Tadehaginosides A-J, Phenylpropanoid Glucosides from Tadehagi triquetrum, Enhance Glucose Uptake via the Upregulation of PPARγ and GLUT-4 in C2C12 Myotubes

Ten new phenylpropanoid glucosides, tadehaginosides A-J (1-10), and the known compound tadehaginoside (11) were obtained from Tadehagi triquetrum. These phenylpropanoid glucosides were structurally characterized through extensive physical and chemical analyses. Compounds 1 and 2 represent the first set of dimeric derivatives of tadehaginoside with an unusual bicyclo[2.2.2]octene skeleton, whereas compounds 3 and 4 contain a unique cyclobutane basic core in their carbon scaffolds. The effects of these compounds on glucose uptake in C2C12 myotubes were evaluated. Compounds 3-11, particularly 4, significantly increased the basal and insulin-elicited glucose uptake. The results from molecular docking, luciferase analyses, and ELISA indicated that the increased glucose uptake may be due to increases in Peroxisome Proliferator-activated Receptor γ (PPARγ) activity and glucose transporter-4 (GLUT-4) expression. These results indicate that the isolated phenylpropanoid glucosides, particularly compound 4, have the potential to be developed into antidiabetic compounds.