A novel BACE inhibitor isolated from Eisenia bicyclis exhibits neuroprotective activity against β-amyloid toxicity
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Alzheimer’s disease (AD) is a disturbing and advanced neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau proteins in the brain. The deposition of Aβ aggregates triggers synaptic dysfunction, and neurodegeneration, which lead to cognitive disorders. Here, we found that FF isolated from an eatable perennial brown seaweed E.bicyclis protect against Aβ-induced neurotoxicity in neuroblastoma cells stably transfected with two amyloid precursor protein (APP) constructs: the APP695 cDNA (SH-SY5Y-APP695swe). The FF demonstrated strong inhibitory activity for β-secretase (IC50 16.1 μM) and its inhibition pattern was investigated using Lineweaver-Burk and Dixon plots, and found to be non-competitive. Then, we tested whether FF could inhibit production of Aβ in SH-SY5Y-APP695swe. FF inhibited the production of Aβ and soluble-APP, residue of APP from cleaved APP by β-secretase. Our data show that FF can inhibit the production of Aβ and soluble-APPβ via inhibition of β-secretase activity. Taken together these results suggest that FF may be worthy of future study as an anti-AD treatment.
Abstract
Alzheimer’s disease (AD) is a disturbing and advanced neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau proteins in the brain. The deposition of Aβ aggregates triggers synaptic dysfunction, and neurodegeneration, which lead to cognitive disorders. Here, we found that FF isolated from an eatable perennial brown seaweed E.bicyclis protect against Aβ-induced neurotoxicity in neuroblastoma cells stably transfected with two amyloid precursor protein (APP) constructs: the APP695 cDNA (SH-SY5Y-APP695swe). The FF demonstrated strong inhibitory activity for β-secretase (IC50 16.1 μM) and its inhibition pattern was investigated using Lineweaver-Burk and Dixon plots, and found to be non-competitive. Then, we tested whether FF could inhibit production of Aβ in SH-SY5Y-APP695swe. FF inhibited the production of Aβ and soluble-APP, residue of APP from cleaved APP by β-secretase. Our data show that FF can inhibit the production of Aβ and soluble-APPβ via inhibition of β-secretase activity. Taken together these results suggest that FF may be worthy of future study as an anti-AD treatment.
참고문헌 (28)
- Artan M, "Anti-HIV-1 activity of phloroglucinol derivative, 6, 6′-bieckol. from Ecklonia cava", Bioorgan Med Chem, 16, pp.7921~7926 (2008)
- Athukorala Y, "Anticoagulant activity of marine green and brown algae collected from Jeju Island in Korea", Bioresour Technol, 98, pp.1711~1716 (2007)
- Burtin P, "Nutritional value of seaweeds", EJEAFChe, 2, pp.498~503 (2003)
- Cornish-Bowden A, "Statistical considerations in the estimation of enzyme kinetic parameters by the direct plot and other methods", Biochem J, 139, pp.721~730 (1974)
- Crouch PJ, "Mechanisms of Aβ mediated neurodegeneration in Alzheimer’s disease", Int J Biochem Cell Biol, 40, pp.181~198 (2008)
- Durrenberger PF, "Selection of novel reference genesfor use in the human central nervous system : a BrainNet Europe Study", Acta Neuropathol, 124, pp.893~903 (2012)
- Ghosh AK, "Developing β-secretase inhibitors for treatment of Alzheimer’s disease", J Neurochem, 120, pp.71~83 (2012)
- Glombitza KW, "Phlorotannins with dibenzodioxin structural elements from the brown alga Eisenia arborea", Phytochemistry, 24, pp.543~551 (1985)
- Heo SJ, "Antioxidant activities of enzymatic extracts from brown seaweeds", Bioresour Technol, 96, pp.1613~1623 (2005)
- Jämsä A, "BACE-1 inhibition prevents the γ-secretase inhibitor evoked Aβ rise in human neuroblastoma SH-SY5Y cells", J Biomed Sci, 18, pp.76~ (2011)
- Johnston JA, "Platelet β-secretase activity is increased in Alzheimer’ disease", Neurobiol Agin, 29, pp.661~668 (2008)
- Jung HA, "Molecular docking studies of phlorotannins from Eisenia bicyclis with BACE1 inhibitory activity", Bioorg Med Chem Lett, 20, pp.3211~3215 (2010)
- Kang HS, "A new phlorotannin from the brown alga Ecklonia stolonifera", Chem Pharm Bull, 51, pp.1012~1014 (2003)
- Sher Bahadar Khan, "Protective Effect of Amphiroa dilatata on ROS Induced Oxidative Damage and MMP Expressions in HT1080 Cells", Biotechnology and Bioprocess Engineering, 15(1), pp.191~198 (2010), 한국생물공학회
- Kim MM, "Anti-inflammatory effect of Ishige okamurae ethanolic extract via inhibition of NF-κB transcription factor in RAW 2647cells", Phytother Res, 23, pp.628~634 (2009)
- Kong CS, "Induction of apoptosis by phloroglucinol derivative from Ecklonia cava in MCF-7 human breast cancer cells", Food Chem Toxicol, 47, pp.1653~1658 (2009)
- Kousaka K, "Novel oxylipin metabolites from the brown alga Eisenia bicyclis", J Nat Prod, 66, pp.1318~1323 (2003)
- Kurata K, "C26 sterol from the brown alga Eisenia bicyclis", Phytochemistry, 29, pp.3678~3680 (1990)
- Li Y, "Anti-allergic effects of phlorotannins on histamine release via binding inhibition between IgE and FcεRI", J Agr Food Chem, 56, pp.12073~12080 (2008)
- Masters CL, "Biochemistry of amyloid β-protein and amyloid deposits in Alzheimer disease", Cold Spring Harb Perspect Med, 2, pp.a006262~ (2012)
- Murphy MP, "Alzheimer's disease and the amyloid-beta peptide", J Alzheimers Dis, 19, pp.311~323 (2010)
- Noda H, "Studies on the antitumor activity of marine algae", Bull Jpn Soc Sci Fish, 55, pp.1254~1264 (1989)
- Okada Y, "A new phloroglucinol derivatives from the brown alga Eisenia bicyclis : potential for the effective treatment of diabetic complications", J Nat Prod, 67, pp.103~105 (2004)
- Ragan MA, "Phlorotannins, brown algal polyphenols", Prog Phycol Res, 4, pp.177~241 (1986)
- Ryu JK, "Minocycline inhibits neuronal death and glial activation induced by β-amyloid peptide in rat hippocampus", Glia, 48, pp.85~90 (2004)
- 신현철, "An Antioxidative and Antiinflammatory Agent for Potential Treatment of Osteoarthritis from Ecklonia cava", Archives of Pharmacal Research, 29(2), pp.165~171 (2006), 대한약학회
- Šimić G, "Tau protein hyperphosphorylation and aggregation in Alzheimer’s disease and other tauopathies, and possible neuroprotective strategies", Biomolecules, 6, pp.6~ (2016)
- Zarros A, "In which cases is neuroprotection useful", Adv Altern Think Neurosci, 1, pp.3~5 (2009)