Ganoderic Acids Alleviate Neuroinflammation by Targeting Myeloid Differentiation Factor 2 for Ischemic Stroke...

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Neuroinflammation is a key factor in cerebral ischemic injury and a target for stroke therapies.
• Ganoderic acids (GAs) from Ganoderma lucidum possess known anti-inflammatory effects.

Purpose of the Study:

• To investigate the neuroprotective effects of Ganoderic acids (GAs) in ischemic stroke.
• To elucidate the mechanism underlying GA-mediated neuroprotection.

Main Methods:

• Established in vivo (transient middle cerebral artery occlusion in mice) and in vitro (LPS-treated microglia) models of ischemic stroke.
• Assessed cerebral ischemic injury, microglial activation, and inflammatory cytokine expression.
• Investigated the interaction of GAs with myeloid differentiation protein 2 (MD2) and Toll-like receptor 4 (TLR4) signaling pathways (MAPK, NF-κB).

Main Results:

• GAs significantly reduced cerebral ischemic injury and inhibited microglial activation and inflammatory cytokine release.
• GA-K, a principal GA monomer, was identified as an inhibitor of the MD2-TLR4 interaction.
• MD2 overexpression was observed under ischemic conditions, and its deficiency abrogated GA-mediated neuroprotection.

Conclusions:

• Ganoderic acids, particularly GA-K, exert neuroprotection against ischemic stroke by targeting MD2 and modulating microglia-mediated neuroinflammation.
• MD2 represents a potential therapeutic target for stroke treatment.