Effects of Non-Bitter Cucumis Metuliferus (Kiwano) Fruit Extract on the Metabolic Profiles of Streptozotocin-Induced Type II Diabetic Wistar Albino Rats

Abstract

Globally, about 400 million people have diabetes mellitus (DM), of whom the majority live in low- and middle-income countries. Every year, about 1.5 million deaths are directly attributed to diabetes mellitus and its associated complications. The cost of management of diabetes mellitus and its related complications is beyond reach to many people in low- and middle-income countries, necessitating the evaluation of locally available treatment alternatives. Although existing literature suggests that Cucumis metuliferus fruit possesses hypoglycaemic properties, empirical data to support this claim is scanty. The main objective of this study was to determine the effects of non-bitter Cucumis metuliferus fruit extract (CMFE) on the metabolic profiles of streptozotocin-induced type II diabetic Wistar Albino Rats. A total of 64 male Wistar albino rats weighing between 90 and 130 grams and aged 5 weeks were randomly assigned into two major groups, i.e., the control group and the experimental group. The control group received a standard rodent pellet diet plus 0.9% normal saline, whereas the experimental group received a high-fat/fructose diet plus streptozotocin (STZ) injection to induce diabetes mellitus. The experimental group was further divided into a positive control group, which was treated with pioglitazone (the standard drug) at a dose of 20 mg/kg body weight, a low-dose CMFE group (200 mg/kg body weight), and a high-dose CMFE group (400 mg/kg body weight). Fasting blood sugar (FBS), the oral glucose tolerance test (OGTT), and HbA1C were used as indicators of blood sugar. Serum HDL, LDL, total cholesterol, triglycerides, AST, ALT, GGT, ALP, total bilirubin, direct bilirubin, albumin, and total protein were used as indicators for liver functions. Body weight was recorded weekly, and at the endpoint of each group, the rats were fasted for 6–8 hours, anaesthetized with CO2, and fresh blood samples were collected through intra-cardiac puncture. "The ACCU CHEK" glucometer was used to test for FBS and OGTT, while the Clover A1C Self Hb A1C Analyser was used to test for Hb A1C. A CS T240 auto-chemistry analyser was used to test for liver functions. The pancreas was harvested for histological examination. The experiment ran for 70 days. The data was entered into a Microsoft Excel Spreadsheet and then transferred to SPSS version 25 for analysis. Comparison of multiple means was done using ANOVA, and Tukey's statistical test was used for Post hoc analysis. The analysis was done at a 95% level of confidence (P = 0.05). The data was presented using tables and figures. The study findings established that the extract contains glycosides, alkaloids, saponins, and tannins. An acute oral toxicity study revealed that at doses of 50 mg/kg, 300 mg/kg, and 2000 mg/kg body weight, the non-bitter CMFE is safe when administered to rats. This study established that treatment with a high-fat/fructose diet to induce type II DM significantly raised FBS (P <0.001) and OGTT (P <0.001), followed by a decrease to levels comparable to the control group after treatment with the non-bitter CMFE. Consequently, there was no significant difference (P >0.05) in Hb A1c test results, indicating that treatment with CMFE had a long-term control effect on blood sugar. Similarly, treatment with a high-fat/fructose diet significantly increased serum total cholesterol (TC) (P <0.001), triglycerides (TGs) (P = 0.019), and low-density lipoproteins (LDL) (P = 0.016), followed by a decrease to levels comparable to the control group after treatment with the non-bitter CMFE. On the contrary, treatment with a high-fat/fructose diet significantly decreased (P =0.004) serum high-density lipoproteins (HDL), which was followed by a significant increase (P =0.001) after treatment with non-bitter CMFE. The findings also established that treatment with streptozotocin to induce type II DM significantly increased serum alanine aminotransferase (ALT) (P <0.001), aspartate aminotransferase (AST) (P <0.001), and gamma-glutamyl transferase (GGT) (P =0.002), followed by a decrease to levels comparable to the control group after treatment with the non-bitter CMFE. Notably, treatment with streptozotocin (STZ) to induce type 2 DM markedly reduced cell density in the Islet of Langerhans, indicative of STZ-induced beta cell dysfunction. However, treatment with CMFE increased the number of metabolically active cells in the Islet of Langerhans. In conclusion, this study demonstrates that CMFE has hypoglycaemic, hypolipidemic, and hepato-restorative properties. The study recommends the use of the non-bitter Cucumis metuliferus fruit extract as an adjunct in the control of blood sugar in type II DM. The study also recommends the use of the non-bitter Cucumis metuliferus fruit extract in the management of diabetic and nutritionally induced dyslipidemias.