Pan-MKK inhibition by myricetin disrupts microglial p38 signaling to rescue sleep deprivation-induced neuropsychiatric disturbances

We delineate the molecular pathogenesis of SD-induced neuropsychiatric impairments and establish SX as a multi-target therapeutic intervention. SX corrects behavioral deficits by suppressing hippocampal microglial M1 polarization through inhibition of p38 phosphorylation. Crucially, we identify myricetin as a novel broad-spectrum inhibitor of microglial p38 activation that directly binds p38 and disrupts MKK-mediated phosphorylation, serves as primary active constituent of SX against SD pathology.