In vivo, Acute, Normo-hypoglycemic, Antihyperglycemic, Insulinotropic Actions of Orally Administered Ethanol Extract of Citrullus colocynthis (L.) Schrab Pulp

Abstract

Problem statement: Citrullus colocynthis (L.) Schrab (cucurbitaceae family) (Handal) is a fruit commonly known as bitter apple or bitter cucumber. Traditionally, Citrullus colocynthis has been used for the treatment of diabetes. In particular, the acute effect and rout of administration of ethanol extract of the seedless pulp in vivo remains untested. We investigated the effect of different routs of administration and their hypoglycemic and insulinotropic effects of ethanol/water (20/80 V/V) extract of the dried seedless pulp of Citrullus colocynthis (L.) Schrab on normal and alloxan-induced diabetic rats. Approach: Rats were divided into two groups, normal and diabetic rats. Non-diabetic rats were fasted for 18 h before the beginning of the experimental procedure. About 250 μL of normal saline (i.e., vehicle) was administered to control groups either i.p. (Group I) or orally (Group III) using modified feeding canula. As 250 μL pulp extract was administered i.p. (Group II) or orally (Group IV). Five min, after the administration of the extract or vehicle, an Intraperitoneal Glucose Tolerance Test (IPGTT) was conducted (1.5 g glucose/kg) on groups I, II, III and IV, but not Groups V or VI. Alloxan-induced diabetic rats were fasted for 6 h before the beginning of the experimental procedure. They were divided into control (Group V) and treated groups (Group VI), each of 6 rats. As 250 μL of the extract (equivalent to 300 mg kg^-1) was administered orally to alloxan treated-group, while 250 μL of the vehicle was administrated orally to the animals of control group. Serum samples were collected at 0, 1, 2, 3, 4 and 6 h following the treatment and were used for glucose and insulin determination. Results: Oral, but not intraperitonial (i.p.) administration of ethanol extract (300 mg kg^-1) resulted in acute, significant (p<0.05) and time-dependent changes in rat serum glucose and insulin levels in both normal and alloxan-induced diabetic rats. In extract-treated alloxan-free rats, a maximum of 32.9% reduction in serum glucose levels was observed following Intraperitonial Glucose Tolerance Test (IPGTT) using glucose-oxidase assay. A maximum reciprocal increase of 59.5% in serum insulin levels following IPGTT was determined by ELISA. Further, in alloxan/ethanol extract-treated group, a maximum of 31% reduction in serum glucose levels as well as 370.2% increase in serum insulin levels following IPGTT were observed. Conclusion: These results demonstrated that oral administration of the ethanol extract of the dried seedless pulp of Citrullus colocynthis had normo-hypoglycemic (i.e., in normal rats), antihyperglycemic as well as insulinotropic actions in alloxan-induced diabetic rats.