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Updated: Jun 28, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Lupeol mitigates spinal cord injury by modulating microglial M1/M2 polarization via Na+/K+-ATPase-mediated mitophagy
Ruyin Liu1, Zongjin Yue1, Jia'an Dong1
1Department of Spinal Surgery, Henan Provincial Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou 450000, China.
Abstract:
Spinal cord injury (SCI) often results in severe disability or even death, with inflammation playing a critical role in hindering recovery. Although Lupeol is known for its potent anti-inflammatory properties, its specific role in SCI-induced inflammation remains underexplored. In this study, an in vitro inflammation model was established using LPS-stimulated BV2 microglia. Lupeol treatment effectively counteracted LPS-induced reductions in Na+/K+-ATPase (NKA) activity, suppression of mitophagy, M1 polarization of microglia, release of inflammatory factors, and increased pyroptosis. Mechanistically, Lupeol alleviated microglial inflammation by enhancing mitophagy through the activation of NKA activity. Furthermore, Lupeol upregulated NKA activity and mitophagy by activating the AMPKα2-mTOR-TFEB pathway. In vivo, a mouse model of SCI was established, and Lupeol was administered daily via intraperitoneal injection. Lupeol treatment significantly reduced neuronal loss, promoted microglial polarization from the M1 to the M2 phenotype, attenuated inflammation, and improved motor function recovery in SCI mice. In conclusion, Lupeol promotes mitophagy by enhancing NKA activity via the AMPK-mTOR-TFEB pathway, thereby suppressing the pro-inflammatory phenotype of microglia and mitigating SCI progression.
Insights
Lupeol, a natural compound, combats spinal cord injury (SCI) inflammation by boosting mitophagy and Na+/K+-ATPase activity. This reduces neuronal damage and improves motor function recovery in SCI models.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Spinal cord injury (SCI) leads to severe disability, with inflammation hindering recovery.
- The anti-inflammatory potential of Lupeol in SCI is not well understood.
Purpose of the Study:
- To investigate the therapeutic effects of Lupeol on SCI-induced inflammation and neuronal damage.
- To elucidate the underlying mechanisms of Lupeol's action, focusing on mitophagy and microglial activation.
Main Methods:
- In vitro: LPS-stimulated BV2 microglia model to assess Lupeol's effects on inflammation, NKA activity, mitophagy, and pyroptosis.
- In vivo: Mouse SCI model treated with Lupeol to evaluate neuronal survival, microglial polarization, inflammation, and motor function.
- Mechanistic studies involving the AMPKα2-mTOR-TFEB pathway.
Main Results:
- Lupeol reversed LPS-induced inflammation, pyroptosis, and M1 microglial polarization in vitro.
- Lupeol enhanced Na+/K+-ATPase (NKA) activity and mitophagy, activating the AMPKα2-mTOR-TFEB pathway.
- In vivo, Lupeol reduced neuronal loss, shifted microglia to the M2 phenotype, decreased inflammation, and improved motor function in SCI mice.
Conclusions:
- Lupeol mitigates SCI progression by enhancing NKA activity and mitophagy via the AMPK-mTOR-TFEB pathway.
- Lupeol suppresses the pro-inflammatory microglial phenotype, offering a potential therapeutic strategy for spinal cord injury.
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