title: Huanglian-Jie-Du-Tang extract protects against chronic brain injury after focal cerebral ischemia via hypoxia-inducible-factor-1α-regulated vascular endothelial growth factor signaling in mice.
abstract: Huanglian-Jie-Du-Tang (HJDT) is a traditional Chinese herbal formula which is widely used clinically. In this study, we investigated the effects of an aqueous (HJDTaq) and an ethanolic (HJDTet) extract of HJDT on chronic brain injury after focal cerebral ischemia in mice. The ischemia was induced by occlusion of the right middle cerebral artery for 30 min. HJDTaq (4 g/kg) and HJDTet (200, 400, 800 mg/kg) were orally administered for 21 d from day 7 before ischemia to day 14 after ischemia. The survival rate decreased to less than 50% at 35 d after ischemia. HJDTet at 400 mg/kg increased the survival rate. HJDTaq (4 g/kg) and HJDTet (400, 800 mg/kg) significantly attenuated the neurological dysfunction, brain atrophy and infarct volume after ischemia. There were few cells positive for CD31, hypoxia-inducible-factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and Flk-1 in the sham control. After ischemia, the number increased. HJDTaq (4 g/kg) and HJDTet (400 or 800 mg/kg) further increased the numbers of CD31, HIF-1α, VEGF and Flk-1-positive cells in the ischemic hemisphere. We conclude that HJDTaq and HJDTet have neuroprotective effects on chronic brain injury after focal cerebral ischemia and lead to accelerated angiogenesis by HIF-1α-regulated VEGF signaling.
authors.affiliation: Department of Pharmacology, Zhejiang Medical College, Hangzhou, China.
authors.forename: Yilu
authors.initials: Y
authors.lastname: Ye
authors.forename: Chunyan
authors.initials: C
authors.lastname: Huang
authors.forename: Lili
authors.initials: L
authors.lastname: Jiang
authors.forename: Xiangdi
authors.initials: X
authors.lastname: Shen
authors.forename: Shanyong
authors.initials: S
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Rao
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D020208:Brain Injury, Chronic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D045424:Complex Mixtures / Q000494:pharmacology / Q000627:therapeutic use*; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D000431:Ethanol / Q000737:chemistry; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D015398:Signal Transduction; D012997:Solvents / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D045424:Complex Mixtures; D004365:Drugs, Chinese Herbal; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018696:Neuroprotective Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012997:Solvents; D042461:Vascular Endothelial Growth Factor A; C061676:oren gedoku to; C467480:vascular endothelial growth factor A, mouse; D014867:Water; D000431:Ethanol; D040301:Vascular Endothelial Growth Factor Receptor-2