酸枣仁水提物通过抑制GPR50调控突触可塑性改善小鼠PTSD样行为OA

AIM:To evaluate the effects of the aqueous extract of Ziziphi Spinosae Semen(ZSS)on single prolonged stress(SPS)-induced post-traumat-ic stress disorder(PTSD)-like behaviors in mice,and to explore its potential mechanism from the per-spective of hippocampal G protein-coupled recep-tor 50(GPR50)and synaptic plasticity.METHODS:The UPLC-UV method was employed to determine the content of the main components,saponin A and saponin B,in the aqueous extract of ZSS.C57BL/6 mice were randomly divided into Control group,SPS group,SPS+ZSS-L,M,H groups and SPS+PRX group.Behavioral experiments were used to evaluate PTSD-like behaviors in SPS mice.Molecular docking was employed to evaluate the stability of the bind-ing between the active ingredients in aqueous ex-tract of ZSS and GPR50.Western blot combined with immunofluorescence were applied to detect GPR50,PSD95,GluN2A,and GluN2B protein expres-sion in mouse hippocampal tissue.Bioinformatics analysis was used to predict key targets for ZSS treatment of PTSD.RESULTS:This study conducted qualitative and quantitative analyses of the main active ingredients saponin A and B in the aqueous extract of ZSS.Compared with the Control group,mice in the SPS group exhibited PTSD-like behav-iors such as anxiety,depression,and difficulty in fear memory extinction(P<0.05),with elevated ex-pression of GPR50 protein in the hippocampus and abnormal expression of synaptic plasticity-related proteins PSD95,GluN2A,and GluN2B.The aqueous extract of ZSS significantly improved PTSD behav-iors in SPS mice(P<0.05)and inhibited GPR50 ex-pression(P<0.05).A total of 209 potential targets of the aqueous extract of ZSS for treating PTSD were screened.These targets were enriched in pathways associated with functions such as inhibiting im-paired synaptic plasticity and exerting antioxidant properties.Molecular docking demonstrated that ZSS saponin A and saponin B,bind stably to GPR50.CONCLUSION:The aqueous extract of ZSS can ameliorate SPS-induced PTSD-like behaviors in mice,and its mechanism may be associated with the inhibition of GPR50 to alleviate synaptic plastici-ty impairment.