Hydrangeic acid from the processed leaves of Hydrangea macrophylla var. thunbergii as a new type of anti-diabetic compound

Hydrangeic acid (3–100 μM), a stilbene constituent of the processed leaves of Hydrangea macrophylla var. thunbergii (Hydrangeae Dulcis Folium), promoted adipogenesis of 3T3-L1 cells. Hydrangeic acid significantly increased the amount of adiponectin released into the medium, the uptake of 2-deoxyglucose into the cells, and the translocation of glucose transporter 4 (GLUT4). Hydrangeic acid also increased mRNA levels of adiponectin, peroxisome proliferator-activated receptor γ2 (PPARγ2), GLUT4, and fatty acid-binding protein (aP2) while it decreased the expression of tumor necrosis factor α (TNF-α) mRNA. However, it did not activate PPARγ directly different from troglitazone in a nuclear receptor cofactor assay system. Furthermore, hydrangeic acid significantly lowered blood glucose, triglyceride, and free fatty acid levels after its administration for 2 weeks at a dose of 200 mg/kg/day (p.o.) in KK-Ay mice.