Characterization of β-secretase inhibitory extracts from sea cucumber (Stichopus japonicus) hydrolysis with their cellular level mechanism in SH-SY5Y cells
Abstract
Alzheimer’s disease (AD) is the main type of dementia found in the elderly population. The prevention of β-amyloid (Aβ) production by inhibiting β-secretase, which is required for Aβ generation, is the major focus of research in AD therapeutics. In this study, enzymatic extracts obtained from sea cucumber (Stichopus japonicus) hydrolysis were investigated for β-secretase inhibitory activities. Sea cucumber hydrolysates were prepared using various enzymes (Alcalase, α-chymotrypsin, Neutrase, papain, pepsin, and trypsin). Trypsin hydrolysate (IC₅₀, 93.59 ± 0.68 μg/ml) with the highest β-secretase inhibitory activity was separated into crude polysaccharide (TCP) and protein (TP) by ethanol precipitation. TCP (IC₅₀, 16.13 ± 1.15 μg/ml) exhibited higher β-secretase inhibitory activity than trypsin hydrolysate and TP (IC₅₀, 563.50 ± 25.18 μg/ml). Total sugar content in TCP was 11.58 ± 0.32 g/100 g. Major monosaccharides present in S. japonicus were arabinose, fucose, galactose, mannose and ramnose at 1.76 mg/g, 11.98 mg/g, 1.33 mg/g and 0.1 mg/g, respectively. Sulfate and uronic acid contents were 5.69 ± 0.15 g/100 g and 0.49 ± 0.01 g/100 g. Cytotoxicity of TCP different concentrations were tested in SH-SY5Y cells using MTT assay. Treated concentrations at 1, 5, 10, 30, 50, and 100 µg/ml concentrations were not toxic at cellular level. Further, quantitative protein expression reduction of BACE, sAPPβ, β-amyloid, p-JNK, and p-p38 in SH-SY5Y cells were confirmed by Western blot analysis. Therefore, results of this study suggest the potential application of S. japonicus in food and biomedicine industries.
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Aβ peptide production is regulated through enzyme inhibition associated with the amyloidogenic cascade, mainly β-secretase.
“Recent reports point to the Aβ peptides production regulation, through enzyme inhibition associated with the amyloidogenic cascade, mainly β-secretase [162,163,164].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [163]
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- Authors
- Ma, E.-H., Rathnayake, A. U., Lee, J. K., Lee, S.-M., & Byun, H.-G.
- Affiliations
- Gangneung–Wonju National University (KR)
- Corresponding author
- Byun, Hee-Guk
- Venue
- European Food Research and Technology
- Published
- 2021-06-10
- Volume
- 247
- Issue
- 8
- Pages
- 2039-2052
- ISSN
- 0373-0174 (ISSN-L)
- 1438-2377
- 1438-2385
- OpenAlex
- W3171403924
- Cited by
- 8
- References
- 48
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 1
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- European Food Research and Technology (publishedVersion)
- Funders
- Korea Institute of Marine Science and Technology promotion (20140441)
- Ministry of Oceans and Fisheries
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Hydrolysis and Bioactive Peptides
- Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Echinoderm biology and ecology
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- beta-secretase inhibition, Apostichopus japonicus, trypsin hydrolysate, polysaccharides, Alzheimer's disease, amyloid-beta, BACE, SH-SY5Y cells, monosaccharide composition, uronic acid, cytotoxicity, marine bioactive peptides
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