Effect of the Biphenyl Neolignan Honokiol on Aβ42-Induced Toxicity in Caenorhabditis elegans, Aβ42 Fibrillation, Cholinesterase Activity, DPPH Radicals, and Iron(II) Chelation

Kantham, Srinivas, Chan, Stephen, McColl, Gawain, Miles, Jared A., Veliyath, Suresh Kumar, Deora, Girdhar Singh, Dighe, Satish N., Khabbazi, Samira, Parat, Marie-Odile and Ross, Benjamin P. (2017) Effect of the Biphenyl Neolignan Honokiol on Aβ42-Induced Toxicity in Caenorhabditis elegans, Aβ42 Fibrillation, Cholinesterase Activity, DPPH Radicals, and Iron(II) Chelation. ACS Chemical Neuroscience, 8 9: 1901-1912. doi:10.1021/acschemneuro.7b00071


Author Kantham, Srinivas
Chan, Stephen
McColl, Gawain
Miles, Jared A.
Veliyath, Suresh Kumar
Deora, Girdhar Singh
Dighe, Satish N.
Khabbazi, Samira
Parat, Marie-Odile
Ross, Benjamin P.
Title Effect of the Biphenyl Neolignan Honokiol on Aβ42-Induced Toxicity in Caenorhabditis elegans, Aβ42 Fibrillation, Cholinesterase Activity, DPPH Radicals, and Iron(II) Chelation
Formatted title
Effect of the Biphenyl Neolignan Honokiol on Aβ42-Induced Toxicity in Caenorhabditis elegans, Aβ42 Fibrillation, Cholinesterase Activity, DPPH Radicals, and Iron(II) Chelation
Journal name ACS Chemical Neuroscience   Check publisher's open access policy
ISSN 1948-7193
Publication date 2017-09-01
Year available 2017
Sub-type Article (original research)
DOI 10.1021/acschemneuro.7b00071
Open Access Status Not yet assessed
Volume 8
Issue 9
Start page 1901
End page 1912
Total pages 12
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Subject 1314 Physiology
1303 Biochemistry
2805 Cognitive Neuroscience
1307 Cell Biology
Abstract The biphenyl neolignan honokiol is a neuroprotectant which has been proposed as a treatment for central nervous system disorders such as Alzheimer's disease (AD). The death of cholinergic neurons in AD is attributed to multiple factors, including accumulation and fibrillation of amyloid beta peptide (Aβ) within the brain; metal ion toxicity; and oxidative stress. In this study, we used a transgenic Caenorhabditis elegans model expressing full length Aβ as a convenient in vivo system for examining the effect of honokiol against Aβ-induced toxicity. Furthermore, honokiol was evaluated for its ability to inhibit Aβ oligomerization and fibrillation; inhibit acetylcholinesterase and butyrylcholinesterase; scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals; and chelate iron(II). Honokiol displayed activity similar to that of resveratrol and (-)-epigallocatechin gallate (EGCG) in delaying Aβ-induced paralysis in C. elegans, and it exhibited moderate-to-weak ability to inhibit Aβ on-pathway aggregation, inhibit cholinesterases, scavenge DPPH radicals, and chelate iron(II). Moreover, honokiol was found to be chemically stable relative to EGCG, which was highly unstable. Together with its good drug-likeness and brain availability, these results suggest that honokiol may be amenable to drug development and that the synthesis of honokiol analogues to optimize these properties should be considered.
Keyword Alzheimer's disease
Amyloid beta peptide
Caenorhabditis elegans
Cholinesterases
Honokiol
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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