Dose Dependent Dual Effect of Baicalin and Herb Huang Qin Extract on Angiogenesis

Huang Qin (root of Scutellaria baicalensis) is a widely used herb in different countries for adjuvant therapy of inflammation, diabetes, hypertension, different kinds of cancer and virus related diseases. Baicalin is the main flavonoid in this herb and has been extensively studied for 30 years. The angiogenic effect of herb Huang Qin extract and baicalin was found 13 years ago, however, the results were controversial with pro-angiogenic effect in some studies and anti-angiogenic effect in others. In this paper, the angiogenic effect of baicalin, its aglycone form baicalein and aqueous extract of Huang Qin was studied in chick embryo chorioallantoic membrane (CAM) model. Dose dependent dual effect was found in both aqueous extract and baicalin, but not in baicalein, in which only inhibitory effect was observed. In order to reveal the cellular and molecular mechanism of how baicalin and baicalein affect angiogenesis, cell proliferation and programmed cell death assays were performed in treated CAM. In addition, quantitative PCR array including 84 angiogenesis related genes was used to detect high and low dosage of baicalin and baicalein responsive genes. Low dose baicalin increased cell proliferation in developing blood vessels through upregulation of multiple angiogenic genes expression, but high dose baicalin induced cell death, performing inhibitory effect on angiogenesis. Both high and low dose of baicalein down regulated the expression of multiple angiogenic genes, decreased cell proliferation, and leads to inhibitory effects on angiogenesis.