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

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.