Cornin increases angiogenesis and improves functional recovery after stroke via the Ang1/Tie2 axis and the Wnt/β-catenin pathway.
We investigated whether cornin, an iridoid glycoside isolated from fruits of Verbena officinalis L., regulated angiogenesis and thereby improved functional outcomes after stroke and discovered a potential mechanism. The effects of cornin on proliferation of rat artery smooth muscle cell (RASMC) and signalling was investigated in vitro. Adult male rats were subjected to 1 h of middle cerebral artery occlusion (MCAO) and reperfusion and treated with or without 25 mg/kg of cornin, starting 24 h after ischemia and reperfusion, by continuous intravenous injection daily for 14 days. Neurological functional tests were performed and cerebral Evans blue extravasation was measured. Angiogenesis and angiogenic factor expressions were measured by immunohistochemistry and Western blotting, respectively. Cornin increased the proliferation of RASMC and enhanced the expression of Wnt5a, β-catenin, cyclin D1 and angiopoietin-1 (Ang1). Cornin treatment promoted angiogenesis in the ischemic brain core and improved functional outcomes after stroke. Cornin-treated MCAO rats showed significant increase in vascularization and expression of vascular endothelial growth factor and Ang1 and phosphorylation of Tie2 and Akt compared with vehicle-treated MCAO rats. The Ang1/Tie2 axis and Wnt/β-catenin pathways appear to mediate cornin-induced angiogenesis.
School of Pharmaceutical Sciences, Binzhou Medical University, No 346, Guanhai Road, Laishan District, Yantai, 264003, People's Republic of China.
Yangyang
Y
Xu
School of Pharmaceutical Sciences, Binzhou Medical University, No 346, Guanhai Road, Laishan District, Yantai, 264003, People's Republic of China.
Guanghua
G
Zhang
School of Pharmaceutical Sciences, Binzhou Medical University, No 346, Guanhai Road, Laishan District, Yantai, 264003, People's Republic of China.
Zechun
Z
Kang
School of Pharmaceutical Sciences, Binzhou Medical University, No 346, Guanhai Road, Laishan District, Yantai, 264003, People's Republic of China.
Yong
Y
Xu
School of Pharmaceutical Sciences, Binzhou Medical University, No 346, Guanhai Road, Laishan District, Yantai, 264003, People's Republic of China. jwl518@163.com.
Wangling
W
Jiang
School of Pharmaceutical Sciences, Binzhou Medical University, No 346, Guanhai Road, Laishan District, Yantai, 264003, People's Republic of China. zsp1963yt@163.com.
Shuping
S
Zhang
D042683:Angiopoietin-1 / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D057889:Iridoid Glycosides / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism*; D032412:Verbena; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism*
D042683:Angiopoietin-1; D057889:Iridoid Glycosides; D010936:Plant Extracts; D051176:beta Catenin; C000511:cornin iridoid; D042787:Receptor, TIE-2
Ang1/Tie2; Angiogenesis; Cornin; VEGF; Wnt/β-catenin