Therapeutic effect of saikosaponin on Tourette syndrome mice based on cAMP/PKA/CREB signaling pathway

CHEN Yu; WANG Jiabin; YAN Jianhong; ZHANG Ying

doi:10.3969/j.issn.1002-266X.2024.19.006

Abstract：Objective To investigate the therapeutic effect of saikosaponin(SS)on Tourette syndrome(TS)model mice based on cyclic adenosine monophosphate/protein kinase A/cAMP response element binding protein(cAMP/PKA/CREB)signaling pathway.Methods We randomly divided the mice into the control group,TS group,low-dose SS(SS-L)group,high-dose SS(SS-H)group,positive drug group,and SS-H+PKA inhibitor(H-89)group,with 10 mice in each group.Except for the control group,TS mouse models were established by intraperitoneal injection of iminodiacetonitrile solution in all other groups.After modeling,mice in the SS-L group and SS-H group were given intraperitoneal injection of 25 and 100 mg/kg SS,respectively,and gavaged with normal saline.Mice in the positive drug group were gavaged with 0.5 mg/kg haloperidol and intraperitoneally injected with normal saline.Mice in the SS-H+H-89 group were injected intra-peritoneally with 100 mg/kg SS and 5 mg/kg H-89,and were given physiological saline by gavage.Mice in the TS group and control group were intraperitoneally injected with and gavaged with equal volume of normal saline,respectively,once a day,for three consecutive weeks.The motor behavior and stereotyped behavior of mice were scored,5-hydroxytrypta-mine(5-HT),norepinephrine(NE),and dopamine(DA)in striatal tissues were detected by ELISA,the morphological changes in the brain tissues were observed by hematoxylin eosin method,tyrosine hydroxylase(TH)positive neurons in substantia nigra were detected by the immunohistochemical method,and the cAMP/PKA/CREB pathway-related protein expression was detected by Western blotting.Results Compared with the control group,the cell morphology of the TS group was disrupted,at 1,2,and 3 weeks after intervention,the motor behavior,stereotypical behavior scores,the levels of NE and DA,and the number of TH positive neurons increased in mice,but the expression of 5-HT,cAMP,PKA,and CREB were reduced(all P<0.05).Compared with the TS group,the cell morphology of the SS-L group,SS-H group,and positive control group was improved,at 1,2,and 3 weeks after intervention,the motor behavior,stereotypical behavior scores,the levels of NE and DA,and the number of TH positive neurons decreased in mice,but the expression of 5-HT,cAMP,PKA,and CREB increased(all P<0.05).Changes in various indicators of the SS-H group were reversed in the S-H+H-89 group(all P<0.05).Conclusion SS may exert therapeutic effects on TS mice by regulating the cAMP/PKA/CREB signaling pathway.