title: 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-Glucoside Attenuates Ischemia/Reperfusion-Induced Brain Injury in Rats by Promoting Angiogenesis.
abstract: Cerebral ischemia can cause brain infarcts, which are difficult to recover due to poor angiogenesis. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside is a natural polyphenol, has antioxidant and anti-inflammatory activity, and can protect from ischemic neuronal injury. However, little is known about the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside on brain microcirculation after stroke. This study aimed at investigating the influence of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside on brain lesions and angiogenesis after stroke. Sprague-Dawley rats were subjected to right middle cerebral artery occlusion and treated with vehicle, nimodipine, or different doses of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside daily beginning at 6 h post-middle cerebral artery occlusion for 14 days. The volume of cerebral infarcts, degree of neurological dysfunction, and level of microvessel density were determined longitudinally. The levels of vascular endothelial growth factor, angiopoietin 1, and angiopoietin receptor-2 expression in the brain lesions were characterized by immunohistochemistry and Western blot assays at 14 days post-middle cerebral artery occlusion. We found that 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside significantly promoted postoperative recovery in rats by minimizing the volume of cerebral infarcts and improving neurological dysfunction in a dose- and time-dependent manner. Additionally, 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside significantly increased the microvessel density in the brain and upregulated CD31 expression in ischemic penumbra, relative to that in the control. Finally, treatment with 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside significantly upregulated the relative levels of vascular endothelial growth factor, angiopoietin 1, and angiopoietin receptor-2 expression in the brain lesions of rats. Therefore, these data indicated that 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside treatment promoted angiogenesis and recovery from ischemia/reperfusion-induced brain injury in rats.
authors.affiliation: Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mu
authors.affiliation: 323th Hospital of PLA, Xian, People's Republic of China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, People's Republic of China.
authors.forename: Xuanxuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xian, People's Republic of China.
authors.forename: Huinan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, People's Republic of China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, People's Republic of China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xian, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xian, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, People's Republic of China.
authors.forename: Siwang
authors.initials: S
authors.lastname: Wang
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use*; D000803:Angiotensin I / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000517:prevention & control*; D002545:Brain Ischemia; D000068676:Fallopia multiflora / Q000737:chemistry; D005960:Glucosides / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy*; D013267:Stilbenes / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D005960:Glucosides; D018696:Neuroprotective Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; D000803:Angiotensin I; D042787:Receptor, TIE-2