Cited by 142Phytochemicals and Medicinal PlantsAlzheimer's disease research and treatmentsMedicinal Plants and Neuroprotection

Withanamides in Withania somnifera fruit protect PC‐12 cells from β‐amyloid responsible for Alzheimer's disease

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Jayaprakasam, Bolleddula, Padmanabhan, Kaillathe, Nair, Muraleedharan G.·2010·Phytotherapy Research

Abstract

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder with symptoms of confusion, memory loss, and mood swings. The beta-amyloid peptide, with 39-42 amino acid residues (BAP), plays a significant role in the development of AD. Although there is no cure for AD, it can be managed with available drugs to some degree. Several studies have revealed that natural antioxidants, such as vitamin E, vitamin C and beta-carotene, may help in scavenging free radicals generated during the initiation and progression of this disease. Therefore, there has been considerable interest in plant phytochemicals with antioxidant property as potential agents to prevent the progression of AD. Our earlier investigations of the Withania somnifera fruit afforded lipid peroxidation inhibitory withanamides that are more potent than the commercial antioxidants. In this study, we have tested two major withanamides A (WA) and C (WC) for their ability to protect the PC-12 cells, rat neuronal cells, from beta-amyloid induced cell damage. The cell death caused by beta-amyloid was negated by withanamide treatment. Molecular modeling studies showed that withanamides A and C uniquely bind to the active motif of beta-amyloid (25-35) and suggest that withanamides have the ability to prevent the fibril formation. Further understanding of the mechanism of action and in vivo efficacy of these withanamides may facilitate its development as a prophylaxis.

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Authors
Jayaprakasam, B., Padmanabhan, K., & Nair, M. G.
Affiliations
Michigan State University (US)
Corresponding author
Nair, Muraleedharan G.
Venue
Phytotherapy Research
Publisher
Wiley
Published
2010-05-26
Volume
24
Issue
6
Pages
859-863
ISSN
  • 0951-418X (ISSN-L)
  • 1099-1573
OpenAlex
W2020660605
Cited by
142
References
21
Citations by year
2026: 4 · 2025: 10 · 2024: 9 · 2023: 16 · 2022: 11 · 2021: 15 · 2020: 16 · 2019: 3 · 2018: 7 · 2017: 11 · 2016: 8 · 2015: 7 · 2014: 5 · 2013: 8 · 2012: 6
FWCI
9.78
Type
journal article
Language
en
Open access
Locations
  • Phytotherapy Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Michigan State University
  • College of Engineering, Michigan State University
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
Keywords
Withania somnifera, amyloid-beta, Alzheimer's disease, PC12 cells, neuroprotection, lipid peroxidation inhibition, antioxidant phytochemicals, amyloid fibril formation, molecular docking, neurodegeneration
MeSH terms
Alzheimer Disease, Amides, Animals, Cell Survival, Disaccharides, Fruit, Indoles, Models, Molecular, Peptide Fragments, Molecular Structure, Amyloid beta-Peptides, PC12 Cells, Withania, Rats

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