We investigated whether 8-O-acetyl shanzhiside methylester (ND01) regulates angiogenesis and thereby improves functional outcome after stroke. Adult male rats were subjected to 1 hr of middle cerebral artery occlusion (MCAO) and reperfusion, and treated with or without different doses (5 and 10 mg/kg) of ND01, starting 24 hr after ischaemia and reperfusion (I/R) and by intravenous injection daily for 14 days. Neurological functional tests were performed and cerebral Evans blue extravasation was measured. Angiogenesis and angiogenic factor expression were measured by immunohistochemistry and Western blot, respectively. The results indicated that ND01 significantly promoted angiogenesis in the ischaemic brain and improved functional outcome after stroke. ND01 also significantly increased vascularization compared with vehicle treatment. ND01 increased the expression of VEGF, Ang1, phosphorylation of Tie2 and Akt VEGF. The Ang1/Tie2 axis and Akt pathways appear to mediate ND01-induced angiogenesis.
© 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.