To investigate the regulatory effects of Angelica polysaccharides (AP) on proliferation,invasion and migration of vascular smooth muscle cells (VSMCs) stimulated by angiotensin Ⅱ (Ang Ⅱ) and heparin-binding epidermal growth factor (HB-EGF).Human vascular smooth muscle cells (hVSMCs) were pretreated with different concentrations of AP serum.Subsequently,Ang Ⅱ or HB-EGF was used to induce hVSMC proliferation and migration.The experiment was divided into the following groups:Blank control group,Ang Ⅱ (1 ng/mL) + control serum group,HB-EGF (1 ng/mL) + control serum group,Ang Ⅱ+AP serum group,HB-EGF+AP serum group,HB-EGF+AP serum group,Ang Ⅱ+AP+PI3K/AKT activator (IGF-1,10 μM) group and HB-EGF+AP serum+IGF-1 group.Cell proliferation was detected by CCK-8.Cell invasion and migration were tested by Transwell and Wound Healing assay,respectively.The expression levels of MMP2,MMP9,PI3K,p-PI3K,AKT,and p-AKT were detected by Western blot.The result showed that pretreatment with 100 mg/kg and 200 mg/kg AP serum had no cytotoxicity to VSMCs.Thus,100 mg/kg AP serum was used for subsequent experiments (A0).Ang Ⅱ or HB-EGF significantly stimulated the proliferation,invasion and migration of hVSMCs.Meanwhile,Ang Ⅱ or HB-EGF improved the expression levels of migration-related proteins MMP2 and MMP9.Of note,pretreatment of AP serum dramatically inhibited these processes.In addition,AP serum pretreatment reduced phosphorylation of PI3K and AKT in Ang Ⅱ or HB-EGF-induced hVSMCs.Co-treatment of IGF-1 reversed the inhibitory effect of AP serum on hVSMC proliferation,invasion and migration.In conclusion,AP serum can inhibit the proliferation and migration of hVSMCs induced by Ang Ⅱ or HB-EGF through inhibiting the activity of PI3K/AKT signaling pathways.