title: α-Mangostin Inhibits α-Synuclein-Induced Microglial Neuroinflammation and Neurotoxicity.
abstract: Microglia-mediated neuroinflammation induced by α-synuclein in the substantianigra likely either initiates or aggravates nigral neuro degeneration in Parkinson's disease (PD). We aimed to explore the effects of α-mangostin (α-M), a polyphenolicxanthone derivative from mangosteen on α-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-1β, IL-6, and TNF-α assay. The expression of proteins was analyzed by Western blot. α-M inhibited the increased levels of pro-inflammatory cytokines, NO, and ROS in α-synuclein-stimulated primary microglia. Mechanistic study revealed that α-M functioned by inhibition of nuclear factor kappa B (NF-κB) and NADPH oxidase. Further, α-M protected α-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 α-synuclein by targeting NADPH oxidase, might be a therapeutic possibility in preventing PD progression.
authors.affiliation: Hangzhou Cancer Institute, Hangzhou Cancer Hospital, Hangzhou, 310007, Zhejiang, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Pharmacy & Medical Appliances, Hangzhou Sanatorium of PLA, No.27 Yang Gong Dike, Hangzhou, 310007, Zhejiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmacy & Medical Appliances, Hangzhou Sanatorium of PLA, No.27 Yang Gong Dike, Hangzhou, 310007, Zhejiang, China. lingjingtg@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Ling
authors.affiliation: Department of Pediatrics, Hangzhou First People's Hospital, Huansha Road, No.261, Hangzhou, 310003, Zhejiang, China. chunming_jiang@126.com.
authors.forename: Chunming
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D008636:Mesencephalon / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044004:Xanthones / Q000494:pharmacology*; D051844:alpha-Synuclein / Q000494:pharmacology*
chemical_list: D044004:Xanthones; D051844:alpha-Synuclein; D019255:NADPH Oxidases; C021053:mangostin; D004298:Dopamine
keywords: Microglia; Neurotoxicity; α-Mangostin; α-Synuclein