| ObjectiveWendan tablets,the empirical formula of Prof.Xian Shaoxiang of the first affiliated Hospital of Guangzhou University of Chinese Medicine,was made with clinical experience and principles of Wendan decoction composition and indication in Three Categories of Pathogenic Factors of Diseases.With the characters of marked curative effect,no side-effects and cheap,Wendan tablets,which had been approved for hospital preparations since 1998,was welcome by patients and mainly used for anxiety with phlegm-heat syndrome.In view of the marked curative effect and acceptability of Wendan tablets,.new drugs development of Wendan tablets is necessary for market circulation and anxiety treatment.This paper aims to provide experimental basis for new drugs study of Wendan tablets by studying the literature research of WenDan decoction and anxiety and probing the relationship of action mechanism and concentration-response from pharmacological effect experiments.MethodsThis paper divides into literature research and experimental research.Literature research includes a comprehensive review of Wendan decoction and anxiety literature in China and abroad,the introduction of the relationship of Wendan decoction and Wendan tablets by studying ancient and modern physicians' academic thoughts and clinical applications,and the summary of the latest research progress of anxiety from aspects of epidemiology of pathogenesis,diagnosis and treatment.Experimental research divides into pharmacodynamics and mechanism study,mainly to explore the intervention effect of Wendan tablets by doing a series of pharmacodynamic experiments,such as Dimefline resistance to convulsions experiment,Isoniazid resistance to convulsions experiment,the isolation induced aggression experiment,the light-dark transition test,social interaction experiment,open field experiment,Vogel water conflict experiment,EPM experiment.From the aspect of mechanism study,the action mechanism of Wendan tablets is detected from different pathways and target spots by studying contents changes of superoxide dismutase(SOD),malondialdehyde(MDA),neurotransmitter ?-aminobutyric acid(GABA),glutamate(Glu),influences on cycle protein in brain tissue dependent protein kinase 5(Cdk5),activator p35 and p39's combination ability and expression of pathway.Results1.Results of WenDan tablets pharmacodynamics1.1 Anti-convulsantsDimefline resistance to convulsions experimentCompared with control group,positive control group and Wendan tablets-treated groups had longer latent period of convulsion.The results showed that high dose Wendan tablets-treated group and Anshen Wendan pill-treated group had significant differences(P<0.05)and the latent period of death in high dose Wendan tablets-treated group and diazepam-treated group was significantly prolonged(P<0.05 or P<0.01).There was no statistical significance for comparing 'Wendan tablets-treated groups only(P>0.05),while the latent period of convulsion and death in high dose Wendan tablets-treated group were longest.There were no statistical significance for comparing high dose Wendan tablets-treated group,Anshen Wendan pill-treated group and diazepam-treated group(P>0.05),while the latent period of death in high dose Wendan tablets-treated group was longer than Anshen Wendan pill-treated group,and the latent period of convulsion and death in diazepam-treated group were longer than high dose Wendan tablets-treated group.Isoniazid resistance to convulsions experimentCompared with control group,high dose Wendan tablets-treated group and diazepam-treated group had longer latent period of convulsion and different groups had significant difference(P<0.05 or P<0.01).In addition,the latent period of death of high dose Wendan tablets-treated group and diazepam-treated group was significantly prolonged(P<0.05 or P<0.01).There were no statistical significance by comparing different Wendan tablets-treated groups(P>0.05),while the high dose Wendan tablets-treated group had the longest latent period of convulsion and death.There were no statistical significance for comparing high dose Wendan tablets-treated group,Anshen Wendan pill-treated group and diazepam-treated group(P>0.05),while the latent period of convulsion and death in high dose Wendan tablets-treated group was longer than Anshen Wendan pill-treated group,and the latent period of convulsion and death in diazepam-treated group were longer than high dose Wendan tablets-treated group.1.2 Anti-anxietyThe isolation induced aggression experimentCompared with model control group,attack amounts and attack time in positive control group and Wendan tablets-treated groups were reduced.The results showed that the attack amounts in high dose Wendan tablets-treated group,Anshen Wendan pill-treated group were significantly different with model group(P<0.05),the attack time of Wendan tablets-treated groups and positive control group were also significantly different with model group(P<0.05 ? P<0.01).There were no difference in Wendan tablets-treated groups(P>0.05).Compared with Anshen Wendan pill-treated group and diazepam-treated group,'there was no difference in high dose Wendan tablets-treated group(P>0.05).The light-dark transition testCompared with control group,there was no significantly difference in transition amounts in the Anshen Wendan pill-treated group,diazepam-treated group and Wendan tablets-treated group(P>0.05).There were significant differences in each groups((P<0.05 or P<0.01),in which the time of mice of Wendan tablets-treated group and positive control group in light box were longer than control group.There were no differences in Wendan tablets-treated groups(P>0.05),and no differences in Wendan tablets-treated groups compared with positive control group(P>0.05).Social interaction experimentCompared with the control group,the time for mice to contact with each other in Wendan tablets-treated groups and positive control group were significantly prolonged.There were significant differences in high dose Wendan tablets-treated group and diazepam-treated group(P<0.05 or P<0.01),while no significant difference in Wendan tablets groups(P>0.05)and between high dose Wendan tablets-treated groups and positive control group(P>0.05).Open field experimentCompared with the control group,movement distance of Wendan tablets-treated groups and positive medicine control group were significantly prolonged.There were significant differences in high/low dose Wendan tablets-treated group,Anshen Wendan pills-treated group and diazepam-treated group compared with the control group(P<0.05 or P<0.01).Compared with control group,WenDan tablets of high dose Wendan tablets-treated group and two positive control groups had limbs of mice turned up a lot from the ground,which was with significant difference(P<0.05).There were no differences in Wendan tablets-treated group and no differences in high dose Wendan tablets-treated groups compared with positive control groups(P>0.05).Vogel water conflict experimentCompared with the control group,times of electric shock increased in both Wendan decoction-treated group and positive control group.There were significant differences in high dose Wendan tablets-treated group,Anshen Wendan pills-treated group and diazepam-treated group compared with the control group(P<0.05 or P<0.01).There were no differences in Wendan tablets-treated groups(P>0.05),and no differences in high dose Wendan tablets-treated groups compared with positive control groups(P>0.05).EPM experimentCompared with normal control group,the time percentage and number percentage of mice got into the groove of opening arms in model control groups were significantly reduced(P<0.01).Compared with model control group,the time percentage and number percentage of mice got into the groove of opening arms in Wendan tablets-treated groups were significantly increased(P<0.01 or P<0.05).There were no marked differences in Wendan tablets-treated groups(P>0.05),and no differences in Wendan tablets-treated groups compared with two positive control groups(P>0.05).2.Results of WenDan tablets anti-anxiety mechanism Influence of WenDan tablets in the content of SOD and MDA on EPM experimental rats' brainCompared with normal control group,the activity of SOD in model control group decreased,while MDA content increased.All these differences were statistically significant(P<0.01).Compared with normal control group,there was no statistical significance in diazepam-treated group on activity of SOD and MDA content(P>0.05).Compared with normal control group,Wendan tablets-treated groups had the potential to increase activity of SOD in EPM experimental mice,but no with statistical significance(P>0.05).High/low dose Wendan tablets-treated groups reduced MDA content significantly(P<0.05 or P<0.01).Compared with normal control group,activity of SOD increased and MDA content reduced to normal levels,leading to statistical significance(P<0.05).There were no marked differences in Wendan tablets-treated groups(P>0.05),and no differences in Wendan tablets-treated groups compared with two positive control groups(P>0.05).Influence of WenDan tablets in the content of GABA and Glu on EPM experimental rats' brainCompared with normal control group,GABA content in model control group was reduced and Glu content was higher,and these differences were statistically significant(P<0.01).Compared with model control group,Wendan tablets could increase GABA levels in EPM experimental mice,especially in high dose group(P<0.01),which reduced content of Glu obviously(P<0.05).Compared with model group,the diazepam-treated group increased GABA levels and lower content of Glu to normal level,and these differences were statistically significant(P<0.01 or P<0.05).There were no significant difference in Wendan tablets-treated groups(P>0.05),and no significant differences in Wendan tablets-treated groups compared with two positive control groups(P>0.05).Influence of WenDan tablets in the Cdk5/P35 pathways on EPM experimental rats' brainCompared with normal control group,model control group had higher Cdk5 expression levels,whose difference was statistically significant(P<0.01).Compared with model control group,Cdk5 protein expression level dropped in Wendan tablets-treated groups,especially in high dose group(P<0.01).Compared with normal control group,Anshen Wendan pills and diazepam reduced Cdk5 expression level,and make it close to normal,the difference was statistically significant(P<0.01).For the expression of protein p35,it had significant difference in Anshen Wendan pill-treated group(P<0.01),while no significant difference in other groups compared with model control group with p35 having the trend to decrease(P>0.05).For the expression of protein p39,there were no significant differences in Wendan tablets-treated groups,Anshen Wendan pills-treated group and diazepam—treated group compared with normal control group and model control group(P>0.05).Conclusion1.Professor Xian Shaoxiang made this empirical formula,Wendan tablets,based on Wendan decoction,and treated anxiety by the way of phlegm heat treatment.All of these conformed to the theory of etiology and pathogenesis and syndrome differentiation of traditional Chinese medicine of anxiety.2.Anti-anxiety pharmacodynamics research on Wendan tablets:from“Dimefline resistance to convulsions experiment,Isoniazid resistance to convulsions experiment,the isolation induced aggression experiment,the light-dark transition test,social interaction experiment,Open field experiment,Vogel water conflict experiment,EPM experiment",the pharmacodynamics of Wendan tablets were discussed.The results showed that Wendan tablets had its good to anti-anxiety and anti-convulsants through effective intervention.The experimental data also showed that high dose Wendan tablets-treated group had better efficacy than Anshen Wendan pills-treated group.3.The research about the mechanism of Wendan tablets on anti-anxiety effect:under the stimulation of EPM experiment,action mechanism of Wendan tablets from different pathways and target spots was studied.1).EPM significantly reduced the activity of SOD of anxiety model mice,while MDA content increased significantly.It showed that oxygen free radical defense system function decreased markedly so that it can't effectively remove oxygen free radicals,leading to the increase of MDA content.With the intervention of Wendan tablets,SOD activity and MDA content improved,showed that Wendan tables may reduce the damage from free radicals and protect nerve cells for improving the symptom of anxiety by reducing MDA levels and increasing the activity of SOD.These experiment results had also proved the Pharmacodynamics of Wendan tablets.2).GABA levels in the model group reduced,making the excitement of neurons disorder,and leading to the onset of anxiety.In addition,Wendan tablets played a role of the anti-anxiety by elevating levels of GABA and reducing Glu content.All these phenomena showed that Wendan tablets may regulate the dynamic balance of excitement and inhibition to play a role of anti-anxiety by increasing the content of inhibitory neurotransmitters.3).The experimental results showed that stress stimulation can strengthen the expression level of Cdk5/p35,while WenDan tablets reduced the expression of Cdk5/p35 by reducing action of Cdk5/p35 for achieving anti-anxiety effect.The process had nothing to do with p39,and the reason for this phenomenon might be p35 had stronger affinity with Cdk5.In addition,Wendan tablets had significant effects on GABA and Cdk5/p35 pathways,whose combination ability might be the reasons for anti-anxiety effect. |
PDF Full Text Request