Abstract

Neuroinflammation, driven by chronic microglial activation, is a pivotal factor in neurodegenerative diseases. Osmanthus Longjing (OLJ, a green tea blend) and Osmanthus black tea (OBT, a black tea blend), rich in bioactive polyphenols, exhibit anti-inflammatory properties with potential neuroprotective effects. This study investigates their neuroprotective effects against lipopolysaccharide (LPS)-induced neuroinflammation through dual modulation of the gut-brain axis and the KEAP1/ NRF2 pathway. Oral administration of OLJ and OBT (300 mg/kg/day) attenuated LPS-induced body weight loss, suppressed hippocampal microglial activation, decreased serum pro-inflammatory cytokine levels and hippocampal oxidative stress, reduced neuronal damage, and improved recognition index (RI) in neuroinflammatory mice. Mechanistically, both teas modulated the KEAP1/NRF2 signaling pathway by reversing LPS-induced upregulation of KEAP1, NRF2, NQO1, and HO1 expression at both transcriptional and protein levels. Cecal microbiome profiles revealed that OLJ and OBT interventions ameliorated LPS-induced gut microbiota dysbiosis. OLJ specifically enriched beneficial taxa ( Dubosiella , Bifidobacterium , Eubacterium nodatum group ), while both teas suppressed Proteobacteria overgrowth. Spearman's correlation analysis established significant associations between specific microbiota, oxidative stress and cognitive markers. These findings demonstrate novel gut-brain regulatory mechanisms of traditional flower teas, positioning OLJ and OBT as functional food candidates for neuroinflammatory disorders.