Concomitant Down Regulation of Glycolytic Enzymes, Upregulation of Gluconeogenic Enzymes and Potential Hepato-Nephro-Protective Effects Following the Chronic Administration of the Hypoglycemic, Insulinotropic Citrullus colocynthis Pulp Extract

Background Citrullus colocynthis pulp seedless extract has been demonstrated to have antihyperglycemic and insulinotropic effects. Problem statement: The mechanism(s) underlying the antihyperglycemic and insulinotropic effects have not been investigated to date. Approach: The influence of Citrullus colocynthis pulp extract administered orally was studied in alloxan diabetic white albino rats. Rats were divided into four groups, the first group was normal non diabetic rats given normal saline orally and was named control group, the second group was diabetic rats given normal saline orally and were named normal saline treated-diabetic rats, the third and fourth group were diabetic rats treated with the pulp extract or glybenclamide (a positive control) orally. Plasma glucose, glycosylated hemoglobin and insulin were determined in all groups. The effect of pulp extract of this plant on liver and kidney tissues was also studied. The amount of insulin in β-cells of the Islets of Langerhans in all groups was assessed using immunohistochemistry procedure. Results: Treatment of diabetic rats with Citrullus colocynthis pulp extract (300 mg kg^-1 body weight) resulted in a significant decrease in plasma glucose, glygosylated Hb and increased insulin levels. This significant increase in insulin may explain the increase in the activity of liver hexokinase, with concomitant decrease of glucose 6-phosphatase and fructose-1,6-bisphosphatase. Immunohistochemistry procedure showed that the amount of insulin in β-cells of the islets of Langerhans is greater in Citrullus colocynthis treated-diabetic rats in comparison to non-treated diabetic rats. Conclusion: The present study clearly demonstrated that the folk medicinal plant Citrullus colocynthis pulp extract possesses a hypoglycemic effect, through an increase in insulin production and the subsequent increase in activity of glycolytic enzyme and decrease in activity of enzymes of gluconeogenesis. The present study also showed that the pulp extract of this plant to may have protective effects on the liver and kidney.