Diosgenin ameliorates cellular and molecular changes in multiple sclerosis in C57BL/6 mice

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Multiple sclerosis (MS) is a demyelinating CNS disease with no current remyelination treatments.
• Diosgenin, a herbal compound, exhibits anti-inflammatory and antioxidant properties and promotes myelin growth in vitro.
• Its in vivo effects on myelination, neuroprotection, and mechanisms in experimental autoimmune encephalomyelitis (EAE), a model for MS, are largely unstudied.

Purpose of the Study:

• To investigate the therapeutic potential of diosgenin in EAE, focusing on its effects on clinical signs, myelination, and neuroprotection.
• To elucidate the underlying cellular and molecular mechanisms of diosgenin's action in the EAE model.

Main Methods:

• EAE was induced in C57BL/6 mice using myelin oligodendrocyte glycoprotein (MOG).
• Mice received daily oral diosgenin (100 mg/kg) from symptom onset until day 18 post-immunization.
• Histopathological analysis (H&E, LFB, Bielschowsky's silver staining) and ELISA were used to assess inflammation, demyelination, axonal loss, and specific molecular markers (TNFα, MMP-9, IL-17, ADNP, MAP1LC3A).

Main Results:

• Diosgenin treatment significantly reduced EAE clinical scores from days 15-18 (p < 0.001).
• Significant reductions in spinal cord inflammation, demyelination, and axonal loss were observed in the diosgenin group (p < 0.05).
• Diosgenin decreased serum and spinal cord TNFα and spinal cord MMP-9 levels (p < 0.01) but did not significantly alter IL-17, ADNP, or MAP1LC3A levels.

Conclusions:

• Diosgenin ameliorates EAE clinical symptoms by reducing neuroinflammation, demyelination, and axonal degeneration.
• The therapeutic effects are mediated through anti-inflammatory pathways, not significantly through the investigated neuroprotective markers.
• Diosgenin shows promise as a potential therapeutic agent for MS, potentially offering both anti-inflammatory and remyelinating benefits.