title: Neuroprotective effect of paeoniflorin on cerebral ischemic rat by activating adenosine A1 receptor in a manner different from its classical agonists.
abstract: 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. 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 5 mg 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 10 mg kg(-1), s.c.) was given in permanent ischemia model. The neuroprotective effect of PF (10 mg kg(-1), s.c.) was abolished by pretreatment of DPCPX (0.25 mg kg(-1), s.c.), a selective adenosine A1 receptor (A1R) antagonist. PF (10, 40, and 160 mg 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. 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 A1R agonists. The results demonstrated that activation of A1R might be involved in PF-induced neuroprotection in cerebral ischemia in rat. However, PF had no 'well-known' cardiovascular side effects of classical A1R agonists. The results suggest that PF might have the potential therapeutic value as an anti-stroke drug.
authors.affiliation: Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Pudong, Shanghai 201203, China.
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Liu
authors.forename: Ke-Qiang
authors.initials: KQ
authors.lastname: Xie
authors.forename: Xin-Quan
authors.initials: XQ
authors.lastname: Ji
authors.forename: Yang
authors.initials: Y
authors.lastname: Ye
authors.forename: Cheng-Liang
authors.initials: CL
authors.lastname: Jiang
authors.forename: Xing-Zu
authors.initials: XZ
authors.lastname: Zhu
mesh_terms: D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000378:metabolism; D000818:Animals; D001565:Benzoates / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000517:prevention & control*; D020128:Inhibitory Concentration 50; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D039821:Monoterpenes; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D029596:Paeonia; D018517:Plant Roots; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology; D006027:Glycosides
chemical_list: D019830:Adenosine-5'-(N-ethylcarboxamide); D001565:Benzoates; D001952:Bridged-Ring Compounds; D005960:Glucosides; D039821:Monoterpenes; D018696:Neuroprotective Agents; D043682:Receptor, Adenosine A1; D014970:Xanthines; C015423:peoniflorin; D006027:Glycosides; C051360:1,3-dipropyl-8-cyclopentylxanthine