No abstract

ScopeThe effect of α‐mangostin (α‐M), a polyphenolic xanthone isolated from mangostin, on lipopolysaccharide (LPS)‐induced microglial activation and memory impairment is explored. The possible underlying mechanisms are also investigated.Methods and ResultsCytokine production and activation of transforming growth factor activated kinase‐1 (TAK1) and nuclear factor‐κB (NF‐κB) are detected by enzyme‐linked immunosorbent assay (ELISA) or Western blot. Microglial migration and phagocytosis are evaluated with scratch wound‐healing assay and phagocytosis of fluorescent latex beads, respectively. Learning and memory abilities of mice are evaluated with the Morris water maze test. The nanomolar (100–500 nm) α‐M suppresses LPS‐induced pro‐inflammatory cytokine production and inducible nitric oxide synthase (iNOS) expression in microglia. It also inhibits LPS‐induced microglial migration and phagocytosis. α‐M rescues LPS‐caused, microglia‐mediated neuronal dendritic damage. Moreover, α‐M represses LPS‐induced toll‐like receptor 4 (TLR4) expression and activation of TAK1 and NF‐κB. In a mouse neuroinflammation model, α‐M (50 mg kg−1 day−1) shows obvious anti‐neuroinflammatory, neuroprotective, and memory‐improving effects in vivo.Conclusionα‐M inhibits microglia‐mediated neuroinflammation and prevents neurotoxicity and memory impairment from inflammatory damage. These results indicate that α‐M has great potential to be used as a nutritional preventive strategy for neuroinflammation‐related neurodegenerative disorders such as Alzheimer's disease.

No abstract