Ganoderma lucidum mediates microglial polarization and ameliorates experimental autoimmune encephalomyelitis by reducing oxidative stress and inhibiting NF-κB/STAT3 pathway

Multiple Sclerosis (MS) is a neuroinflammatory disease affecting the central nervous system (CNS), for which effective therapeutic strategies remain limited. Ganoderma Lucidum (GL) is a nature healthy food supplement whose effects on MS remain unknown. Using an experimental autoimmune encephalomyelitis (EAE) mouse model, we tested the hypothesis that GL could mitigate MS by inhibiting microglial activation and promoting a shift toward an anti-inflammatory M2-like phenotype. We demonstrate that early preventive administration of GL significantly reduced disease severity, inflammatory infiltration, demyelination, and microglial activation and polarization by promoting M2-like polarization in the spinal cord of EAE mice. Furthermore, using in vitro cellular experiments, GL revealed antioxidant and anti-inflammatory effects by scavenging superoxide (O₂·^-), nitric oxide (NO·) and peroxynitrite (ONOO^-) and down-regulated the expression of IL-1β, TNF-α, IL-6, COX2, and iNOS in the LPS-stimulated microglial cells. GL inhibited the expression of nuclear factor-κB/signal transducer and activator of transcription 3 (NF-κB/STAT3). Taken together, Ganoderma lucidum is a promoting antioxidant and anti-inflammatory healthy supplement to inhibit microglial activation and attenuate the severity and progress of MS pathogenesis by reducing oxidative stress and modulating NF-κB/STAT3 signaling pathways.