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Cited by 38Alzheimer's disease research and treatmentsMedicinal Plants and NeuroprotectionCholinesterase and Neurodegenerative Diseases

Medicinal value of asiaticoside for Alzheimer’s disease as assessed using single-molecule-detection fluorescence correlation spectroscopy, laser-scanning microscopy, transmission electron microscopy, and in silico docking

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Shahdat Hossain, Michio Hashimoto, Masanori Katakura, Abdullah Al Mamun, Osamu Shido·2015·BMC Complementary and Alternative Medicine
DOI 10.1186/s12906-015-0620-9PMC PMC4422550
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Abstract

BACKGROUND: Identifying agents that inhibit amyloid beta peptide (Aβ) aggregation is the ultimate goal for slowing Alzheimer's disease (AD) progression. This study investigated whether the glycoside asiaticoside inhibits Aβ1-42 fibrillation in vitro. METHODS: Fluorescence correlation spectroscopy (FCS), evaluating the Brownian diffusion times of moving particles in a small confocal volume at the single-molecule level, was used. If asiaticoside inhibits early Aβ1-42 fibrillation steps, more Aβs would remain free and rapidly diffuse in the confocal volume. In contrast, "weaker or no inhibition" permits a greater number of Aβs to polymerize into oligomers, leading to fibers and gives rise to slow diffusion times in the solution. Trace amounts of 5-carboxytetramethylrhodamine (TAMRA)-labeled Aβ1-42 in the presence of excess unlabeled Aβ1-42 (10 μM) was used as a fluorescent probe. Steady-state and kinetic-Thioflavin T (ThT) fluorospectroscopy, laser-scanning fluorescence microscopy (LSM), and transmission electron microscopy (TEM) were also used to monitor fibrillation. Binding of asiaticoside with Aβ1-42 at the atomic level was computationally examined using the Molegro Virtual Docker and PatchDock. RESULTS: With 1 h of incubation time for aggregation, FCS data analysis revealed that the diffusion time of TAMRA-Aβ1-42 was 208 ± 4 μs, which decreased to 164 ± 8.0 μs in the presence of asiaticoside, clearly indicating that asiaticoside inhibited the early stages Aβ1-42 of fibrillation, leaving more free Aβs in the solution and permitting their rapid diffusion in the confocal volume. The inhibitory effects were also evidenced by reduced fiber formation as assessed by steady-state and kinetic ThT fluorospectroscopy, LSM, and TEM. Asiaticoside elongated the lag phase of Aβ1-42 fibrillation, indicating the formation of smaller amyloid species were impaired in the presence of asiaticoside. Molecular docking revealed that asiaticoside binds with amyloid intra- and inter-molecular amino acid residues, which are responsible for β-sheet formation and longitudinal extension of fibrils. CONCLUSION: Finally, asiaticoside prevents amyloidogenesis that precedes neurodegeneration in patients with Alzheimer's disease.

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  • Madecassoside and asiaticoside are incorporated into the treatment of various neurodegenerative disorders like Alzheimer's and Parkinson's diseases.

    “and are incorporated into the treatment of various neurodegenerative disorders like Alzheimer's and Parkinson's diseases. 33 , 34”

    From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [33]

    The Discussion (page unavailable) links both compounds to Alzheimer’s-related research: it reports improved memory in AD-model rats given madecassoside and inhibition of Aβ fibrillation by asiaticoside. The Conclusions (page unavailable) recommend further development of asiaticoside for clinical use, not that either compound is already incorporated into treatment. The passages do not address Parkinson’s disease. (LLM, conf=0.88)

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  • Madecassoside inhibits Aβ1-42 fibrillation and improves memory loss in AD model rats.

    “In addition, a previous study by the same team has also accounted for the role of madecassoside in inhibiting Aβ1–42 fibrillation as well as improving memory loss of AD model rats. 33”

    From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [33]

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Cited by

Sorted by citations

Authors
Hossain, S., Hashimoto, M., Katakura, M., Mamun, A. A., & Shido, O.
Affiliations
Shimane University (JP)
Corresponding author
Michio Hashimoto
ORCID
Venue
BMC Complementary and Alternative Medicine
Publisher
Springer Science and Business Media LLC
Published
2015-04-14
Volume
15
Issue
1
Pages
118-118
ISSN
1472-6882 (ISSN-L)
DOI
10.1186/s12906-015-0620-9
PMC
PMC4422550
OpenAlex
W2018644003
Cited by
38
References
3
Citations by year
2025: 5 · 2024: 2 · 2023: 6 · 2022: 5 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 3
FWCI
2.70
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Complementary and Alternative Medicine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Shimane University
  • Japan Society for the Promotion of Science (26350120)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
asiaticoside, Alzheimer's disease, amyloid-beta 42, amyloid fibrillation inhibition, single-molecule diffusion, thioflavin T, molecular docking, ligand binding, glycosides, lag phase, β-sheet formation, anti-amyloid agents, natural products, medicinal plants, Withania somnifera
MeSH terms
Alzheimer Disease, Amyloid, Fluorescence, Humans, Phytotherapy, Microscopy, Peptide Fragments, Plant Extracts, Rhodamines, Spectrum Analysis, Triterpenes, Amyloid beta-Peptides, Centella, Molecular Docking Simulation

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