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.
- 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.
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.