2. Academic Validation
  3. Role of Qrich1-mediated endoplasmic reticulum stress pathway in Berberine inhibition of NF-κB activation induced by cerebral ischemia-reperfusion injury

Role of Qrich1-mediated endoplasmic reticulum stress pathway in Berberine inhibition of NF-κB activation induced by cerebral ischemia-reperfusion injury

  • J Stroke Cerebrovasc Dis. 2025 Dec 16;35(2):108528. doi: 10.1016/j.jstrokecerebrovasdis.2025.108528.
Ji Li 1,  Yongjie Zhu 2,  Jing Han 3,  Zhenshan Wang 4,  Hongbo Xue 5,  Meili Zhai 6,  Chong Liu 7
Affiliations

Affiliations

  • 1 Department of Anaesthesiology, Tianjin 4th Centre Hospital, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, China.
  • 2 Department of Pathology, First People's Hospital of Aksu, Xinjiang 843000, China.
  • 3 Medical School of Tianjin University, Tianjin 4th Centre Hospital, Tianjin 300072, China.
  • 4 Department of Anaesthesiology, Tianjin First Hospital, Tianjin 300140, China; The Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300000, China.
  • 5 Department of Vascular Surgery, Tianjin Medical University, Tianjin 300070, China.
  • 6 Department of Anaesthesiology, Tianjin Central Hospital of Gynecology Obstetrics, Gynecology Obstetrics Hospital of Nankai University, Tianjin 300100, China; Department of Anaesthesiology, Tianjin Medical University General Hospital, Tianjin 300070, China.
  • 7 Department of Anaesthesiology, Tianjin 4th Centre Hospital, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, China; School of Electronics and Information Engineering, Tiangong University, Tianjin 300387, China. Electronic address: [email protected].
PMID: 41412375 DOI: 10.1016/j.jstrokecerebrovasdis.2025.108528
Abstract

Background: With global population aging, the incidence of ischemic stroke is rising annually. However, its underlying mechanisms and effective clinical preventive and therapeutic measures remain elusive. This study investigated inflammatory mechanisms and therapeutic targets using a rat cerebral ischemia-reperfusion injury (CIRI) model, focusing on endoplasmic reticulum stress (ERS)-mediated inflammation.

Methods: A rat CIRI model was established. Neurological assessments were performed 24 h post-modeling. Histopathological analysis evaluated inflammatory cytokines (IL-1β, TNF-α) and NF-κB p65 nuclear translocation in the ischemic penumbra. Molecular profiling assessed activation of endoplasmic reticulum stress (ERS) markers (GRP78, p-PERK, p-eIF2α) and the ERS-associated transcription factor Glutamine-rich protein 1 (QRICH1). Pharmacological induction of ERS and treatment with berberine (BBR) were employed, with mechanistic studies including PERK inhibition.

Results: Neurological assessments revealed significant CIRI-induced neural deficits. Histopathology demonstrated upregulated IL-1β/TNF-α and NF-κB p65 nuclear translocation. Molecular profiling identified activation of ERS markers (GRP78, p-PERK, p-eIF2α) and a time-dependent elevation of QRICH1 post-CIRI. Pharmacological ERS induction confirmed QRICH1/PERK/NF-κB pathway activation. BBR administration significantly attenuated IL-1β/TNF-α levels, suppressed IκB-α degradation, and inhibited NF-κB nuclear translocation. Mechanistically, BBR downregulated QRICH1 upregulation and suppressed agonist-induced ERS-inflammatory cascades; these therapeutic effects were partially reversed by PERK Inhibitor.

Conclusion: These findings propose modulation of the QRICH1-ERS pathway as a promising therapeutic target for CIRI management, with BBR conferring protection by partially suppressing this axis.

Keywords

Berberine; Cerebral ischemia-reperfusion injury; Endoplasmic reticulum stress; Inflammation; QRICH1.

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