Abstract: AIM: To investigate the neuroprotective effects of paeoniflorin (PF) , the principal component of Paeoniae Radix prescribed in traditional Chinese medicine against the damage of rat middle cerebral artery occlusion (MCAO) and reperfusion through pharmacological preconditioning (PPC) and its molecular mechanisms, in order to offer novel drug targets and therapeutic strategies against ischemic stroke. METHODS: In rat MCAO and reperfusion model, the effects of PF pretreatment through PPC on the infarct volume and neurological deficits were examined. Furthermore, the mRNA or protein expression levels of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) have been examined after PF preconditioning using RT-PCR and Western Blot analyses. Finally, the protein expressions of MAPK signaling effectors were examined after PF preconditioning. RESULTS: At a dosage of 20 or 40 mg kg, PF preconditioning reduced the infarct volume dose-dependently and reversed the neurological deficits caused by ischemia. Similarly, the ameliorative effects on infarct size and neurological impairment induced by MCAO emerged as well at a time-dependent manner when PF was administered 24, 48 h or 5 d before MCAO at the dose of 20 mg kg. The over expressions ofCOX-2 mRNA and protein and 5-LOX protein in ischemia were reversed by PF preconditioning. The activation of MAPK signaling pathway was also inhibited by PF preconditioning. CONCLUSION: The PPC could be induced by PF, mimicking the effects of ischemic preconditioning. The molecular mechanisms underlying its ameliorative effects are through inhibiting the inflammation involved in arachidonic acid metabolism and the activation of MAPK signaling pathway.

Key words: middle cerebral artery occlusion, pharmacological preconditioning, arachidonic acid metabolism, cyclooxygenase-2, 5-lipoxygenase