title: Cardiotonic pill attenuates white matter and hippocampal damage via inhibiting microglial activation and downregulating ERK and p38 MAPK signaling in chronic cerebral hypoperfused rat.
abstract: BACKGROUND
  The cardiotonic pill (CP) is a herbal medicine composed of Salvia miltiorrhiza (SM), Panax notoginseng (PN), and Dryobalanops aromatica Gaertner (DAG) that is widely used to treat cardiovascular diseases. The present experiment was conducted to examine the effects of CP on white matter and hippocampal damage induced by chronic cerebral hypoperfusion.
  
  
  METHODS
  Chronic cerebral hypoperfusion was induced in male Wistar rats by permanent bilateral common carotid artery occlusion (BCCAo). Daily oral administration of CP (200 mg/kg) began 21 days after BCCAo and continued for 42 days. The levels of microglial activation and myelin basic protein (MBP) were measured in the white matter and hippocampus of rats with chronic BCCAo, and the expression levels of mitogen-activated protein kinases (MAPKs) and inflammatory markers such as cyclooxygenase-2, interleukin-1β, and interleukin-6 were examined.
  
  
  RESULTS
  MBP expression was reduced in the white matter and hippocampal regions of rats that received BCCAo. In contrast, reduced levels of MBP were not observed in BCCAo rats given CP treatments. The administration of CP alleviated microglial activation, the alteration of ERK and p38 MAPK signaling, and inflammatory mediator expression in rats with chronic BCCAo.
  
  
  CONCLUSIONS
  These results suggest that CP may have protective effects against chronic BCCAo-induced white matter and hippocampal damage by inhibiting inflammatory processes including microglial activation and proinflammatory mediator expression, and downreguating the hyperphosphorylation of ERK and p38 MAPK signaling.
authors.affiliation: KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea. wkjeon@kiom.re.kr.
authors.forename: Ki Mo
authors.initials: KM
authors.lastname: Lee
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Bang
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.forename: Bu Yeo
authors.initials: BY
authors.lastname: Kim
authors.forename: In Sun
authors.initials: IS
authors.lastname: Lee
authors.forename: Hyung Won
authors.initials: HW
authors.lastname: Kang
authors.forename: Won Kyung
authors.initials: WK
authors.lastname: Jeon
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D016893:Carotid Stenosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D053958:Dipterocarpaceae; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D017628:Microglia / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000378:metabolism; D053723:Panax notoginseng; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D027561:Salvia miltiorrhiza; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D015850:Interleukin-6; D004676:Myelin Basic Protein; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases