ArticleACS chemical neuroscience2016
C-Glycosylflavones Alleviate Tau Phosphorylation and Amyloid Neurotoxicity through GSK3β Inhibition.
Article in ACS chemical neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 61 citations in OpenAlex.
- Isoorientin inhibits oxidative stress to ameliorate cognitive dysfunction in type 2 diabetes mice via GSK3β/Nrf2 axis.Metabolic brain disease · 2026Article
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
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- The dual role of glycogen synthase kinase-3 beta (GSK3β) in neurodegenerative pathologies: interplay between autophagy and disease progression.Frontiers in pharmacology · 2025Review
- GSK3: A potential target and pending issues for treatment of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Review
- The Neuroprotective Flavonoids Sterubin and Fisetin Maintain Mitochondrial Health under Oxytotic/Ferroptotic Stress and Improve Bioenergetic Efficiency in HT22 Neuronal Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Neurotrophic Natural Products.Progress in the chemistry of organic natural products · 2024Article
- Article
- Integrated metabolite analysis and health-relevantFrontiers in nutrition · 2023Article
- The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation.Frontiers in cellular neuroscience · 2023Review
- Interactions between Major Bioactive Polyphenols of Sugarcane Top: Effects on Human Neural Stem Cell Differentiation and Astrocytic Maturation.International journal of molecular sciences · 2022Article
- Cannabinol inhibits oxytosis/ferroptosis by directly targeting mitochondria independently of cannabinoid receptors.Free radical biology & medicine · 2022Article
- Natural Products in the Prevention of Metabolic Diseases: Lessons Learned from the 20th KAST Frontier Scientists Workshop.Nutrients · 2021Review
- Natural products targeting mitochondria: emerging therapeutics for age-associated neurological disorders.Pharmacology & therapeutics · 2021Review
- Dietary Anti-Aging Polyphenols and Potential Mechanisms.Antioxidants (Basel, Switzerland) · 2021Review
- Computer-Aided Drug Design of β-Secretase, γ-Secretase and Anti-Tau Inhibitors for the Discovery of Novel Alzheimer's Therapeutics.International journal of molecular sciences · 2020Review
- Sugarcane (Frontiers in cell and developmental biology · 2020Article
- Isoorientin Inhibits Inflammation in Macrophages and Endotoxemia Mice by Regulating Glycogen Synthase Kinase 3Mediators of inflammation · 2020Article
- 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) Urea, a Selective and Potent Dual Inhibitor of Soluble Epoxide Hydrolase and p38 Kinase Intervenes in Alzheimer's Signaling in Human Nerve Cells.ACS chemical neuroscience · 2019Article
- Discovery of Selective, Substrate-Competitive, and Passive Membrane Permeable Glycogen Synthase Kinase-3β Inhibitors: Synthesis, Biological Evaluation, and Molecular Modeling of New C-Glycosylflavones.ACS chemical neuroscience · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is the most common brain disorder worldwide. Aberrant tau hyperphosphorylation and accumulation play critical roles in the formation of neurofibrillary tangles highly associated with neuronal dysfunction and cognitive impairment in AD pathogenesis. Glycogen synthase kinase-3β (GSK3β) is a key kinase responsible for tau hyperphosphorylation. Selective inhibition of GSK3β is a promising strategy in AD therapy. Corn silks (CS, Zea mays L.) have been traditionally used as a medicinal herb and recently noted for their potentially cognitive benefits. However, the neuroprotective components of CS and their molecular mechanism have received little attention to date. As part of our effort screening phytochemicals against a broad panel of kinases targeting AD tauopathy, we found inhibition of GSK3β by CS extracts. Subsequent bioassay-guided fractionation led to the isolation and identification of two 6-C-glycosylflavones, isoorientin (1) and 3'-methoxymaysin (2), with selective inhibition against GSK3β in vitro. Enzyme kinetics and molecular docking studies demonstrated that 1 specifically inhibited GSK3β via an ATP noncompetitive mechanism, acting as a substrate competitive inhibitor of GSK3β. Further in vitro cellular studies demonstrated that 1 effectively attenuated tau phosphorylation mediated by GSK3β and was neuroprotective against β-amyloid-induced tau hyperphosphorylation and neurotoxicity in SH-SY5Y cells. The C-glycosylflavones represent new lead candidates with a novel mechanism of action for the development of AD phytopharmaceuticals.
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