Phillygenin inhibits neuroinflammation and promotes functional recovery after spinal cord injury via TLR4 inhibition of the NF-κB signaling pathway

Journal of Orthopaedic Translation, 2024 · DOI: https://doi.org/10.1016/j.jot.2024.07.013 · Published: July 29, 2024

Spinal Cord Injury Alternative Medicine Immunology

Simple Explanation

Spinal cord injuries (SCIs) trigger a cascade of detrimental processes, encompassing neuro- inflammation and oxidative stress (OS), ultimately leading to neuronal damage. Phillygenin (PHI), isolated from forsythia, is used in a number of biomedical applications, and is known to exhibit anti-neuroinflammation activity. PHI ameliorated SCI-induced neuroinflammation by modulating the TLR4/MYD88/NF-κB signaling pathway.

Study Duration

42 days

Participants

60 female Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
PHI significantly inhibited the inflammatory response and neuronal apoptosis while enhancing axonal regeneration and improving motor function recovery in vivo.
2
PHI inhibited the release of inflammation-related factors from polarized BV2 cells in a dose-dependent manner in vitro.
3
PHI directly targeted the TLR4 protein and inhibited inflammatory factors by inhibiting the expression of TLR4.

Research Summary

We found that PHI exerted anti- neuroinflammatory effects by inactivating the NF-κB signaling pathway by targeting TLR4. PHI can efficiently prevent microglial activation and the subsequent neuroinflammatory response. This action is achieved by targeting TLR4 and inhibiting the NF-κB pathway following SCI.

Practical Implications

Therapeutic Potential

PHI has the potential to be administered as a treatment for SCI and represents a novel candidate drug for addressing neuroinflammation mediated by microglial cells.

Novel Therapeutic Agents

Our findings have promising implications for the development of novel therapeutic agents based on the pathogenesis of SCI.

Translational Applications

We demonstrated that PHI is a potential drug candidate for the therapeutic management of SCI with promising developmental and translational applications.

Study Limitations

1
Specific mechanisms responsible for the anti-inflammatory and neuroprotective effects of PHI in SCI have yet to be elucidated.
2
Further research is needed to explore the long-term effects and optimal dosage of PHI for SCI treatment.
3
The study was conducted on rats, and further research is necessary to confirm these findings in human clinical trials.

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