Experimental Research On Antidepression And Prokinetic Effect Of Paeoniflorin

Objective:This research is in order to investigate whether paeoniflorin can exert antidepression and prokinetic effect simultaneously similar to Si-Ni-San and Chaihu-Shugan-San.Effects of paeoniflorin on behavioral response、monoamine neurotransmitters both in plasma and hippocampus.plasma BDNF、SOD、MDA、ghrelin and motilin、HPA axis and NO in hippocampus of rats subjected to forced swim test were assessed.Meanwhile gastrointestinal motility of rats both in vivo and in vitro were observed.The results of this research were meaningful in research and development of new antidepressants.Methods:1.40 Sprague Dawley rats were randomly divided into 4 groups,including normal control group、model group、fluoxetine group and paeoniflorin group,10 rats in each group.Apart from normal control group,rats in other three groups were subjected to acute stress of 15 minutes forced swimming.Rats in model group were given normal saline lml/1OOg,while rats in fluoxetine and paeoniflorin groups were given fluoxetine 20mg/kg and paeoniflorin l0mg/kg respectively through gavage.Immobility time in 5min forced swim test and distance travelled in open field test were used to evaluate the behavioral response of rats.Monoamine transmitters both in plasma and hippocampus、plasma BDNF、SOD、MDA and NO in hippocampus and HPA axis were assayed.In this experiment fluoxetine was used as the positive control.Through this experiment we investigate the antidepression effects of paeoniflorin and the possible mechanism.2.71 Sprague Dawley rats were randomly divided into 7 groups,including normal control group、model group、fluoxetine group、low dose paeoniflorin group、middle dose paeoniflorin group、high dose paeoniflorin group and mosapride group,11 rats in normal control group and 10 rats in all other groups.Except rats in normal control group,rats in all other groups were subjected to acute stress of 15min forced swimming.Rats in model group were given normal saline 1ml/100g,while rats in fluoxetine group、low dose paeoniflorin group、middle dose paeoniflorin group、high dose paeoniflorin group and mosapride group were given fluoxetine 20mg/kg、paeoniflorin 10mg/kg、20mg/kg、40mg/kgandmosapride10mg/kg respectively.Gastrointestinal motility(gastric emptying and intestinal transit)of rats in vivo were recorded and mosapride was used as positive control.Plasma ghrelin and motilin were assayed.Through this experiment we are in order to investigate wether paeoniflorin has prokinetic effect similar to Sini San and the possible mechanism.3.The jejuna from healthy rats were removed and the amplitudes of intestinal peristalsis were detected with the multilead physiological recording instrument.Paeoniflorin with different concentrations were added into the solution in which the jejunum was immersed in order to observe the effect of paeoniflorin on the intestinal motility in vitro.Neostigmine and paeoniflorin were added into another bath successively in order to investigate the effect of paeoniflorin on hyperperistalsis model of rats.Results:1.Compared with normal control group,immobility time of rats in model group in 5min forced swim test increased and distance travelled in open field test decreased obviously.Plasma and hippocampus 5-HT、NE、DA reduced,while CRH、ACTH、corticosterone elevated both in plasma and hippocampus of rats in model group.Plasma BDNF and SOD decreased,while plasma MDA and hippocampus NO increased in rats in model group.Compared with model group,fluoxetine and paeoniflorin can reverse these abnormal changes.2.Paeoniflorin can promote gastric emptying and intestinal transit of forced swimming rats in vivo and increase plasma ghrelin and motilin level which were decreased in forced swimming rats.The prokinetic effect of paeoniflorin is similar to mosapride.3.After administration of different concentration paeoniflorin,amplitude of jejunal contraction significantly increased compared with pre-administration of paeoniflorin and the higher the concentration is,the larger the amplitude is.But when we used neostigmine to stimulate the jejunal contraction,paeoniflorin can reverse this effect.Conclusion:1.Immobility time in 5min forced swim test of rats subjected to 15min forced swim increased and distance travelled decreased in open field test,which indicate that 15min forced swimming can successfully establish depression model.2.Paeoniflorin may exert antidepression effect which was analogous to fluoxetine.This effect may be related to upregualtion of plasma and hippocampus 5-HT、NE、DA、plasma BDNF、SOD and dowregulation of plasma and hippocampus CRH、ACTH、corticosterone、plasma MDA and hippocampus NO.3.Paeoniflorin can promote gastrointestinal movement of forced swimming rats and this effect maybemadethroughincreasingplasmaghrelinandmotilin.4.Paeoniflorin can increase amplitude of jejunal contraction of healthy rats and this effect is dose dependent.But when we used neostigmine to induce hyperperistalsis of jejunal muscle,paeoniflorin can reverse this effect.