1. ¹Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, China
2. ²State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, China

Correspondence: Xing-Zu Zhu, E-mail: xzzhu@mail.shcnc.ac.cn

Received 11 March 2005; Revised 5 May 2005; Accepted 13 June 2005; Published online 8 August 2005.

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 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.
3. 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.
4. 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.
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 A₁R agonists.
6. 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.