduction obtained by glibenclamide was significant (P=0.001), normal and showing gradual manner of reduction (42.6 mg/dl), four hours later (Table 1). It was also noted that, the same dose (300 mg/kg) that produced this abrupt reduction in the BGL, appeared to be extremely toxic, developing severe diarrhoea, dullness and ruffled hair. Diarrhoea was a prominent sign of C. colocynthis poisoning [17]. Some of the treated rats in the test group were died (2/7) within the four hours of the experiment.  Table1: Effects of oral administration of water (1 ml), glibenclamide (5 mg/kg/ml) and ethanolic extract of C. colocynthis (300 mg/kg/ml) on the blood glucose levels in normal fasting rats  P. value Reduction of Glycemia (mg/dL) BGLs (mg/dL, mean±S.E.M)  Treatment 4h 2h 1h 0h 0.339 5.5 80.5±3.01 79.83±1.52 84.33±3.67 86±2.25 Water 0.001 42.6 45.2±3.12 50.17±3.17 62±6.15 87.8±4.03 Glibenclamide 0.001 50.33 47.67±1.5 81.67±2.16 96±2.6 98±3.5 C. colocynthis Gezira Journal Of Health Sciences 2012 vol.8(2)   EDITORIAL  Gezira Journal Of Health Sciences 2012 vol.8(2)    Figure 1: Effects of oral administration of water (1 ml), glibenclamide (5 mg/kg/ml) and ethanolic extract of C. colocynthis (300 mg/kg/ml) on the blood glucose levels in normal fasting rats        Glucose tolerance test of ethanolic extract of C. colocynthis (300 mg/kg/ml) in normal fasting rats Results obtained showed that the administration of 1 g/kg glucose caused an increase in BGLs (hyperglycemic peak) in normal fasting rats in the first hour. It was also found that the administration of C. colocynthis extract did not exhibit a remarkable reduction or improvement in the induced hyperglycemia and a slight reduction (26.33 mg/dl) was observed in the first three hours (Table 2).   Table 2: Effects of oral administration of water (1 ml), glibenclamide (5 mg/kg/ml) and ethanolic extract of C. colocynthis (300 mg/kg/ml) on glucose tolerance test in normal fasting rats  Reduction of Glycemia (mg/dL) BGLs (mg/dL, mean)  Preparation 3h 2h 1h 0h 49 66±2.12 59±1.5 115±3.7 62±2.22 Water 25 64±3.12 71±3.17 89±5-15 78±4.03 Glibenclamide 26.33 81±1.9 84±2.1 107.33±2.2 87±1.7 C. colocynthis   0204060801001200 h 1 h 2 h 4 hTime (hours)Blood glucose level (mg/dl)WaterGlibenclamideC. colocynthisGezira Journal Of Health Sciences 2012 vol.8(2)   EDITORIAL  Gezira Journal Of Health Sciences 2012 vol.8(2)    Figure 2: Effects of oral administration of water (1 ml), glibenclamide (5 mg/kg/ml) and ethanolic extract of C. colocynthis (300 mg/kg/ml) on glucose tolerance test in normal fasting rats.  The present study demonstrated a reduction in BGL followed the oral administration of the ethanolic extract of C. colocynthis fruit pulp. However, the pattern of the reduction was not normal, compared to the standard drug, glibenclamide, because it was accompanied by severe diarrhea and deaths of some animals (2 out of 7). The occurrence of these toxicities may reflect that, the reduction in BGL may be considered as a part of the toxic effects of the plant and not an advantage.  It is known that traditional medicine and ethnobotanical information play an important role today as subjects for scientific research. The results of such assessment can provide a number of plants, which can claim priority to be investigated for a selected biological activity or efficacy against selected disorders or diseases. Thus, phytochemical screening is needed to separate phytoconstituents responsible for beneficial and/or toxic effects.  In conclusion some toxic effects C. colocynthis, rather than hypoglycemic effects were evident.  Because of the popularity of this plant in traditional medicine for treatment of some diseases such as diabetes mellitus, people should be informed of the potential toxic effects.  In addition, further investigations are required to elucidate the mechanisms through which the toxic effects and the reduction in BGL occurred.  References: 1. Fabricant DS, and Farnsworth NR (2001). The value of plants used in traditional medicine for drug discovery 109: 69-75. Fact sheet no. 134: Traditional medicine". World Health Organization, 2008-12-01. Retrieved 2009-05-02. 0204060801001201400h 1h 2h 3hTime (hours)Blood glucose level (mg/dl)WaterGlibenclamideC. colocynthisGezira Journal Of Health Sciences 2012 vol.8(2)   EDITORIAL  Gezira Journal Of Health Sciences 2012 vol.8(2)   2. Lai PK, and Roy J (2004).  Antimicrobial and chemopreventive properties of herbs and spices 11 (11): 1451-1460. 3. Tapsell LC, Hemphill I, and Cobiac L, (2006). 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Pecular acute toxic colitis after ingestion of colocynthi; a dinicopathological study of three cases. Gut 30: 1412– 1418. 11. Al Faraj S. (1995). Haemorrhagic colitis induced by Citrullus colocynthis. Annual Tropen Parasitology 89 (6): 695– 696. 12. Habs M., Jahn S.A. and Schmahi, D. (1984). Carcinogenic activity of condensate from coloquint seeds (Citrullus colocynthis) after chronic epicttaneous administration to mice. Journal of Cancer Research and Clinical Oncology 108 (1): 154–156. 13. Ziyyat A., Legssyer A. and Mekhfi, H. (1997). Phytotherapy of hypertension and diabetes in oriental Morocco. Journal of Ethnopharmacology 58 (1): 45–54. 14. Wasfi I. A. (1994). Some pharmacological studies on Citrullus colocynthis. Journal of Herbs, Spices and Medicinal Plants 212: 65–79. 15. Faust R.E., Gwaline G.E., Ramsted E.J., Whiting D.A. and Yousif N.J. (1989). Cucurbitacin glycosides from Citrullus colocynthis. Phytochemistry and Pharmaceutical Association 47(1): 325-330. 16. 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The Effects of Ethanolic Extract of Handal (Citrullus colocynthis L.) Fruit Pulp on Blood Glucose level in Normal Fasting Rats

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The Effects of Ethanolic Extract of Handal (Citrullus colocynthis L.) Fruit Pulp on Blood Glucose level in Normal Fasting Rats

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