α-Mangostin Inhibits α-Synuclein-Induced Microglial Neuroinflammation and Neurotoxicity

Microglia-mediated neuroinflammation induced by alpha-synuclein in the substantianigra likely either initiates or aggravates nigral neuro degeneration in Parkinson's disease (PD). We aimed to explore the effects of alpha-mangostin (alpha-M), a polyphenolicxanthone derivative from mangosteen on alpha-synuclein-stimulated DA neurodegeneration. Primary microglia, mesencephalic neuron, mesencephalic neuron-glianeuronal cultures, and transwell co-cultures were prepared separately. Liquid scintillation counting was used to determine the radioactivity in DA uptake. Enzyme-linked immunosorbent assay (ELISA) was performed in the IL-1 beta, IL-6, and TNF-alpha assay. The expression of proteins was analyzed by Western blot. alpha-M inhibited the increased levels of pro-inflammatory cytokines, NO, and ROS in alpha-synuclein-stimulated primary microglia. Mechanistic study revealed that alpha-M functioned by inhibition of nuclear factor kappa B (NF-kappa B) and NADPH oxidase. Further, alpha-M protected alpha-synuclein-induced microglial and direct neurotoxicity. Although detailed mechanisms remain to be defined, our observations suggest a potential compound, which inhibits microglial activation induced by alpha-synuclein by targeting NADPH oxidase, might be a therapeutic possibility in preventing PD progression.