Rutin inhibits β-amyloid aggregation and cytotoxicity, attenuates oxidative stress, and decreases the production of nitric oxide and proinflammatory cytokines

Shao-wei Wang; Yu-Jiong Wang; Ya-jing Su; Wei-wei Zhou; Shi-gao Yang; Ran Zhang; Min Zhao; Ya-nan Li; Zi-ping Zhang; Da-wei Zhan; Rui-tian Liu

doi:10.1016/j.neuro.2012.03.003

Rutin inhibits β-amyloid aggregation and cytotoxicity, attenuates oxidative stress, and decreases the production of nitric oxide and proinflammatory cytokines

Neurotoxicology. 2012 Jun;33(3):482-90. doi: 10.1016/j.neuro.2012.03.003. Epub 2012 Mar 15.

Authors

Shao-wei Wang¹, Yu-Jiong Wang, Ya-jing Su, Wei-wei Zhou, Shi-gao Yang, Ran Zhang, Min Zhao, Ya-nan Li, Zi-ping Zhang, Da-wei Zhan, Rui-tian Liu

Affiliation

¹ Tsinghua University School of Medicine, Haidian District, Beijing 100084, China.

PMID: 22445961
DOI: 10.1016/j.neuro.2012.03.003

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid beta-Peptides / metabolism*
Anti-Inflammatory Agents / pharmacology*
Antioxidants / pharmacology*
Catalase / metabolism
Cell Line, Tumor
Cytokines / metabolism*
Cytoprotection
Dose-Response Relationship, Drug
Down-Regulation
Glutathione / metabolism
Glutathione Peroxidase / metabolism
Humans
Inflammation Mediators / metabolism*
Interleukin-1beta / metabolism
Malondialdehyde / metabolism
Mitochondria / drug effects
Mitochondria / metabolism
Mitochondria / pathology
Neurons / drug effects*
Neurons / immunology
Neurons / metabolism
Neurons / pathology
Neuroprotective Agents / pharmacology*
Nitric Oxide / metabolism*
Nitric Oxide Synthase Type II / metabolism
Oxidative Stress / drug effects*
Peptide Fragments / metabolism*
Reactive Oxygen Species / metabolism
Rutin / pharmacology*
Superoxide Dismutase / metabolism
Time Factors
Tumor Necrosis Factor-alpha / metabolism

Substances

Amyloid beta-Peptides
Anti-Inflammatory Agents
Antioxidants
Cytokines
Inflammation Mediators
Interleukin-1beta
Neuroprotective Agents
Peptide Fragments
Reactive Oxygen Species
Tumor Necrosis Factor-alpha
amyloid beta-protein (1-42)
Nitric Oxide
Malondialdehyde
Rutin
Catalase
Glutathione Peroxidase
NOS2 protein, human
Nitric Oxide Synthase Type II
Superoxide Dismutase
Glutathione