Aqueous Extract of Opuntia ficus-indica (L. Mill) Cladodes Demonstrates Antidiabetic Effect in Normoglycemic and STZ-Induced Diabetic Rats

Abstract

Background: Opuntia ficus-indica (L. Mill) cladode is traditionally used for food and for the management of diabetes mellitus (DM), but its scientific basis and mechanisms remain underexplored.

Objective: The study assessed antidiabetic effects and mechanisms of action of O. ficus-indica aqueous extract (OFIAE).

Methods: Fresh cladodes were blended, centrifuged, and filtered to obtain OFIAE. Phytochemical profiling used colorimetric methods. Antidiabetic potential was evaluated via (1) oral glucose tolerance test (OGTT) in normoglycemic Sprague-Dawley rats pretreated with OFIAE (4, 40, and 400 mg/kg, p.o.), metformin, or none; (2) glucose uptake assay in yeast cells with glucose (5, 10, and 25 mM) ± OFIAE (125-1250 μg/mL); and (3) in vitro α-amylase and α-glucosidase inhibition. Experimental diabetes was induced in male Sprague-Dawley rats (STZ-nicotinamide; fasting blood glucose [FBG] > 11 mmol/L). Diabetic rats were treated orally for 28 days with OFIAE (4, 40, and 400 mg/kg), metformin (300 mg/kg), or vehicle. Body weight and FBG were recorded weekly. Glycated hemoglobin (HbA1c) was measured posttreatment. Liver (PAS and H&E) and pancreas (H&E and insulin immunostaining) were histologically examined.

Results: OFIAE contained flavonoids, alkaloids, and phenolic compounds. OFIAE significantly reduced postprandial blood glucose during OGTT compared to control. It enhanced glucose uptake in yeast and inhibited α-amylase (IC₅₀ = 411.1 ± 2.23 μg/mL) and α-glucosidase (IC₅₀ = 2486 ± 82.0 μg/mL). In diabetic rats, OFIAE reduced FBG and HbA1c levels while increasing body weight compared to the diabetic model. Liver sections showed increased glycogen storage (PAS staining). Pancreatic immunostaining revealed increased insulin expression in islet cells.

Conclusion: OFIAE exhibits antihyperglycemic effects by inhibiting carbohydrate-digestive enzymes (α-amylase and α-glucosidase), enhancing peripheral glucose uptake, increasing insulin secretion, and promoting hepatic glycogen storage. These findings validate its traditional use and highlight its potential as a complementary therapy for Type 2 DM.

Keywords: Opuntia ficus-indica; alpha amylase; alpha glucosidase; diabetes mellitus; hypoglycemia; insulin; streptozotocin.