2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-Glucoside Attenuates Ischemia/Reperfusion-Induced Brain Injury in Rats by Promoting Angiogenesis

Ying Mu; Zhaohui Xu; Xuanxuan Zhou; Huinan Zhang; Qian Yang; Yunlong Zhang; Yanhua Xie; Juan Kang; Feng Li; Siwang Wang

doi:10.1055/s-0042-120544

Planta Medica, Table of Contents

Planta Med 2017; 83(08): 676-683
DOI: 10.1055/s-0042-120544

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-Glucoside Attenuates Ischemia/Reperfusion-Induced Brain Injury in Rats by Promoting Angiogenesis

Ying Mu^*

¹Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, Peopleʼs Republic of China

²Collaborative Innovation Center for Chinese Medicine in Qinba Mountain, Xian, Peopleʼs Republic of China

,

Zhaohui Xu^*

³323th Hospital of PLA, Xian, Peopleʼs Republic of China

,

Xuanxuan Zhou

¹Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, Peopleʼs Republic of China

²Collaborative Innovation Center for Chinese Medicine in Qinba Mountain, Xian, Peopleʼs Republic of China

,

Huinan Zhang

⁵Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xian, Peopleʼs Republic of China

,

Qian Yang

¹Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, Peopleʼs Republic of China

²Collaborative Innovation Center for Chinese Medicine in Qinba Mountain, Xian, Peopleʼs Republic of China

,

Yunlong Zhang

¹Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, Peopleʼs Republic of China

²Collaborative Innovation Center for Chinese Medicine in Qinba Mountain, Xian, Peopleʼs Republic of China

,

Yanhua Xie

¹Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, Peopleʼs Republic of China

²Collaborative Innovation Center for Chinese Medicine in Qinba Mountain, Xian, Peopleʼs Republic of China

,

Juan Kang

⁶Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xian, China

,

Feng Li

⁴Department of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xian, China

,

Siwang Wang

¹Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, Peopleʼs Republic of China

²Collaborative Innovation Center for Chinese Medicine in Qinba Mountain, Xian, Peopleʼs Republic of China

› Author Affiliations

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.

Key words

Polygonum multiflorum - Polygonaceae - 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside - cerebral ischemia/reperfusion - angiogenesis

Full Text

References

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