Phellopterin isolated from Angelica dahurica reduces blood glucose level in diabetic mice

Insulin resistance is the critical condition for the development of metabolic syndromes including type II diabetes and heart disease. To investigate the active components of Angelica dahurica root which is known to increase insulin sensitivity, its methanol extract was subfractionated. The ethyl acetate (EtOAc) fraction of the Angelica dahurica root extract significantly promoted adipocyte differentiation in 3T3-L1 preadipocyte cells. Among the three compounds isolated from the EtOAc extract (bergapten (1), imperatorin (2) and phellopterin (3)), phellopterin (3) induced the highest adipocyte differentiation at 25 and 50 μg/mL. In addition, treatment with imperatorin (2) and phellopterin (3) increased the mRNA expression of peroxisome proliferator-activated receptors γ (PPARγ). In diabetic animal model induced by high-fat diets (HFD) and streptozotocin (STZ), administration of phellopterin ((3), 1 mg/kg and 2 mg/kg) significantly reduced the levels of blood glucose, triglycerides and total cholesterol. Taken together, these results indicate that phellopterin (3) enhances adipocytes differentiation in 3T3-L1 preadipocytes, phellopterin (3) significantly prevents HFD/STZ-induced type Ⅱ diabetes. The present study also provides phellopterin (3) may be a valuable therapeutic alternative for enhancing insulin sensitivity through promotion of adipocyte differentiation and by increasing mRNA expression levels of PPARγ, which is a major mediator of insulin sensitivity.