Neuroprotective Effects Of Paeonol On MPTP Induced Parkinson's Disease In Mice

Objective:The present study was designed to establish a mouse model of Parkinson's disease(PD)established by MPTP,and to explore preliminary the neuroprotective effects of paeonol on the mice of PD.Methods:The forty SPF of adult male C57BL/6 mice(18–20 g)were randomly divided into control group,MPTP only group,MPTP + paeonol group and paeonol only group four groups.MPTP only group,wherein mice received intraperitoneal injections of MPTP(25 mg/kg)followed by probenecid(250 mg/kg)once a day for five consecutive days(Days 1–5)to induce the PD mouse model;MPTP + paeonol group,wherein mice received paeonol(20 mg/kg)orally for 21 days(Days 1–21)and were injected with MPTP(similar to the MPTP only group);and paeonol only group,wherein mice received oral paeonol(similar to the MPTP + paeonol group)for 21 days.Control group,wherein mice were treated with corresponding solvent;Probenecid was injected 30 min prior to MPTP injection,and paeonol was administrated orally 1 h prior to MPTP injection.The rotarod test was performed on Days 4 and 20;The open-field test was implemented on Days 5 and 21,the number of crossings,grooming behaviors,rearing behaviors,and the duration of immobility were determined.The amount of tyrosine hydroxylase(TH),microglia,IL-1?,and BDNF in the substantia nigra pars compacta(SNpc)were assessed by immunohistochemical staining.The SOD,CAT,and GSH activity in the midbrain were measured by spectrophotometrically.Results1.Effect of paeonol on the behavior of mice with MPTP induced PD on the rotarod test.The MPTP group showed significantly decreased retention times compared to the control group on Days 4 and 20(P<0.01).However,the MPTP + paeonol group showed distinct improvements in motor performance on Day 20 compared to the MPTP only group(P<0.01),but did not show improvement on Day 4.Comparatively,the paeonol only group showed behavioral performances that were resemble those in the control group(P > 0.05).2.Effect of paeonol on the behavior of mice with MPTP induced PD on the open-field test.The MPTP only group showed apparent reductions in locomotor activity,rearing,and grooming,and increases in the duration of immobility on Days 5 and 21 compared to the control group(P < 0.01).The MPTP + paeonol group had significantly improved the behavioral deficits compared to the MPTP only group on Day 21(P < 0.01).3.Paeonol attenuated the MPTP induced loss of dopaminergic neurons.The numbers of TH positive cells remarkably decreased in the MPTP only group compared to the control group(P < 0.01).However,the numbers of TH positive cells obviously rised in the MPTP + paeonol group compared to the MPTP only group(P < 0.01).No differences were found between the paeonol only group and the control group(P > 0.05).4.Paeonol attenuated the MPTP induced oxidative stress.MPTP significantly reduced the levels of SOD,CAT,and GSH compared to in the control group(P < 0.01).Treatment with paeonol for 21 days significantly restored the activity of SOD,CAT,and GSH in the MPTP + paeonol group compared to the MPTP only group(P < 0.01).However,no significant differences were found between the control group and the paeonol only group(P > 0.05).5.Paeonol attenuated the MPTP induced neuroinflammation.The numbers of Iba1-positive and IL-1?-positive cells remarkably increased in the MPTP only group compared to in the control group(P<0.01).However,the numbers of Iba1-positiveand IL-1?-positive cells obviously decreased in the MPTP + paeonol group compared to in the MPTP only group(P < 0.01).No differences were found between the paeonol only group and the control group(P > 0.05).6.Paeonol attenuated the MPTP induced loss of BDNF.The numbers of BDNF positive cells remarkably decreased in the MPTP only group compared to in the control group(P < 0.01).The numbers of BDNF positive cells apparently increased in the MPTP + paeonol group compared to the MPTP only group(P < 0.01).No differences were found between the paeonol only group and the control group(P > 0.05).Conclusion:1.The PD mouse model could be induced successfully by injecting of MPTP,oxidative stress and inflammation may be involved in the progression of PD.2.Paeonol has neuroprotective effects against MPTP-induced PD in mice,may be related to paeonol's ability to the reduction the oxidative stress and neuroinflammation,and the increase of BDNF in the SNpc.