Antidiabetic and Antioxidant Properties of Cnidoscolus aconitifolius Leaf Extract: Biochemical Mechanisms in Streptozotocin-Induced Diabetic Rats

Cnidoscolus aconitifolius (chaya or tree spinach) is consumed as a leafy vegetable in parts of southwestern Nigeria and has been attributed with antidiabetic properties in local ethnobotanical knowledge, but the biochemical mechanisms underlying these properties have not been systematically investigated. This study elucidates the antidiabetic and antioxidant mechanisms of methanol leaf extract of Cnidoscolus aconitifolius in streptozotocin-induced diabetic rats. Phytochemical characterisation was performed by GC-MS and HPLC to identify bioactive constituents. Forty-eight Wistar rats were divided into eight groups including normal controls, diabetic controls, metformin reference, and five extract treatment groups at doses from 100 to 500 mg/kg. Diabetes was induced by intraperitoneal streptozotocin injection. Treatment was administered for four weeks. Biochemical assessments covered fasting and postprandial glucose, serum insulin, HbA1c, glucokinase and glucose-6-phosphatase activities in liver homogenate, hexokinase activity, pancreatic beta-cell histology by immunohistochemistry for insulin, and a comprehensive oxidative stress panel in liver and kidney tissues. GC-MS analysis identified quercetin, rutin, kaempferol, and beta-sitosterol as major phytoconstituents. The 400 and 500 mg/kg doses significantly reduced fasting and postprandial glucose, normalized HbA1c, and elevated serum insulin to near-normal levels. Mechanistic analysis showed significant inhibition of glucose-6-phosphatase and stimulation of glucokinase and hexokinase, favouring glucose uptake and glycolysis over gluconeogenesis. Oxidative stress markers were significantly normalized in both liver and kidney tissues. Immunohistochemistry showed preserved insulin-positive beta-cell mass in treated rats. Keywords: Cnidoscolus aconitifolius, antidiabetic mechanisms, streptozotocin, glucokinase, oxidative stress.