title: Paeoniflorin improves regional cerebral blood flow and suppresses inflammatory factors in the hippocampus of rats with vascular dementia.
abstract: OBJECTIVE
  To explore the delayed neuroprotection induced by paeoniflorin (PF), the principal component of Paeoniae radix prescribed in Chinese medicine, and its underlying mechanisms in rats subjected to vascular dementia (VD).
  
  
  METHODS
  A rat model of VD was induced by bilateral common carotid arteries occlusion (BCCAO). Low-dose or high-dose PF (20 or 40 mg/kg once per day) was administrated for 28 days after VD. The behavioral analysis of rat was measured by water morris. Regional cerebral blood volume (rCBV), regional cerebral blood flflow (rCBF) and mean transit time (MTT) were measured in the bilateral hippocampus by perfusion-weighted imaging (PWI). The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were measured by commercially available enzyme-linked immunosorbent assay kits. Protein levels were evaluated by western blot analysis. mRNA levels were evaluated by real time-polymerase chain reaction. Western blotting was used to estimate p65 translocation.
  
  
  RESULTS
  The behavioral analysis showed that PF could decrease the escape latency time (P<0.05), and increase the residence time of the original platform quadrant and the across platform frequency in water maze in VD rats (P<0.05). Likewise, PF remarkably promoted the rCBV (P<0.05), rCBF and decreased per minute MTT (P<0.05) in hippocampus of VD rats. Furthermore, PF decreased the release of IL-1β, IL-6 and TNF-α as well as inhibited the mRNA expression of IL-1β, IL-6 and TNF-α in the hippocampus of VD rats (P<0.05 or P<0.01). PF also could decrease the protein expressions of inducible nitric oxide synthase and cyclooxygenase-2 in the hippocampus of VD rats (P<0.05 or P<0.01). In addition, PF signifificantly inhibited the nuclear factor κB (NF-κB) pathway in the hippocampus of VD rats.
  
  
  CONCLUSIONS
  PF signifificantly attenuates cognitive impairment, improves hippocampus perfusion and inhibits inflflammatory response in VD rats. In addition, the anti-inflflammatory effects of PF might be due to inhibiting the NF-κB pathway. PF may be a potential clinical application in improving VD.
authors.affiliation: Department of Anesthesia, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Li-Gong
authors.initials: LG
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Shen
authors.affiliation: The Fifth Hospital of Jinan, Jinan, 250021, China.
authors.forename: Hao-Feng
authors.initials: HF
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, National Research Institute of Family Planning, Beijing, 100081, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, National Research Institute of Family Planning, Beijing, 100081, China.
authors.forename: Cui-Ge
authors.initials: CG
authors.lastname: Shi
authors.affiliation: Department of Cell Biology, National Research Institute of Family Planning, Beijing, 100081, China.
authors.forename: Shu-Cheng
authors.initials: SC
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China. zhangmy2014@sina.com.
authors.forename: Meng-Yuan
authors.initials: MY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051996:Transcription Factor RelA / Q000378:metabolism; D006027:Glycosides
chemical_list: D051546:Cyclooxygenase 2; D005960:Glucosides; D018836:Inflammation Mediators; D039821:Monoterpenes; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger; D051996:Transcription Factor RelA; C015423:peoniflorin; D006027:Glycosides
keywords: cerebral blood flflow; hippocampus; paeoniflflorin; vascular dementia