Alpha-Bisabolol alleviates LPS-reduced hippocampal neurogenesis and cognitive function by anti-inflammatory action...

Neuroinflammation is a key pathological process contributing to hippocampal neurogenesis impairment and cognitive dysfunction. This study aimed to evaluate the neuroprotective effects of α-Bisabolol (α-Bis), a natural sesquiterpene alcohol, on lipopolysaccharide (LPS)-induced neuroinflammation in mice. LPS administration decreased neural stem cell (NSC) proliferation, neural differentiation, cognitive dysfunction and increased NSC apoptosis. Oral administration of α-Bis ameliorated LPS-reduced hippocampal NSC proliferation, differentiation, cognitive function and LPS-induced NSC apoptosis. Mechanistically, α-Bis attenuated LPS-enhanced microglial activation and suppressed CD68 ⁺ cells with pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) but increased CD206⁺ cells with anti-inflammatory cytokines (IL-10, TGF-β) expression. In addition, α-Bis inhibited the TLR4/MAPK/NF-κB signaling cascade activated by LPS. These findings suggest that α-Bis confers neuroprotection by promoting anti-inflammatory cytokine expression from CD206⁺ microglia via downregulation of TLR4/MAPK/NF-κB signaling in the hippocampus under LPS-induced neuroinflammation, thereby restoring hippocampal neurogenesis and cognitive function impaired by LPS, highlighting its therapeutic potential for inflammation-associated neurodegenerative diseases.