Cathinone: An alkaloid of Catha edulis (Khat) exacerbated hyperglycemia in diabetes-induced rats

Abstract

Cathinone, the main bioactive alkaloid of Catha edulis (khat), slightly increased the blood sugar levels of healthy animals, while its effect on blood sugar levels of diabetic animals has not yet been reported. This study investigated the in vitro inhibition of cathinone on α-amylase and α-glucosidase as well as its in vivo glycemic effects in diabetes-induced rats. Rats were fed on a high fat diet for five weeks, which then intraperitoneally injected with streptozotocin (30 mg/kg). Diabetic rats were distributed randomly into diabetic control (DC, n = 5), 10 mg/kg glibenclamide-treated group (DG, n = 5), and 1.6 mg/kg cathinone-treated group (CAD, n = 5). Additional healthy untreated rats (n = 5) served as a nondiabetic negative control group. Throughout the experiment, fasting blood sugar (FBS), caloric intake and body weight were recorded weekly. By the 28th day of treatment, rats were euthanized to obtain blood samples and pancreases. The results demonstrated that cathinone exerted a significantly less potent in vitro inhibition than α-acarbose against α-amylase and α-glucosidase. As compared to diabetic control group, cathinone significantly increased FBS of diabetic rats, while insulin levels of diabetic rats significantly decreased. In conclusion, cathinone was unable to induce a substantial in vitro inhibition on α-amylase and α-glucosidase, while it exacerbated the hyperglycemia of diabetes-induced rats.

Keywords: Catha edulis; Cathinone; Diabetes mellitus; Khat; α-Amylase; α-Glucosidase.

Fig. 1

Histopathological changes in pancreatic sections. Black arrows point to vacuolated areas. Red arrows point to β-cells, AC, Acinar cells; IL, the islet of Langerhans; NC, nondiabetic control group; DC, diabetic control group; DG, glibenclamide-treated diabetic group; CAD, cathinone-treated diabetic group. H&E stain; 100×.

Fig. 2

Morphometric evaluation of the pancreatic sections, (a) The size distribution of islets of Langerhans per 50 microscopic field was expressed as area in µm². ^##P ≤ 0.01, area of islets of the DC group was significantly smaller than that of NC group. *P ≤ 0.05, the area of the GD group was significantly larger than that of DC group, while that of CAD group was smaller than DC group; (b) Number of islets of Langerhans per 50 microscopic fields was counted using 40× magnification. The density volume of islets of Langerhans was expressed as a percentage of islets per 50 microscopic fields. ^###P ≤ 0.001, the number and density volume of islets of Langerhans of the DC group were significantly smaller than that of NC group; (c) Number of β- and α-cells per 10 islets was counted using 100× magnification. The density volume of β-cells per 10 islets of Langerhans was expressed as a percentage of β-cells to the total number of α- and β-cells. ^###P ≤ 0.001, the number of β-cells, the number of α-cells and the density volume of β-cells of the DC group was significantly greater than that of NC group; * P ≤ 0.05, the number of α-cells of GD and CAD groups were significantly greater than that of DC group. Data are graphically presented as the mean ± SE. NC, nondiabetic control group; DC, diabetic control group; DG, glibenclamide-treated diabetic group; CAD, cathinone-treated diabetic group.

Fig. 3

Immunofluorescence of insulin, glucagon and insulin to glucagon ratio, (A): Double immunofluorescence labeling using glucagon (green) and insulin (red) in pancreatic sections (scale bar = 100 µm), (B): Percentage of insulin positive cells, (C): Percentage of glucagon positive cells, (D): Insulin to glucagon ratio. ^###P ≤ 0.001 vs. NC group, while *P ≤ 0.001 and ^***P ≤ 0.05 vs. DC group. NC: nondiabetic control, GD: glibenclamide-treated diabetic group, CAD: cathinone-treated diabetic rats.