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

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 A 1 receptor (A 1 R) 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 [ 3 H]DPCPX, but displaced the binding of [ 3 H]NECA to the membrane preparation of rat cerebral cortex. This binding manner was distinguished from the classical A 1 R agonists. The results demonstrated that activation of A 1 R might be involved in PF‐induced neuroprotection in cerebral ischemia in rat. However, PF had no ‘well‐known’ cardiovascular side effects of classical A 1 R agonists. The results suggest that PF might have the potential therapeutic value as an anti‐stroke drug.British Journal of Pharmacology (2005) 146 , 604–611. doi: 10.1038/sj.bjp.0706335