2. Academic Validation
  3. Paeoniflorin Attenuates Cognitive Dysfunction and Neuroinflammation by Autophagy in Mice with SLE Induced by Imiquimod

Paeoniflorin Attenuates Cognitive Dysfunction and Neuroinflammation by Autophagy in Mice with SLE Induced by Imiquimod

  • J Inflamm Res. 2025 Oct 7:18:13945-13964. doi: 10.2147/JIR.S524710.
Tianzhen Ma 1 2,  Qian Wang 3,  Liping Zhang 4,  Xuan Chen 5,  Zhiheng Fan 5,  Yanxin Wang 3,  Xiaonan Zhang 6,  Yinjiu Huang 7,  Xinghao Lu 8,  Peipei Song 9,  Changhao Xie 3,  Jin Xi 2 10,  Baiqing Li 11,  Yuanyuan Wang 1 2
Affiliations

Affiliations

  • 1 Department of Histology and Embryology, Bengbu Medical University, Bengbu, Anhui, 233030, People's Republic of China.
  • 2 Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical University, Bengbu, Anhui, 233030, People's Republic of China.
  • 3 Department of Rheumatology and Immunology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233004, People's Republic of China.
  • 4 School of Public Health, Bengbu Medical University, Bengbu, Anhui, 233030, People's Republic of China.
  • 5 School of Clinical Medicine, Bengbu Medical University, Bengbu, Anhui, 233030, People's Republic of China.
  • 6 Department of Pathophysiology, Bengbu Medical University, Bengbu, Anhui, 233030, People's Republic of China.
  • 7 School of Life Science, Bengbu Medical University, Bengbu, 233000, People's Republic of China.
  • 8 Department of Human Anatomy, Bengbu Medical University, Bengbu, Anhui, 233030, People's Republic of China.
  • 9 School of Mental Health, Bengbu Medical University, Bengbu, Anhui, 233030, People's Republic of China.
  • 10 Bengbu Medical University Research Center, Bengbu, Anhui, 233030, People's Republic of China.
  • 11 Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu, Anhui, 233030, People's Republic of China.
PMID: 41080153 DOI: 10.2147/JIR.S524710
Abstract

Purpose: This research was designed to systematically assess the neuroprotective efficacy of paeoniflorin and clarify the molecular mechanisms using two complementary models: a TLR-7 agonist imiquimod-induced murine lupus model and lipopolysaccharide-injured HT22 hippocampal neuronal cells.

Methods: A lupus-like phenotype was induced in C57BL/6J mice through topical administration of 1.25 mg 5% (w/w) imiquimod cream to the posterior auricular region three times a week for eight consecutive weeks, paeoniflorin by gavage for 7 days, and dexamethasone by intraperitoneal injection for 7 days. Animal behavioral experiments were performed at the end of the modeling. Subsequent execution of Animals for biochemical analysis and histopathological examinations to evaluate the effects of paeoniflorin.

Results: Paeoniflorin ameliorated cognitive deficits, reduced autoantibody generation production, and hippocampal neuronal were observed in the SLE induced by the TLR-7 agonist imiquimod, accompanied by amelioration of blood-brain barrier damage. Subsequently, paeoniflorin activated Autophagy and upregulated Autophagy flux-related protein levels in mice with SLE induced by the TLR-7 agonist imiquimod. Interestingly, LPS-induced Autophagy levels in HT22 cells were downregulated, but paeoniflorin pretreatment restored its Autophagy inhibitory effect and attenuated the secretion of pro-inflammatory cytokines. Paeoniflorin activated the PI3K/Akt/mTOR pathway to restore Autophagy, and using 3-methyladenine further confirmed the mechanism of paeoniflorin's role in regulating Autophagy.

Conclusion: Paeoniflorin plays a critical neuroprotective role as demonstrated in the TLR-7 agonist imiquimod-induced murine lupus model, mediated through activation of autophagic flux via modulation of the PI3K/Akt/mTOR signaling axis.

Keywords

NPSLE; autophagy; cognitive; neuroinflammation; paeoniflorin.

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