AQUEOUS

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.