Protective and Antidiabetic Effects of Polygonum plebeium R.Br. in STZ-Induced Diabetic Rats

Polygonum plebeium R. Br. (Polygonaceae), commonly known as small knotweed, is traditionally used in South Asia to treat intestinal disorders, pneumonia, and menstrual ailments. The present study systematically evaluated its antidiabetic potential through integrated phytochemical, in vitro, in vivo, and in silico approaches. Aerial parts were sequentially extracted using solvents of increasing polarity, and the ethanol extract was analyzed by GC–MS, identifying 11 phytoconstituents. Oleic acid (24.06%) and pentadecanoic acid ethyl ester (21.99%) were major compounds. In vitro antidiabetic activity demonstrated significant enzyme inhibition, with IC₅₀ values of 95.06 ± 0.35 µg/ml for α-amylase and 90.32 ± 0.64 µg/ml for α-glucosidase. In vivo studies included oral glucose tolerance test (OGTT), acute and chronic antihyperglycemic evaluations, and streptozotocin-induced diabetic rat models. At 400 mg/kg, the extract reduced blood glucose by 30.52% after 3 h in OGTT. Acute treatment produced a 55.74 ± 3.47% reduction at 8 h, while 30-day administration resulted in a 59.79 ± 1.07% decrease. Significant improvements were observed in liver enzymes, HbA1c, total protein, and lipid profile. Histopathological analysis revealed regeneration of pancreatic islets and restoration of liver and kidney architecture. Molecular docking studies against α-amylase, α-glucosidase, PPAR-γ, and GLUT-2 showed strong binding affinity of stevioside with key targets, supporting the experimental findings. In conclusion, highlight the promising antidiabetic potential of P. plebeium and justify further investigation for therapeutic development.