title: Rutin inhibits amylin-induced neurocytotoxicity and oxidative stress.
abstract: Recent evidence showed that amylin deposition is not only found in the pancreas in type 2 diabetes mellitus (T2DM) patients, but also in other peripheral organs, such as kidneys, heart and brain. Circulating amylin oligomers that cross the blood-brain barrier and accumulate in the brain may be an important contributor to diabetic cerebral injury and neurodegeneration. Moreover, increasing epidemiological studies indicate that there is a significant association between T2DM and Alzheimer's disease (AD). Amylin and β-amyloid (Aβ) may share common pathophysiology and show strikingly similar neurotoxicity profiles in the brain. To explore the potential effects of rutin on AD, we here investigated the effect of rutin on amylin aggregation by thioflavin T dyeing, evaluated the effect of rutin on amylin-induced neurocytotoxicity by the MTT assay, and assessed oxidative stress, as well as the generation of nitric oxide (NO) and pro-inflammatory cytokines in neuronal cells. Our results showed that the flavonoid antioxidant rutin inhibited amylin-induced neurocytotoxicity, decreased the production of reactive oxygen species (ROS), NO, glutathione disulfide (GSSG), malondialdehyde (MDA) and pro-inflammatory cytokines TNF-α and IL-1β, attenuated mitochondrial damage and increased the GSH/GSSG ratio. These protective effects of rutin may have resulted from its ability to inhibit amylin aggregation, enhance the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and reduce inducible nitric oxide synthase (iNOS) activity. These in vitro results indicate that rutin is a promising natural product for protecting neuronal cells from amylin-induced neurotoxicity and oxidative stress, and rutin administration could be a feasible therapeutic strategy for preventing AD development and protecting the aging brain or slowing neurodegenerative processes.
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. rtliu@ipe.ac.cn.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Yu
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Li
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Su
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Zhou
authors.forename: Zi-Ping
authors.initials: ZP
authors.lastname: Zhang
authors.forename: Shao-Wei
authors.initials: SW
authors.lastname: Wang
authors.forename: Peng-Xin
authors.initials: PX
authors.lastname: Xu
authors.forename: Yu-Jiong
authors.initials: YJ
authors.lastname: Wang
authors.forename: Rui-Tian
authors.initials: RT
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000975:Antioxidants / Q000494:pharmacology; D001812:Blood-Brain Barrier; D002374:Catalase / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D058228:Islet Amyloid Polypeptide / Q000633:toxicity*; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012431:Rutin / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D053583:Interleukin-1beta; D058228:Islet Amyloid Polypeptide; D020011:Protective Agents; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; 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; D019803:Glutathione Disulfide