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Albiflorin Attenuates Neuroinflammation and Improves Functional Recovery After Spinal Cord Injury Through Regulating LSD1-Mediated Microglial Activation and Ferroptosis

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Abstract

Spinal cord injury (SCI) is a serious, prolonged, and irreversible injury with few therapeutic options. Albiflorin (AF) possesses powerful pharmacodynamic properties and exerts protective effects against neuroinflammation. However, no research has examined the neuroprotective effect of AF following SCI. Rats were received laminectomy to establish SCI animal model and treated with AF (20 mg/kg and 40 mg/kg). Behavioral experiments were conducted to assess the impacts of AF on motor function after SCI in rats. Hematoxylin–eosin (HE) staining, Nissl staining, and Prussian Blue staining were performed to observe histological changes, neuronal damage, and iron deposition, respectively. Transmission electron microscope was adopted to observe the ultrastructure of spinal cord tissues. Immunofluorescence assay was performed to examine neurons and microglia. ELISA assay was used to examine the production of cytokines. Western blot assay was used to detect the expression level of ferroptosis-related proteins. Microglia BV-2 cells were induced by LPS to mimic the neuroinflammatory condition. Cell viability was assessed by CCK-8 assay, and lipid peroxidase level was measured by C11 BODIPY 581/591 staining. Molecular docking technology was utilized to confirm the relationship between AF and LSD1. AF improved the motor functional recovery after SCI in rats. Meanwhile, AF attenuated neuron apoptosis and microglia activation, reduced the production of pro-inflammatory cytokines and iron accumulation, and inhibited spinal cord ferroptosis following SCI in rats. LSD1 was verified to be a target protein of AF, and AF could concentration-dependently downregulate LSD1 expression in injured spinal cords in vivo and LPS-induced BV-2 cells in vitro. In addition, AF not only inhibited ferroptosis through reducing lipid peroxidase and iron levels and regulating ferroptosis-related proteins, but also inhibited microglial activation and reduced pro-inflammatory cytokines production in LPS-induced BV-2 cells; however, these changes were partly counteracted by LSD1 overexpression. AF could reduce microglial activation and ferroptosis, attenuate neuroinflammation, and improve functional recovery following SCI by downregulating LSD1, providing novel therapeutic strategies for the treatment of SCI.

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No datasets were generated or analysed during the current study.

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Authors and Affiliations

  1. Department of Orthopedics, Dongzhimen Hospital Beijing University of Chinese Medicine, 116 Cuiping West Road, Tongzhou District, Beijing, 101121, China

    Longyu Zhang, Jiao Xu, Shi Yin, Qiang Wang, Zhiwei Jia & Tianlin Wen

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  1. Longyu Zhang
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  2. Jiao Xu
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  3. Shi Yin
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  4. Qiang Wang
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  5. Zhiwei Jia
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  6. Tianlin Wen
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Contributions

TW conceived the idea and designed this study. LZ, JX, SY, QW and ZJ did the experiments and analyzed the data together. The manuscript was written by LZ and JX. TW was involved in revising the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Tianlin Wen.

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All animal procedures conformed to the ARRIVE guidelines 2.0, and were approved by the Institutional Animal Care and Use Committee of Dongzhimen Hospital Beijing University of Chinese Medicine (Approval No. IACUC-2022036–11).

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Zhang, L., Xu, J., Yin, S. et al. Albiflorin Attenuates Neuroinflammation and Improves Functional Recovery After Spinal Cord Injury Through Regulating LSD1-Mediated Microglial Activation and Ferroptosis. Inflammation (2024). https://doi.org/10.1007/s10753-024-01978-8

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  • DOI: https://doi.org/10.1007/s10753-024-01978-8

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