Effects of butanol fraction of Ziziphus mucronata root ethanol extract on glucose homeostasis, serum insulin and other diabetes-related parameters in a murine model for type 2 diabetes

Abstract

Context: Ziziphus mucronata Willd (Rhamnaceae) is currently used in Nigerian traditional treatment of diabetes mellitus. However, detailed information on the antidiabetic potential of the plant parts is presently unknown.

Objectives: The present study investigated the antidiabetic effects of the butanol fraction of Z. mucronata root (ZMBF) in a type 2 diabetes (T2D) model of rats.

Materials and methods: T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by an intraperitoneal injection of streptozotocin (40 mg/kg bw) and the animals were orally treated with ZMBF 150 or 300 mg/kg bw for five days a week for four weeks. Food and fluid intake, body weight changes and blood glucose levels were monitored during the experiment while other blood and organ specific diabetes-associated parameters were measured at the end of the experiment.

Results: After four-week treatment, significantly (p < 0.05) lower blood glucose (19.24 vs 28.96 mmol/L), improved glucose tolerance ability (21.26 vs 28.56 mmol/L), higher serum insulin (131.37 vs 64.20 pmol/L) and liver glycogen (2.40 vs 1.54 mg/g tissue) were observed in the 300 mg/kg ZMBF ingested group compared with the diabetic control group. However, food and fluid intake, body weight gain, HOMA-β, HOMA-IR, serum fructosamine level, hepatic and renal function tests were not significantly (p > 0.05) affected by the treatment of ZMBF.

Conclusion: Results of this study suggest that ZMBF treatment, at 300 mg/kg bw, possess antidiabetic activity, but could not ameliorate some diabetes-related parameters in type 2 diabetic rats.

Keywords: Buffalo thorn; blood glucose; glucose tolerance; insulin resistance; liver glycogen; β-cell function.

Figure 1.

The effects of oral treatment of butanol fraction of Z. mucronata root on feed and fluid intakes of type 2 diabetic rats. Data are presented as the mean ± SD of eight animals. ^a–bValues with different letters over the bars for a given parameter are significantly different from each other (Tukey’s-HSD multiple range post hoc test, p < 0.05). NC: Normal Control; DBC: Diabetic Control; DZL: Diabetic Ziziphus mucronata low dose (150 mg/kg bw); DZH: Diabetic Ziziphus mucronata high dose (300 mg/kg bw); DMF: Diabetic metformin; NZT: Normal Ziziphus mucronata toxicological dose (300 mg/kg bw).

Figure 2.

The effects of oral treatment of butanol fraction of Z. mucronata root on mean body weight gain of type 2 diabetic rats. Data are presented as the mean ± SD of eight animals. ^a–bValues with different letters for a given week are significantly different from each other (Tukey’s-HSD multiple range post hoc test, p < 0.05). NC: Normal Control; DBC: Diabetic Control; DZL: Diabetic Ziziphus mucronata low dose (150 mg/kg bw); DZH: Diabetic Ziziphus mucronata high dose (300 mg/kg bw); DMF: Diabetic metformin; NZT: Normal Ziziphus mucronata toxicological dose (300 mg/kg bw).

Figure 3.

Weekly blood glucose concentrations (post induction) of different animal groups. Data are presented as the mean ± SD of eight animals. ^a–dValues with different letters for a given week are significantly different from each other (Tukey’s-HSD multiple range post hoc test, p < 0.05). NC: Normal Control; DBC: Diabetic Control; DZL: Diabetic Ziziphus mucronata low dose (150 mg/kg bw); DZH: Diabetic Ziziphus mucronata high dose (300 mg/kg bw); DMF: Diabetic metformin; NZT: Normal Ziziphus mucronata toxicological dose (300 mg/kg bw).

Figure 4.

Oral glucose tolerance test (OGTT) for all groups of animals in the last week of experimental period. Data are presented as the mean ± SD of eight animals. ^a–cValues with different letters for a given time are significantly different from each other (Tukey’s-HSD multiple range post hoc test, p < 0.05). NC: Normal Control; DBC: Diabetic Control; DZL: Diabetic Ziziphus mucronata low dose (150 mg/kg bw); DZH: Diabetic Ziziphus mucronata high dose (300 mg/kg bw); DMF: Diabetic metformin; NZT: Normal Ziziphus mucronata toxicological dose (300 mg/kg bw).

Figure 5.

Representative sections of histopathological examinations of the pancreas from different animal groups. The NC group had higher number of cells per islet while the DBC and DZL group had smaller pancreatic islets with very few cells. The DZH had relatively higher number of cells per islet compared to DBC and DZL groups but far lower than the NC group. NC: Normal Control; DBC: Diabetic Control; DZL: Diabetic Ziziphus mucronata low dose (150 mg/kg bw); DZH: Diabetic Ziziphus mucronata high dose (300 mg/kg bw); DMF: Diabetic metformin; NZT: Normal Ziziphus mucronata toxicological dose (300 mg/kg bw).