Abstract

Diabetes mellitus, a condition characterized by hyperglycemia, poses significant global health concern. Despite the availability of several antidiabetic drugs, the search for new therapeutic agents with fewer side effects and better efficacy continues. Phanera strychnifolia (Craib) K. W. Jiang, S. R. Gu, & T. Y. Tu, a medicinal plant traditionally used in Southeast Asia, has gained attention for its bioactive components. Two major compounds isolated, namely, 3,5,7-trihydroxychromone-3-O-α-L-rhamnopyranoside and 3,5,7,3′,5′-pentahydroxy-flavanonol-3-O-α-L-rhamnopyranoside, have shown promise as antihyperglycemic agents in human intestinal epithelial Caco-2 cells. It had been demonstrating antidiabetic and antioxidant activities of its aqueous extract in both in vivo and in vitro studies with limited information regarding their antihyperglycemic effect on insulin secretion and glucose transporter expression. Therefore, this study aims to evaluate the impact of P. strychnifolia extracts on blood glucose levels in diabetic rats and to investigate the expression of glucose transporter proteins (GLUT2 and GLUT4) and insulin production in relevant tissues to elucidate the mechanisms of improved glucose uptake and utilization. The antidiabetic effect of P. strychnifolia was determined by histological staining and immunocytochemical localization of insulin, GLUT2, and GLUT4 in pancreatic islets and the heart. Additionally, toxicity assessment was conducted over a 63-day administration by observing biochemical parameters and histological changes. P. strychnifolia demonstrates nontoxic characteristics, as evidenced by the absence of mortality and clinical toxicity signs at the 400 mg/kg dose after 63 days of treatment. In diabetic rats, administration of 100 and 200 mg/kg of P. strychnifolia for 14 days significantly reduced blood glucose levels by approximately 45.65% and 41.01%, respectively, compared to the diabetic control group. Both doses effectively reduced lipid droplets in the liver, indicating decreased tissue injury. P. strychnifolia demonstrates significant antihyperglycemic activity and beneficial effects on insulin and glucose transporter protein expression in diabetic rats, with no observed toxicity. These findings suggest its potential as a therapeutic agent for diabetes management.