title: Rutin inhibits β-amyloid aggregation and cytotoxicity, attenuates oxidative stress, and decreases the production of nitric oxide and proinflammatory cytokines.
abstract: Alzheimer's disease (AD) is a complex, multi-factorial neurodegenerative disease. The aggregation of soluble β-amyloid (Aβ) into fibrillar deposits is a pathological hallmark of AD. The Aβ aggregate-induced neurotoxicity, inflammatory reactions, oxidative stress, and nitric oxide (NO) generation are strongly linked to the etiology of AD. Here, we show that the common dietary flavonoid, rutin, can dose-dependently inhibit Aβ42 fibrillization and attenuate Aβ42-induced cytotoxicity in SH-SY5Y neuroblastoma cells. Moreover, rutin decreases the formation of reactive oxygen species (ROS), NO, glutathione disulfide (GSSG), and malondialdehyde (MDA), reduces inducible nitric oxide synthase (iNOS) activity, attenuates mitochondrial damage, increases the glutathione (GSH)/GSSG ratio, enhances the activities of super oxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and modulates the production of proinflammatory cytokines by decreasing TNF-α and IL-1β generation in microglia. Taken together, the actions of rutin on multiple pathogenic factors deserves further investigation for the prevention and treatment of AD.
authors.affiliation: Tsinghua University School of Medicine, Haidian District, Beijing 100084, China.
authors.forename: Shao-wei
authors.initials: SW
authors.lastname: Wang
authors.forename: Yu-Jiong
authors.initials: YJ
authors.lastname: Wang
authors.forename: Ya-jing
authors.initials: YJ
authors.lastname: Su
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Zhou
authors.forename: Shi-gao
authors.initials: SG
authors.lastname: Yang
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Ya-nan
authors.initials: YN
authors.lastname: Li
authors.forename: Zi-ping
authors.initials: ZP
authors.lastname: Zhang
authors.forename: Da-wei
authors.initials: DW
authors.lastname: Zhan
authors.forename: Rui-tian
authors.initials: RT
authors.lastname: Liu
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012431:Rutin / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D009569:Nitric Oxide; D008315:Malondialdehyde; D012431:Rutin; D002374:Catalase; D005979:Glutathione Peroxidase; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D005978:Glutathione