2. Academic Validation
  3. Gypenoside XVII regulates apoptosis and fear extinction deficits mediated by post-traumatic stress disorder through the PERK/CHOP signaling pathway

Gypenoside XVII regulates apoptosis and fear extinction deficits mediated by post-traumatic stress disorder through the PERK/CHOP signaling pathway

  • Eur J Pharmacol. 2025 Dec 15:1009:178391. doi: 10.1016/j.ejphar.2025.178391.
Yitai Yang 1,  Jingjing Wang 2,  Shuying Wang 1,  Yueyang Chen 2,  Zemeng Li 2,  Huimin Zhang 2,  Pengbo Zhou 2,  Wei Li 2,  Dangli Ren 2,  Hongtao Sun 3
Affiliations

Affiliations

  • 1 Neurological Disease Center, Characteristic Medical Center of People's Armed Police Forces, Tianjin, 300162, China; Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 2 Neurological Disease Center, Characteristic Medical Center of People's Armed Police Forces, Tianjin, 300162, China.
  • 3 Neurological Disease Center, Characteristic Medical Center of People's Armed Police Forces, Tianjin, 300162, China; Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address: [email protected].
PMID: 41276105 DOI: 10.1016/j.ejphar.2025.178391
Abstract

Objective: Post-traumatic stress disorder (PTSD) leads to Apoptosis in the medial prefrontal cortex (mPFC). Although studies have demonstrated the neuroprotective effects of Gypenoside XVII(GP-17), the potential mechanisms of GP-17 for the treatment of PTSD remain to be elucidated. This study aimed to investigate the inhibitory effect of GP-17 on the fear state of PTSD through the PERK/CHOP pathway.

Materials and methods: Establishment of a Single Prolonged Stress (SPS) model using Sprague Dawley (SD) rats, combined with behavioral assessments, TUNEL staining, Western blot analysis, Immunofluorescence staining, and Flow cytometry analyses of a primary microglia model. This study aims to evaluate the effects of GP-17 treatment on fear and anxiety states, as well as the role of the endoplasmic reticulum (ER) stress signaling pathway, specifically protein kinase RNA (PKR)-like ER kinase (PERK), in regulating Apoptosis in rats.

Results: Research shows that GP-17 significantly reduces Apoptosis in the prefrontal cortical microglia of SPS rats by modulating the PERK-C/EBP-homologous protein (CHOP) signaling pathway. This modulation helps improve fear extinction deficits and reduces anxiety-like behavior. Additionally, GP-17 intervention effectively inhibits neuroinflammation and oxidative stress. In vitro experiments further demonstrate that GP-17 prevents tunicamycin (Tu)-induced Apoptosis related to PERK-mediated ER stress in primary rat microglia.

Conclusion: GP-17 demonstrates therapeutic potential for PTSD by modulating fear and anxiety in SPS rats through the PERK/CHOP pathway, positioning it as a promising candidate for PTSD treatment via the endoplasmic reticulum stress pathway.

Keywords

CHOP; ER stress; Gypenoside XVII; PERK; PTSD; SPS.

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