Abstract
Neuroprotective and neurotrophic supports are critical for neuronal survival, outgrowth, and functional activity in the degenerating brain where oxidative stress is a leading cause of neurological disorders. An ethanol extract of the phaeophyte Undaria pinnatifida (UPE) concentration dependently increased the viability of rat hippocampal neurons in both hypoxia-induced oxidative stress and normoxic conditions. UPE, at an optimal 15 μg mL−1, significantly reduced reactive oxygen species formation, DNA fragmentation, early and late apoptosis rates, and mitochondrial membrane dysfunction against hypoxia. In addition, the most active neuroprotectant from UPE was identified as fucoxanthin (Fx) by reverse-phase high-pressure liquid chromatography (RP-HPLC) and 1H NMR. Fucoxanthinol (FxOH), a metabolite after enzymatic hydrolysis of Fx, significantly provided protection from neurite breakage and also enhanced the length of neurites in hypoxia cultures. The findings suggest that UPE and its active component Fx as well as FxOH have the ability to protect central nervous system neurons through anti-excitatory and anti-oxidative actions.
Similar content being viewed by others
References
Ali TB, Schleret TR, Reilly BM, Chen WY, Abagyan R (2015) Adverse effects of cholinesterase inhibitors in dementia, according to the pharmacovigilance databases of the United-States and Canada. PLoS One 10:e0144337
Asai A, Yonekura L, Nagao A (2008) Low bioavailability of dietary epoxyxanthophylls in humans. Br J Nutr 100:273–277
Bhuiyan MMH, Mohibbullah M, Hannan MA, Hong YK, Choi JS, Choi IS, Moon IS (2015) Undaria pinnatifida promotes spinogenesis and synaptogenesis and potentiates functional presynaptic plasticity in hippocampal neurons. Am J Chin Med 43:529–542
Dembitsky VM, Maoka T (2007) Allenic and cumulenic lipids. Prog Lipid Res 46:328–375
Donguibogam Committee (1999) Translated Donguibogam. Bubin-munwha Press, Seoul
Fung A, Hamid N, Lu J (2013) Fucoxanthin content and antioxidant properties of Undaria pinnatifida. Food Chem 136:1055–1062
Goslin K, Asmussen H, Banker G (1998) Rat hippocampal neurons in low-density culture. In: Banker G, Goslin K (eds) Culturing nerve cells, 2nd edn. MIT Press, Massachusetts, pp 339–370
Hannan MA, Mohibbullah M, Hwang SY, Lee K, Kim YC, Hong YK, Moon IS (2014) Differential neuritogenic activities of two edible brown macroalgae, Undaria pinnatifida and Saccharina japonica. Am J Chin Med 42:1371–1384
Hashimoto T, Ozaki Y, Taminato M, Das SK, Mizuno M, Yoshimura K, Kanazawa K (2009) The distribution and accumulation of fucoxanthin and its metabolites after oral administration in mice. Br J Nutr 102:242–248
Higuchi Y (2003) Chromosomal DNA fragmentation in apoptosis and necrosis induced by oxidative stress. Biochem Pharmacol 66:1527–1535
Khan MNA, Lee MC, Kang JY, Park NG, Fujii H, Hong YK (2008) Effects of the brown seaweed Undaria pinnatifida on erythematous inflammation assessed using digital photo analysis. Phytother Res 22:634–639
Khan MNA, Yoon SJ, Choi JS, Park NG, Lee HH, Cho JY, Hong YK (2009) Anti-edema effects of brown seaweed (Undaria pinnatifida) extract on phorbol 12-myristate 13-acetate-induced mouse ear inflammation. Am J Chin Med 37:373–381
Korea Fisheries Association (2016) Korean fisheries yearbook. Uno Design Press, Seoul
Lemasters JJ, Qian T, Bradham CA, Brenner DA, Cascio WE, Trost LC, Herman B (1999) Mitochondrial dysfunction in the pathogenesis of necrotic and apoptotic cell death. J Bioenerg Biomembr 31:305–319
Lin J, Huang L, Yu J, Xiang S, Wang J, Zhang J, Wang Q (2016) Fucoxanthin, a marine carotenoid, reverses scopolamine-induced cognitive impairments in mice and inhibits acetylcholinesterase in vitro. Mar Drugs 14:67–83
Liu DS, Zhou YH, Liang ES, Li W, Lin WW, Chen FF, Gao W (2013) Neuroprotective effects of the Chinese Yi-Qi-Bu-Shen recipe extract on injury of rat hippocampal neurons induced by hypoxia/reoxygenation. J Ethnopharmacol 145:168–174
Mohibbullah M, Hannan MA, Choi JY, Bhuiyan MMH, Hong YK, Choi JS, Moon IS (2015) The edible marine alga Gracilariopsis chorda alleviates hypoxia/reoxygenation-induced oxidative stress in cultured hippocampal neurons. J Med Food 18:960–971
Mok IK, Yoon JR, Pan CH, Kim SM (2016) Development, quantification, method validation, and stability study of a novel fucoxanthin-fortified milk. J Agric Food Chem 64:6196–6202
Moon IS, Cho S, Jin I, Walikonis R (2007) A simple method for combined fluorescence in situ hybridization and immunocytochemistry. Mol Cells 24:76–82
Mori K, Ooi T, Hiraoka M, Oka N, Hamada H, Tamura M, Kusumi T (2004) Fucoxanthin and its metabolites in edible brown algae cultivated in deep seawater. Mar Drugs 2:63–72
Nicolle MM, Gonzalez J, Sugaya K, Baskerville KA, Bryan D, Lund K, McKinney M (2001) Signatures of hippocampal oxidative stress in aged spatial learning-impaired rodents. Neuroscience 107:415–431
Nishibori N, Itoh M, Kashiwagi M, Arimochi H, Morita K (2012) In vitro cytotoxic effect of ethanol extract prepared from sporophyll of Undaria pinnatifida on human colorectal cancer cells. Phytother Res 26:191–196
Peng J, Yuan JP, Wu CF, Wang JH (2011) Fucoxanthin, a marine carotenoid present in brown seaweeds and diatoms: metabolism and bioactivities relevant to human health. Mar Drugs 9:1806–1828
Rajauria G, Foley B, Abu-Ghannam N (2017) Characterization of dietary fucoxanthin from Himanthalia elongata brown seaweed. Food Res Int 99:995–1001
Rogakou EP, Nieves-Neira W, Boon C, Pommier Y, Bonner WM (2000) Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J Biol Chem 275:9390–9395
Suski JM, Lebiedzinska M, Bonora M, Pinton P, Duszynski J, Wieckowski MR (2012) Relation between mitochondrial membrane potential and ROS formation. Meth Mol Biol 810:183–205
Tavakkoli M, Miri R, Jassbi AR, Erfani N, Asadollahi M, Ghasemi M, Firuzi O (2014) Carthamus, Salvia and Stachys species protect neuronal cells against oxidative stress induced apoptosis. Pharm Biol 52:1550–1557
Terasaki M, Hirose A, Narayan B, Baba Y, Kawagoe C, Yasui H, Miyashita K (2009) Evaluation of recoverable functional lipid components of several brown seaweeds (phaeophyta) from Japan with special reference to fucoxanthin and fucosterol contents. J Phycol 45:974–980
Uttara B, Singh AV, Zamboni P, Mahajan RT (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7:65–74
Xin Z, Shiping Z, Chunna A, Hongning Z, Yi S, Yanmei L, Xiaoping P (2015) Neuroprotective effect of fucoxanthin on β-amyloid-induced cell death. J Chin Pharm Sci 24:467–474
Yamamoto K, Ishikawa C, Katano H, Yasumoto T, Mori N (2011) Fucoxanthin and its deacetylated product, fucoxanthinol, induce apoptosis of primary effusion lymphomas. Cancer Lett 300:225–234
Yu J, Lin JJ, Yu R, He S, Wang QW, Cui W, Zhang JR (2017) Fucoxanthin prevents H2O2-induced neuronal apoptosis via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway. Food Nutr Res 61:1304678
Zhang H, Pang Z, Han C (2014) Undaria pinnatifida (Wakame): a seaweed with pharmacological properties. Sci Int 2:32−36
Funding
This work was supported by a research grant from Pukyong National University (Year 2017).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
All animal care and use were in accordance with the institutional guidelines and approved by the Institutional Animal Care and Use Committee of the College of Medicine, Dongguk University, Republic of Korea.
Rights and permissions
About this article
Cite this article
Mohibbullah, M., Haque, M.N., Khan, M.N.A. et al. Neuroprotective effects of fucoxanthin and its derivative fucoxanthinol from the phaeophyte Undaria pinnatifida attenuate oxidative stress in hippocampal neurons. J Appl Phycol 30, 3243–3252 (2018). https://doi.org/10.1007/s10811-018-1458-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10811-018-1458-6