Pinocembrin protects the neurovascular unit by reducing inflammation and extracellular proteolysis in MCAO rats.
The purpose of the present study was to examine the protective action and mechanisms of pinocembrin (1) on the neurovascular unit (NVU) in permanent cerebral ischemic rats. Focal cerebral ischemia was induced by occlusion of middle cerebral artery (MCAO) in rats. Compound 1 (3, 10, or 30 mg/kg) was intravenously injected at 0, 8, 16 h after MCAO. At 24 h of occlusion, 1 alleviated neuronal apoptosis, edema of astrocytic end-feet, and the deformation of endothelial cells and capillaries as revealed by the transmission electron microscopy study. To understand the mechanisms of action, the anti-inflammation effect of 1 was examined. Compound 1 reduced the expressions of tumor necrosis factor-alpha, interleukin-1beta, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, inducible NO synthase and aquaporin-4; inhibited the activation of microglias and astrocytes; and downregulated the expression of matrix metalloproteinases (MMPs) in the ischemic brain. The ischemia-induced decreases in mRNA expressions of tight junction constituent proteins, occludin and ZO-1, were also inhibited by 1. These results indicated that 1 can protect the rat brain against ischemia injury by inhibiting the inflammatory cascade, reducing the expression of MMP-9, and preventing the integrity of tight junction. This resulted in the protective action of 1 on the NVU.
Gao
Mei
M
Peking Union Medical College, Institute of Materia Medica and Chinese Academy of Medical Sciences, Beijing, China.
Zhu
Shen-Yin
SY
Tan
Chu-Bing
CB
Xu
Bei
B
Zhang
Wen-Cui
WC
Du
Guan-Hua
GH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002545:Brain Ischemia / Q000139:chemically induced / Q000473:pathology*; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000139:chemically induced*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D053583:Interleukin-1beta / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects
D044950:Flavanones; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C016063:pinocembrin