Neuroprotective effect of paeoniflorin on cerebral ischemic rat by activating adenosine A 1 receptor in a manner different from its classical agonists

Da Liu, Ke Qiang Xie, Xin Quan Ji, Yang Ye, Cheng Liang Jiang, Xing Zu Zhu

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

1. The effects of paeoniflorin (PF), a compound isolated from Paeony radix, on neurological impairment and histologically measured infarction volume following transient and permanent focal ischemia were examined in Sprague-Dawley rats. 2. In transient ischemia model, rats were subjected to a 1.5-h occlusion of the middle cerebral artery (MCA). The administration of PF (2.5 and 5mg kg -1, s.c.) produced a dose-dependent decrease in both neurological impairment and the histologically measured infarction volume. Similar results were also obtained when PF (2.5, 5, and 10mg kg -1, s.c.) was given in permanent ischemia model. 3. The neuroprotective effect of PF (10mg kg -1, s.c.) was abolished by pretreatment of DPCPX (0.25mg kg -1, s.c.), a selective adenosine A 1 receptor (A 1R) antagonist. 4. PF (10, 40, and 160mg kg -1, i.v.) had no effect on mean arterial pressure (MAP) and heart rates (HR) in the conscious rat. Additionally, PF (10 -3 mol l -1) had no effect on noradrenaline- (NA-) or high K + concentration-induced contractions of isolated rabbit primary artery. 5. In competitive binding experiments, PF did not compete with the binding of [ 3H]DPCPX, but displaced the binding of [ 3H]NECA to the membrane preparation of rat cerebral cortex. This binding manner was distinguished from the classical A 1R agonists. 6. The results demonstrated that activation of A 1R might be involved in PF-induced neuroprotection in cerebral ischemia in rat. However, PF had no 'well-known' cardiovascular side effects of classical A 1R agonists. The results suggest that PF might have the potential therapeutic value as an anti-stroke drug.

Original languageEnglish (US)
Pages (from-to)604-611
Number of pages8
JournalBritish Journal of Pharmacology
Volume146
Issue number4
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

Keywords

  • Adenosine A receptor
  • Cardiovascular side effect
  • Neuroprotective effect
  • Paeoniflorin
  • Permanent cerebral ischemia
  • Transient cerebral ischemia

ASJC Scopus subject areas

  • Pharmacology

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