title: Salvia miltiorrhiza extract protects white matter and the hippocampus from damage induced by chronic cerebral hypoperfusion in rats.
abstract: BACKGROUND
  Salvia miltiorrhiza (SM), an herbal plant, is traditionally used in the treatment of cardiovascular and cerebrovascular diseases in Asian countries. SM has multiple biological effects including anti-inflammatory activity. The present study is aimed at investigating the effects of SM extract in rats with chronic cerebral hypoperfusion.
  
  
  METHODS
  Chronic cerebral hypoperfusion was induced in male Wistar rats by permanent bilateral common carotid artery occlusion (BCCAo). The rats were divided into 3 groups: sham-control, BCCAo treated with vehicle, and BCCAo treated with SM extract. Vehicle or SM extract (200 mg/kg) were administered daily by oral gavage beginning on day 21 after BCCAo and continuing to day 42. Immunohistochemical analyses were used to measure Iba-1-positive microglia and myelin basic protein (MBP) in white matter and hippocampal tissue. In addition, the expression levels of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, and the toll-like receptor (TLR) pathway in the hippocampus, were analyzed by western blot.
  
  
  RESULTS
  Administration of SM extract attenuated the activation of microglial cells in the white matter and hippocampus after BCCAo. SM extract also prevented neuroinflammation after BCCAo by reducing hippocampal levels of TNF-α, IL-1β, and IL-6, and increasing the reduced levels of MBP in the white matter and hippocampus. Further, the administration of SM extract alleviated the up-regulation of hippocampal TLR4 and myeloid differentiation primary response gene 88 (MyD88) in rats with chronic BCCAo.
  
  
  CONCLUSIONS
  Our findings suggest that SM may be a promising therapeutic candidate in vascular dementia because of its protective effects against damage to the white matter and hippocampus after BCCAo.
authors.affiliation: Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 305-811, Republic of Korea. kms3167@kiom.re.kr.|Department of Biological Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143-701, Republic of Korea. kms3167@kiom.re.kr.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 305-811, Republic of Korea. fart0920@naver.com.|Department of Internal Medicine, School of Medicine, Keimyung University, 1095 Dalgubeoldae-ro, Dalseo-gu, Daegu, 704-701, Republic of Korea. fart0920@naver.com.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Bang
authors.affiliation: Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 305-811, Republic of Korea. junlee@kiom.re.kr.|Korean Medicine Life Science, University of Science & Technology, Daejeon, 34054, Republic of Korea. junlee@kiom.re.kr.
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Research, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea. hwkim8906@gmail.com.
authors.forename: Hyeon Woo
authors.initials: HW
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Research, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea. shsung@snu.ac.kr.
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Sung
authors.affiliation: Department of Biological Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143-701, Republic of Korea. jshan06@konkuk.ac.kr.
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.affiliation: Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 305-811, Republic of Korea. wkjeon@kiom.re.kr.
authors.forename: Won Kyung
authors.initials: WK
authors.lastname: Jeon
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D010477:Perfusion; D020011:Protective Agents / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D066127:White Matter / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D015850:Interleukin-6; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha