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

doi:10.12092/j.issn.1009-2501.2026.08.005

中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (8): 1053-1063.doi: 10.12092/j.issn.1009-2501.2026.08.005

• 基础研究 • 上一篇

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

高子璇¹(), 何存宝¹, 杨绍杰², 王斌¹, 朱国旗¹, 程卉³^,*(), 陈丽霞¹^,*()

1. 安徽中医药大学分子生物学（脑病）重点实验室，合肥 230012，安徽
2. 安徽中医药大学第二附属医院，合肥 230061，安徽
3. 安徽中医药大学新安医学教育部重点实验室，合肥 230038，安徽

收稿日期:2025-06-25 修回日期:2026-03-18 出版日期:2026-08-26 发布日期:2026-09-09
通讯作者: 程卉,陈丽霞 E-mail:gaozx01@qq.com;chenghuikyzx@ahtcm.edu.cn;c994743@163.com
作者简介:高子璇，女，在读硕士，研究方向：神经药理学。E-mail：gaozx01@qq.com
基金资助:
国家自然科学基金（82404890）；安徽省高等学校科学研究项目（2024AH040137，2024AH051044）；新安医学与中医药现代化研究所“揭榜挂帅”项目（2023CXMMTCM013）

Amelioration of PTSD-like behaviors in mice by the aqueous extract of Ziziphi Spinosae Semen via inhibition of GPR50 and regulation of synaptic plasticity

Zixuan GAO¹(), Cunbao HE¹, Shaojie YANG², Bin WANG¹, Guoqi ZHU¹, Hui CHENG³^,*(), Lixia CHEN¹^,*()

1. Key Laboratory of Molecular Biology (Brain Diseases), Anhui University of Chinese Medicine, Hefei 230012, Anhui, China
2. The Second Affiliation Hospital of Anhui University of Chinese Medicine, Hefei 230061, Anhui, China
3. Key Laboratory of Xin'an Medicine, Anhui University of Chinese Medicine, Hefei 230038, Anhui, China

Received:2025-06-25 Revised:2026-03-18 Online:2026-08-26 Published:2026-09-09
Contact: Hui CHENG,Lixia CHEN E-mail:gaozx01@qq.com;chenghuikyzx@ahtcm.edu.cn;c994743@163.com

摘要/Abstract

摘要：

目的: 评价酸枣仁（Ziziphi Spinosae Semen，ZSS）水提物对单次长时程应激（single prolonged stress，SPS）诱导的小鼠创伤后应激障碍（post-traumatic stress disorder，PTSD）样行为的作用，并从G蛋白偶联受体50（G protein-coupled receptor 50，GPR50）和海马突触可塑性角度探究其可能的作用机制。方法: UPLC-UV检测酸枣仁水提物中主要成分酸枣仁皂苷A、B含量；将C57BL/6小鼠随机分为正常对照组、SPS模型组、SPS+酸枣仁水提物低、中、高剂量组及SPS+帕罗西汀组，采用行为学实验评价SPS小鼠的PTSD样行为；分子对接验证酸枣仁皂苷A、B分别与GPR50结合的稳定性；Western blot联合免疫荧光检测小鼠海马组织GPR50、PSD95、GluN2A和GluN2B蛋白表达水平；生物信息分析学预测酸枣仁治疗PTSD的关键靶点。结果: 本研究对酸枣仁水提物中主要药效成分酸枣仁皂苷A、B进行了定性和定量分析；与正常组比较，SPS模型组小鼠表现出焦虑、抑郁和恐惧记忆消退困难等PTSD样行为（P<0.05），海马GPR50蛋白表达升高，突触可塑性相关蛋白PSD95、GluN2A和GluN2B表达异常，而酸枣仁水提物可明显改善SPS小鼠的PTSD样行为（P<0.05），并抑制GPR50表达（P<0.05），改善PSD95、GluN2A和GluN2B蛋白的异常表达；筛选酸枣仁水提物作用PTSD潜在靶点209个，分别富集在抑制突触可塑性损伤及发挥抗氧化特性等功能；分子对接显示酸枣仁水提物中主要成分酸枣仁皂苷A、B与GPR50结合稳定。结论: 酸枣仁水提物能改善SPS诱导的小鼠PTSD样行为，其机制可能与抑制GPR50改善突触可塑性损伤相关。

关键词: 创伤后应激障碍, G蛋白偶联受体50, 酸枣仁, 突触可塑性

Abstract:

AIM: To evaluate the effects of the aqueous extract of Ziziphi Spinosae Semen (ZSS) on single prolonged stress (SPS)-induced post-traumatic stress disorder (PTSD)-like behaviors in mice, and to explore its potential mechanism from the perspective of hippocampal G protein-coupled receptor 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 binding between the active ingredients in aqueous extract of ZSS and GPR50. Western blot combined with immunofluorescence were applied to detect GPR50, PSD95, GluN2A, and GluN2B protein expression 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 behaviors such as anxiety, depression, and difficulty in fear memory extinction (P<0.05), with elevated expression 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 behaviors in SPS mice (P<0.05) and inhibited GPR50 expression (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 impaired 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 plasticity impairment.

Key words: post-traumatic stress disorder, G protein-coupled receptor 50, Ziziphi Spinosae Semen, synaptic plasticity

中图分类号:

R749
R965.2

高子璇, 何存宝, 杨绍杰, 王斌, 朱国旗, 程卉, 陈丽霞. 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[J]. 中国临床药理学与治疗学, 2026, 31(8): 1053-1063.

Zixuan GAO, Cunbao HE, Shaojie YANG, Bin WANG, Guoqi ZHU, Hui CHENG, Lixia CHEN. Amelioration of PTSD-like behaviors in mice by the aqueous extract of Ziziphi Spinosae Semen via inhibition of GPR50 and regulation of synaptic plasticity[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(8): 1053-1063.

图/表 8

图 1

Fig.1 HPLC chromatograms of Ziziphi Spinosae Semen (ZSS) solution and standard solution A: jujuboside A; B: the aqueous extract of ZSS; C: jujuboside B.

图 2

Fig.2 The aqueous extract of Ziziphi Spinosae Semen (ZSS) improved anxiety-like behaviors in SPS mice ($ \overline{\boldsymbol{x}} $±s, n=8) A: schematic representation of the time point of administration of the ZSS; B-F: time in central area, distance in central area, center entries, total distance and mean speed of OFT; G: percentage of time in open arms in EPMT; H: movement traces of OFT. bP<0.05, compared with the control group; eP<0.05, compared with SPS group.

图 3

Fig.3 The aqueous extract of Ziziphi Spinosae Semen (ZSS) promoted the extinction of fear memory in SPS mice ($ \overline{\boldsymbol{x}} $±s, n=8) A: freezing time in the re-exposure phase; B: freezing time in the extinction phase. bP<0.05, compared with the control group; eP<0.05, compared with SPS group.

图 4

Fig.4 Potential targets and enrichment analysis of Ziziphi Spinosae Semen (ZSS) in treatment of PTSD A: active component targets and disease targets Venn diagram; B: PPI network.

图 5

Fig.5 GO and KEGG enrichment analysis of potential targets of Ziziphi Spinosae Semen (ZSS) treatment for PTSD A-C: GO analysis; D: KEGG analysis; E: drug-component-target network.

图 6 A: jujuboside A-GPR50; B: jujuboside B-GPR50.

Fig.6 Visualization of molecules docking between main components of Ziziphi Spinosae Semen (ZSS) and key targets. A: jujuboside A-GPR50; B: jujuboside B-GPR50.

图 7

Fig.7 The aqueous extract of Ziziphi Spinosae Semen (ZSS) inhibited the expression of GPR50 protein in the hippocampus ($ \overline{\boldsymbol{x}} $±s, n=6) A: representative blots; B: quantitative data of GPR50 (n=3); C-H: schematic immunofluorescence of GPR50 in the CA1, CA3 and DG region of mouse hippocampus and mean fluorescence intensity of GPR50 (Nucleus: blue; GPR50: red) (n=3). bP<0.05, compared with the control group; eP<0.05, compared with SPS group.

图 8

Fig.8 Effects of the aqueous extract of Ziziphi Spinosae Semen (ZSS) on the expression levels of PSD95, GluN2A and GluN2B proteins in mouse hippocampus ($ \overline{\boldsymbol{x}} $±s, n=3) A: representative blot and quantitative analysis of PSD95; B: representative blot and quantitative analysis of GluN2A; C: representative blot and quantitative analysis of GluN2B; bP<0.05, compared with the control group; eP<0.05, compared with SPS group.

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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

Amelioration of PTSD-like behaviors in mice by the aqueous extract of Ziziphi Spinosae Semen via inhibition of GPR50 and regulation of synaptic plasticity

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