STREPTOZOTOCIN-INDUCED

Diabetes mellitus (DM), a metabolic disease characterized by chronic hyperglycemia causes damage to important tissues and organs (heart, liver, blood vessels, kidneys and nerves). The aim of this study was to evaluate the effect of ethanol extract of Chrysophyllum albidum stem bark and its fractions on some biochemical status in streptozotocin (STZ)-induced diabetic rats. Crude ethanol extract prepared from pulverised stem bark of the plant was fractionated using analytical grade solvents (n-hexane, ethylacetate, and methanol). Adult male rats (Wistar strain, n = 56) weighing between 150 and 200 g were randomly assigned to eight groups (7 rats/group): control, diabetic, metformin, extract, and hydroethanol, n-hexane, ethyl acetate and methanol fractions. With the exception of control group, DM was induced in the rats via intraperitoneal injection of STZ (50 mg/kg body weight). This was followed by treatment (daily) with either metformin, ethanol extract or fractions of C. albidum stem bark for 14 days. At the expiration of the treatment period, plasma/tissue samples obtained from the rats were used for biochemical analyses. Blood glucose concentration and body weight were monitored on weekly basis. Indices of liver and kidney function; oxidative status in selected tissues (plasma, liver, kidney, pancreas), lipid peroxidation index and haematological parameters were measured. The results obtained showed that induction of DM with STZ significantly increased fasting blood glucose (FBG) level, organ weights (liver, kidney), malondialdehyde (MDA), indices of liver and kidney function, lipid profile, and some haematological parameters (white blood cell, lymphocyte, granulocyte, mid-cell), but it decreased the activities/levels of hepatic/renal/pancreatic antioxidant enzymes [catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx)], body weight, pancreas weight, plasma total protein, albumin, and electrolytes (Na⁺, K⁺, HCO₃⁻), high-density lipoprotein holesterol (HDL-C), platelet count, and red blood cell indices when compared to control (p < 0.05). However, treatment with C. albidum stem bark extract/fractions markedly reduced FBG level, organ weights (liver, kidney), and MDA, but it enhanced the activities of the antioxidant enzymes and pancreas weight (p < 0.05). Similarly, extract/fractions treatment improved lipid profile and haematological parameters, while restoring indices of liver and kidney function. The results were comparable to those of metformin (standard drug). Histopathological examination of pancreatic and liver tissues of diabetic untreated rats showed cell reduction of the islet of Langerhans and pancreatic acini, congestion of the central vein, as well as loss of normal hepatocytic architecture, indicating severe pancreatic and liver damage. However, treatment with C. albidum extract/fractions revealed improvement in liver/pancreas histology. Histopathological examination of pancreatic and liver tissues further supported the biochemical findings. The results obtained in this study have shown that ethanol extract of C. albidum stem bark and its fractions can markedly reduce typical derangements associated with STZ-induced diabetes mellitus (that is, hyperglycaemia, hyperlipidemia, hepatotoxicity, nephrotoxicity, and oxidative stress.

Diabetes mellitus is a metabolic disorder marked by persistent hyperglycemia, which drives yet often overlooked aspect of diabetes pathophysiology is its reciprocal relationship with physiological stress. Oxidative stress can impair the function of the Hypothalamic–Pituitary– Adrenal (HPA) axis, causing an increase in cortisol secretion. Elevated cortisol, in turn, aggravates hyperglycemia and intensifies oxidative damage, creating a vicious cycle that accelerates the onset and progression of diabetic complications. Picralima nitida, a medicinal plant traditionally used in diabetes treatment, is known for its antidiabetic and antioxidant properties. However, its potential role in modulating cortisol imbalances associated with diabetes has not been previously examined. This study therefore investigated the protective effects of an aqueous fruit extract of Picralima nitida (APN) on hyperglycemia, oxidative stress, and serum cortisol levels in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in adult male Wistar rats using STZ (55 mg/kg), after which the animals received varying doses of APN for a specified treatment period. A group treated with glibenclamide served as the standard drug control. Fasting blood glucose levels were monitored throughout the study, and serum cortisol concentrations were measured using a competitive ELISA technique. The findings revealed that STZ-induced diabetic rats experienced a significant rise in cortisol levels (18.5 ± 0.1 µg/ml) compared with the non-diabetic control group (13.35 ± 2.45 µg/ml), confirming that oxidative stress triggers heightened HPA axis activity. Treatment with APN produced a pronounced reduction in cortisol levels, with the low-dose and high-dose groups showing values of 10.3 ± 1.4 µg/ml and 10.15 ± 1.45 µg/ml respectively. These reductions were statistically significant when compared with both the control and diabetic groups (P < 0.05). In addition, APN administration led to marked improvements in fasting blood glucose and oxidative stress markers. In summary, the study demonstrates that Picralima nitida effectively lowers blood glucose, mitigates oxidative stress, and corrects cortisol imbalances in diabetic rats. These results underscore its potential therapeutic value in addressing both metabolic disturbances and stress-related abnormalities associated with diabetes mellitus.