title: Neuroprotective effect of the hairy root extract of Angelica gigas NAKAI on transient focal cerebral ischemia in rats through the regulation of angiogenesis.
abstract: BACKGROUND
  In this study, we investigated the neuroprotective effect of the hairy root extract of Angelica gigas NAKAI (Angelica Gigantis Radix) on transient focal cerebral ischemia in rats through the regulation of angiogenesis molecules.
  
  
  METHODS
  Male Sprague-Dawley rats were induced focal cerebral ischemia by a transient middle cerebral artery occlusion (tMCAO) for 90 min, and then orally administrated with the water extract of A. gigas hairy roots (AG). After 24 h reperfusion, infarction volume and the changes of BBB permeability were measured by TTC and Evans Blue (EB) staining. The neuronal cell damage and the activation of glial cells were assessed by immunohistochemistry in the ischemic brain. The expression of angiogenesis-induced proteins such as angiopoietin-1 (Ang-1), and vascular endothelial growth factor (VEGF), inflammatory protein such as intercellular adhesion molecule-1 (CAM-1), tight junction proteins such as ZO-1, and Occludin and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT were determined in the ischemic brains by Western blot, respectively.
  
  
  RESULTS
  The treatment of AG extract significantly decreased the volumes of brain infarction, and edema in MACO-induced ischemic rats. AG extract decreased the increase of BBB permeability, and neuronal death and inhibited the activation of astrocytes and microglia in ischemic brains. AG extract also significantly increased the expression of Ang-1, Tie-2, VEGF, ZO-1 and Occludin through activation of the PI3K/Akt pathway. AG extract significantly increased the expression of ICAM-1 in ischemic brains.
  
  
  CONCLUSIONS
  Our results indicate that the hairy root of AG has a neuroprotective effect in ischemic stroke.
authors.affiliation: Department of Herbology, College of Korean Medicine, Dongguk University, Gyeongju, 780-714, South Korea. taewoo2080@gmail.com.|Korean Medicine R&D Center, Dongguk University, Gyeongju, 780-714, Republic of Korea. taewoo2080@gmail.com.
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Oh
authors.affiliation: Korean Medicine R&D Center, Dongguk University, Gyeongju, 780-714, Republic of Korea. pcbg012@naver.com.
authors.forename: Ki-Ho
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Herbology, College of Korean Medicine, Dongguk University, Gyeongju, 780-714, South Korea. tenzing2@hanmail.net.
authors.forename: Hyo Won
authors.initials: HW
authors.lastname: Jung
authors.affiliation: Department of Herbology, College of Korean Medicine, Dongguk University, Gyeongju, 780-714, South Korea. yongki@dongguk.ac.kr.|Korean Medicine R&D Center, Dongguk University, Gyeongju, 780-714, Republic of Korea. yongki@dongguk.ac.kr.
authors.forename: Yong-Ki
authors.initials: YK
authors.lastname: Park
mesh_terms: D029969:Angelica; D042683:Angiopoietin-1 / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002544:Cerebral Infarction / Q000517:prevention & control; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D062793:Occludin / Q000378:metabolism; D010539:Permeability; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D018696:Neuroprotective Agents; D062793:Occludin; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D019869:Phosphatidylinositol 3-Kinases