PMID- 20496198 OWN - NLM STAT- MEDLINE DCOM- 20100611 LR - 20171116 IS - 1477-2213 (Electronic) IS - 1028-6020 (Linking) VI - 12 IP - 5 DP - 2010 May TI - Pinocembrin protects the neurovascular unit by reducing inflammation and extracellular proteolysis in MCAO rats. PG - 407-18 LID - 10.1080/10286020.2010.485129 [doi] AB - 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. FAU - Gao, Mei AU - Gao M AD - Peking Union Medical College, Institute of Materia Medica and Chinese Academy of Medical Sciences, Beijing, China. FAU - Zhu, Shen-Yin AU - Zhu SY FAU - Tan, Chu-Bing AU - Tan CB FAU - Xu, Bei AU - Xu B FAU - Zhang, Wen-Cui AU - Zhang WC FAU - Du, Guan-Hua AU - Du GH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Asian Nat Prod Res JT - Journal of Asian natural products research JID - 100888334 RN - 0 (Flavanones) RN - 0 (Interleukin-1beta) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 8T7C8CH791 (pinocembrin) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Brain/drug effects MH - Brain Ischemia/chemically induced/*pathology MH - Flavanones/pharmacology/*therapeutic use MH - Infarction, Middle Cerebral Artery/*chemically induced MH - Inflammation/chemically induced/*drug therapy MH - Intercellular Adhesion Molecule-1/drug effects MH - Interleukin-1beta/drug effects MH - RNA, Messenger/drug effects MH - Rats MH - Tumor Necrosis Factor-alpha/drug effects MH - Vascular Cell Adhesion Molecule-1/drug effects EDAT- 2010/05/25 06:00 MHDA- 2010/06/12 06:00 CRDT- 2010/05/25 06:00 PHST- 2010/05/25 06:00 [entrez] PHST- 2010/05/25 06:00 [pubmed] PHST- 2010/06/12 06:00 [medline] AID - 922439826 [pii] AID - 10.1080/10286020.2010.485129 [doi] PST - ppublish SO - J Asian Nat Prod Res. 2010 May;12(5):407-18. doi: 10.1080/10286020.2010.485129.