Anshen Dingzhi prescription in the treatment of PTSD in mice: Investigation of the underlying mechanism from the perspective of hippocampal synaptic function

Shaojie Yang; Yan Qu; Juan Wang; Feng Gao; Manman Ji; Pan Xie; Aisong Zhu; Bei Tan; Xuncui Wang; Guoqi Zhu

doi:10.1016/j.phymed.2022.154139

Anshen Dingzhi prescription in the treatment of PTSD in mice: Investigation of the underlying mechanism from the perspective of hippocampal synaptic function

Phytomedicine. 2022 Jul:101:154139. doi: 10.1016/j.phymed.2022.154139. Epub 2022 Apr 30.

Authors

Shaojie Yang¹, Yan Qu¹, Juan Wang¹, Feng Gao¹, Manman Ji¹, Pan Xie¹, Aisong Zhu², Bei Tan², Xuncui Wang³, Guoqi Zhu⁴

Affiliations

¹ Key Laboratory of Xin'an Medicine, the Ministry of Education and Key Laboratory of Molecular Biology (Brain diseases), Anhui University of Chinese Medicine, Hefei, Anhui, 230038, China.
² Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang, 310053, China.
³ Key Laboratory of Xin'an Medicine, the Ministry of Education and Key Laboratory of Molecular Biology (Brain diseases), Anhui University of Chinese Medicine, Hefei, Anhui, 230038, China. Electronic address: wangxuncui@163.com.
⁴ Key Laboratory of Xin'an Medicine, the Ministry of Education and Key Laboratory of Molecular Biology (Brain diseases), Anhui University of Chinese Medicine, Hefei, Anhui, 230038, China. Electronic address: guoqizhu@gmail.com.

PMID: 35523115
DOI: 10.1016/j.phymed.2022.154139

Abstract

Background: Anshen Dingzhi prescription (ADP) is an important prescription for the treatment of mental diseases in traditional Chinese medicine and is widely used to treat neuropsychiatric disorders.

Purpose: To explore the ameliorative effect of ADP on post-traumatic stress disorder (PTSD)-like behaviors in mice and determine the underlying mechanism.

Methods: The constituents of ADP were analyzed by UPLC-Q-TOF/MS. The PTSD-like behaviors of mice subjected to single prolonged stress (SPS) were evaluated using behavioral tests. Potential pathological changes in the hippocampus were assessed by hematoxylin and eosin (H&E) staining. Western blotting and immunohistochemistry (IHC) were employed to detect the expression of proteins involved in relevant signaling pathways.

Results: Five quality control markers (ginsenoside Rg1, ginsenoside Rb1, tenuifolin, poricoic acid B, and α-asarone) were detected in the ADP solution. The ginsenoside Rg1 content in ADP was found to be 0.114 mg/g. Mice subjected to SPS showed obvious fear generalization and anxiety-like behaviors. ADP treatment prevented the behavioral changes caused by exposure to SPS. Compared with control animals, the number of normal pyramidal cells in the hippocampal CA1 region of mice exposed to SPS was decreased and the number of degenerating pyramidal cells was increased; however, ADP administration could counteract these effects. Furthermore, the protein expression of BDNF, p-TrkB, μ-calpain, PSD95, GluN2A, GluA1, p-AKT, p-mTOR, and ARC was decreased, while that of PTEN and GluN2B was increased in the hippocampus of mice subjected to SPS compared with that in control animals; however, these changes in protein expression were reversed following ADP treatment. Importantly, the ameliorative effect of ADP on PTSD-like behaviors and synaptic protein expression were inhibited by rapamycin administration.

Conclusions: ADP administration improves PTSD-like behaviors in mice and this effect may be mediated through an mTOR-dependent improvement in synaptic function in the hippocampus.

Keywords: Anshen Dingzhi prescription; PTSD; Synaptic plasticity; mTOR; μ-calpain.

MeSH terms

Adenosine Diphosphate / pharmacology
Animals
Disease Models, Animal
Hippocampus
Mice
Stress Disorders, Post-Traumatic* / drug therapy
Stress Disorders, Post-Traumatic* / metabolism
TOR Serine-Threonine Kinases / metabolism

Substances

Adenosine Diphosphate
TOR Serine-Threonine Kinases
tenuifolin diterpene