Therapeutic Potential of Pall. Root Extract As an Antidiabetic Agent: A Comprehensive Analysis from Molecular Mechanisms to In Vivo Efficacy

Pall. is widely used in traditional oriental herbal therapy, but its components and molecular mechanisms of action remain unclear. This study investigates the antidiabetic potential of Pall. root extract (RDR) and elucidates its underlying molecular mechanisms with in vitro and in vivo models. Data from the current study show that RDR exhibits strong antioxidant activity and glucose homeostasis regulatory effects. It significantly impacts glucose homeostasis in C2C12 skeletal muscle cells by inhibiting α-glucosidase activity. Further molecular mechanistic studies revealed that RDR promoted glucose uptake by phosphorylation of AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC), but not Phosphatidylinositol 3-kinase (PI 3-kinase)/Akt in C2C12 skeletal muscle cells. These actions increased the expression and translocation of glucose transporter type 4 (GLUT4) to the plasma membrane. In addition, RDR treatment in the STZ-induced diabetic rats remarkably improved the low body weight, polydipsia, polyphagia, hyperglycemia, and islet architecture and increased the insulin/glucose ratio. The liver (ALT and AST) and kidney marker enzyme (BUN and creatinine) levels were restored by RDR treatment as well. Phytochemical analysis identified eight major constituents in RDR, crucial for its antioxidant and antidiabetic activity. Through the molecular docking of representative glucose transporter GLUT4 with these compounds, it was confirmed that the components of RDR had a significantly high binding score in terms of structural binding. These findings from the current study highlight the antidiabetic effects of RDR. Collectively, our data suggest that RDR might be a potential pharmaceutical natural product for diabetic patients.