No CrossRef data available.
Article contents
Oral supplementation of fucoxanthin regulates gene expression in the brain of middle-aged rats
Published online by Cambridge University Press: 03 September 2025
Abstract
Age is the main risk factor for many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and frontotemporal dementia. Despite our limited understanding of cellular mechanisms of ageing-associated neuronal loss, an increasing number of studies demonstrate that oxidative stress and inflammation are key drivers. Epidemiological studies indicate that diet during middle adulthood can influence the risk of developing neurodegenerative diseases later in life, so it is important to investigate dietary interventions to combat oxidative stress and inflammation. In this study, we hypothesised that treatment with fucoxanthin, a marine carotenoid with strong antioxidant properties, prevents ageing-associated oxidative stress that is known to be related to natural brain ageing. Treatment with fucoxanthin protected rat primary hippocampal neurons against oxidative stress and ageing in vitro. In our in vivo study, middle-aged male Sprague-Dawley rats were gavaged with fucoxanthin (1 mg/kg, 5 d/week, n 6) or vehicle (n 6) for 4 weeks. After supplementation was completed, brain samples were harvested and subjected to quantitative and bioinformatic analyses. Fucoxanthin was detected and shown to decrease lipid peroxidation in the brains of the animals supplemented with fucoxanthin. Microarray analysis showed that treatment with fucoxanthin changed 5602 genes. Together, our results suggest that treatment with fucoxanthin prevents ageing-associated oxidative stress and is capable of regulating genes that potentially ameliorate age-related changes to the brain.
Information
- Type
- Research Article
- Information
- Copyright
- © The Author(s), 2025. Published by Cambridge University Press on behalf of the Nutrition Society
References
Hou, Y, Dan, X, Babbar, M, et al. (2019) Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 15, 565–581.CrossRefGoogle ScholarPubMed
Dement, A (2024) 2024 Alzheimer’s disease facts and figures. Alzheimers Dement 20, 3708–3821.Google Scholar
Willis, AW, Roberts, E, Beck, JC, et al. (2022) Incidence of Parkinson disease in North America. NPJ Parkinsons Dis 8, 170.CrossRefGoogle ScholarPubMed
WHO (2022) Launch of WHO’s Parkinson Disease Technical Brief. ––https://www.who.int/news/item/14–06–2022-launch-of-who-s-parkinson-disease-technical-brief (accessed June 2022).Google Scholar
Collaborators GBDN (2019) Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 18, 459–480.10.1016/S1474-4422(18)30499-XCrossRefGoogle Scholar
Alwahsh, SM & Gebhardt, R (2017) Dietary fructose as a risk factor for non-alcoholic fatty liver disease (NAFLD). Arch Toxicol 91, 1545–1563.10.1007/s00204-016-1892-7CrossRefGoogle ScholarPubMed
Alwahsh, SM, Xu, M, Schultze, FC, et al. (2014) Combination of alcohol and fructose exacerbates metabolic imbalance in terms of hepatic damage, dyslipidemia, and insulin resistance in rats. PLoS One 9, e104220.CrossRefGoogle ScholarPubMed
Song, BJ, Akbar, M, Abdelmegeed, MA, et al. (2014) Mitochondrial dysfunction and tissue injury by alcohol, high fat, nonalcoholic substances and pathological conditions through post-translational protein modifications. Redox Biol 3, 109–123.10.1016/j.redox.2014.10.004CrossRefGoogle ScholarPubMed
Ferdous, KA, Sarihi, S, Ellis, AC, et al. (2023) Neuroprotective potential of brown seaweed phytochemicals in rodent models of cerebral ischemia. J Med Food 26, 436–444.CrossRefGoogle Scholar
Park, HA, Crowe-White, KM, Ciesla, L, et al. (2022) Alpha-tocotrienol enhances arborization of primary hippocampal neurons via upregulation of Bcl-xL. Nutr Res 101, 31–42.10.1016/j.nutres.2022.02.007CrossRefGoogle ScholarPubMed
Willcox, DC, Willcox, BJ, Shimajiri, S, et al. (2007) Aging gracefully: a retrospective analysis of functional status in Okinawan centenarians. Am J Geriatr Psychiatry 15, 252–256.CrossRefGoogle ScholarPubMed
Willcox, DC, Scapagnini, G & Willcox, BJ (2014) Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet. Mech Ageing Dev 136–137, 148–162.CrossRefGoogle Scholar
Peng, J, Yuan, JP, Wu, CF, et al. (2011) Fucoxanthin, a marine carotenoid present in brown seaweeds and diatoms: metabolism and bioactivities relevant to human health. Mar Drugs 9, 1806–1828.10.3390/md9101806CrossRefGoogle Scholar
Sachindra, NM, Sato, E, Maeda, H, et al. (2007) Radical scavenging and singlet oxygen quenching activity of marine carotenoid fucoxanthin and its metabolites. J Agric Food Chem 55, 8516–8522.CrossRefGoogle ScholarPubMed
Rodrigues, E, Mariutti, LR & Mercadante, AZ (2012) Scavenging capacity of marine carotenoids against reactive oxygen and nitrogen species in a membrane-mimicking system. Mar Drugs 10, 1784–1798.10.3390/md10081784CrossRefGoogle Scholar
Takashima, M, Shichiri, M, Hagihara, Y, et al. (2012) Capacity of fucoxanthin for scavenging peroxyl radicals and inhibition of lipid peroxidation in model systems. Free Radic Res 46, 1406–1412.10.3109/10715762.2012.721542CrossRefGoogle ScholarPubMed
Lee, N, Youn, K, Yoon, JH, et al. (2023) The role of fucoxanthin as a potent Nrf2 activator via Akt/GSK-3beta/Fyn axis against amyloid-beta peptide-induced oxidative damage. Antioxidants (Basel) 12, 629.10.3390/antiox12030629CrossRefGoogle ScholarPubMed
Xiang, S, Liu, F, Lin, J, et al. (2017) Fucoxanthin inhibits beta-amyloid assembly and attenuates beta-amyloid oligomer-induced cognitive impairments. J Agric Food Chem 65, 4092–4102.CrossRefGoogle ScholarPubMed
Wu, W, Han, H, Liu, J, et al. (2021) Fucoxanthin prevents 6-OHDA-induced neurotoxicity by targeting Keap1. Oxid Med Cell Longev 2021, 6688708.10.1155/2021/6688708CrossRefGoogle ScholarPubMed
Liu, J, Lu, Y, Tang, M, et al. (2022) Fucoxanthin prevents long-term administration l-DOPA-induced neurotoxicity through the ERK/JNK-c-Jun system in 6-OHDA-lesioned mice and PC12 cells. Mar Drugs 20, 245.CrossRefGoogle ScholarPubMed
Wilson, DM, Cookson, MR, Van Den Bosch, L, et al. (2023) Hallmarks of neurodegenerative diseases. Cell 186, 693–714.10.1016/j.cell.2022.12.032CrossRefGoogle ScholarPubMed
Park, HA, Licznerski, P, Alavian, KN, et al. (2015) Bcl-xL is necessary for neurite outgrowth in hippocampal neurons. Antioxid Redox Signal 22, 93–108.10.1089/ars.2013.5570CrossRefGoogle ScholarPubMed
Beaudoin, GM, Lee, SH, Singh, D, et al. (2012) Culturing pyramidal neurons from the early postnatal mouse hippocampus and cortex. Nat Protoc 7, 1741–1754.CrossRefGoogle ScholarPubMed
Kaech, S & Banker, G (2006) Culturing hippocampal neurons. Nat Protoc 1, 2406–2415.10.1038/nprot.2006.356CrossRefGoogle ScholarPubMed
Park, HA, Licznerski, P, Mnatsakanyan, N, et al. (2017) Inhibition of Bcl-xL prevents pro-death actions of DeltaN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity. Cell Death Differ 24, 1963–1974.10.1038/cdd.2017.123CrossRefGoogle ScholarPubMed
Duan, Y, Gross, RA & Sheu, SS (2007) Ca2+-dependent generation of mitochondrial reactive oxygen species serves as a signal for poly (ADP-ribose) polymerase-1 activation during glutamate excitotoxicity. J Physiol 585, 741–758.10.1113/jphysiol.2007.145409CrossRefGoogle ScholarPubMed
Park, HA, Mnatsakanyan, N, Broman, K, et al. (2019) Alpha-tocotrienol prevents oxidative stress-mediated post-translational cleavage of Bcl-xL in primary hippocampal neurons. Int J Mol Sci 21, 220.CrossRefGoogle ScholarPubMed
Alavian, KN, Beutner, G, Lazrove, E, et al. (2014) An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proc Natl Acad Sci USA 111, 10580–10585.10.1073/pnas.1401591111CrossRefGoogle Scholar
Zhang, L, Wang, H, Fan, Y, et al. (2017) Fucoxanthin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE and Nrf2-autophagy pathways. Sci Rep 7, 46763.10.1038/srep46763CrossRefGoogle ScholarPubMed
Zhang, Y, Wu, H, Wen, H, et al. (2015) Simultaneous determination of fucoxanthin and its deacetylated metabolite fucoxanthinol in rat plasma by liquid chromatography-tandem mass spectrometry. Mar Drugs 13, 6521–6536.10.3390/md13106521CrossRefGoogle ScholarPubMed
Vishwanathan, R, Neuringer, M, Snodderly, DM, et al. (2013) Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates. Nutr Neurosci 16, 21–29.10.1179/1476830512Y.0000000024CrossRefGoogle ScholarPubMed
Toomey, MB & McGraw, KJ (2007) Modified saponification and HPLC methods for analyzing carotenoids from the retina of quail: implications for its use as a nonprimate model species. Invest Ophthalmol Vis Sci 48, 3976–3982.CrossRefGoogle ScholarPubMed
Waksmundzka-Hajnos, M & Sherma, J (2011) High Performance Liquid Chromatography in Phytochemical Analysis. Chromatographic Science Series v 102, p. 1 online resource (xx, 975 pages). Boca Raton, FL: CRC Press.10.1201/b10320CrossRefGoogle Scholar
Park, HA, Stumpf, A, Broman, K, et al. (2021) Role of lycopene in mitochondrial protection during differential levels of oxidative stress in primary cortical neurons. Brain Disorders 3, 100016.10.1016/j.dscb.2021.100016CrossRefGoogle Scholar
Zhang, XS, Lu, Y, Tao, T, et al. (2020) Fucoxanthin mitigates subarachnoid hemorrhage-induced oxidative damage via sirtuin 1-dependent pathway. Mol Neurobiol 57, 5286–5298.10.1007/s12035-020-02095-xCrossRefGoogle ScholarPubMed
Jiang, X, Wang, G, Lin, Q, et al. (2019) Fucoxanthin prevents lipopolysaccharide-induced depressive-like behavior in mice via AMPK- NF-kappaB pathway. Metab Brain Dis 34, 431–442.CrossRefGoogle ScholarPubMed
Hu, L, Chen, W, Tian, F, et al. (2018) Neuroprotective role of fucoxanthin against cerebral ischemic/reperfusion injury through activation of Nrf2/HO-1 signaling. Biomed Pharmacother 106, 1484–1489.10.1016/j.biopha.2018.07.088CrossRefGoogle ScholarPubMed
Fukushima, Y, Taguchi, C, Kishimoto, Y, et al. (2023) Japanese carotenoid database with α- and beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, lycopene, and fucoxanthin and intake in adult women. Int J Vitam Nutr Res 93, 42–53.CrossRefGoogle ScholarPubMed
Nair, AB & Jacob, S (2016) A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 7, 27–31.10.4103/0976-0105.177703CrossRefGoogle ScholarPubMed
Guler, S, Gul, T, Guler, S, et al. (2021) Early-onset Parkinson’s disease: a novel deletion comprising the DJ-1 and TNFRSF9 genes. Mov Disord 36, 2973–2976.CrossRefGoogle ScholarPubMed
Hashimoto, T, Ozaki, Y, Taminato, M, et al. (2009) The distribution and accumulation of fucoxanthin and its metabolites after oral administration in mice. Br J Nutr 102, 242–248.10.1017/S0007114508199007CrossRefGoogle ScholarPubMed
Asai, A, Sugawara, T, Ono, H, et al. (2004) Biotransformation of fucoxanthinol into amarouciaxanthin A in mice and HepG2 cells: formation and cytotoxicity of fucoxanthin metabolites. Drug Metab Dispos 32, 205–211.10.1124/dmd.32.2.205CrossRefGoogle ScholarPubMed
Pruccoli, L, Balducci, M, Pagliarani, B, et al. (2024) Antioxidant and neuroprotective effects of fucoxanthin and its metabolite fucoxanthinol: a comparative in vitro study. Curr Issues Mol Biol 46, 5984–5998.10.3390/cimb46060357CrossRefGoogle ScholarPubMed
Hashimoto, T, Ozaki, Y, Mizuno, M, et al. (2012) Pharmacokinetics of fucoxanthinol in human plasma after the oral administration of kombu extract. Br J Nutr 107, 1566–1569.CrossRefGoogle Scholar
Beppu, F, Niwano, Y, Tsukui, T, et al. (2009) Single and repeated oral dose toxicity study of fucoxanthin (FX), a marine carotenoid, in mice. J Toxicol Sci 34, 501–510.CrossRefGoogle ScholarPubMed
Kumarasinghe, HS & Gunathilaka, MD (2024) A systematic review of fucoxanthin as a promising bioactive compound in drug development. Phytochem Lett 61, 52–65.10.1016/j.phytol.2024.03.009CrossRefGoogle Scholar
Lafaille-Magnan, ME, Poirier, J, Etienne, P, et al. (2017) Odor identification as a biomarker of preclinical AD in older adults at risk. Neurology 89, 327–335.10.1212/WNL.0000000000004159CrossRefGoogle ScholarPubMed
Alcolea, D, Martinez-Lage, P, Sanchez-Juan, P, et al. (2015) Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease. Neurology 85, 626–633.CrossRefGoogle ScholarPubMed
Tian, Q, Bilgel, M, Moghekar, AR, et al. (2022) Olfaction, cognitive impairment, and PET biomarkers in community-dwelling older adults. J Alzheimers Dis 86, 1275–1285.10.3233/JAD-210636CrossRefGoogle ScholarPubMed
Morgan, AR, Touchard, S, Leckey, C, et al. (2019) Inflammatory biomarkers in Alzheimer’s disease plasma. Alzheimers Dement 15, 776–787.10.1016/j.jalz.2019.03.007CrossRefGoogle ScholarPubMed
Dan, X, Wechter, N, Gray, S, et al. (2021) Olfactory dysfunction in aging and neurodegenerative diseases. Ageing Res Rev 70, 101416.CrossRefGoogle ScholarPubMed
Heinzel, S, Berg, D, Gasser, T, et al. (2019) Update of the MDS research criteria for prodromal Parkinson’s disease. Mov Disord 34, 1464–1470.CrossRefGoogle ScholarPubMed
Saramago, I & Franceschi, AM (2021) Olfactory dysfunction in neurodegenerative disease. Top Magn Reson Imaging 30, 167–172.10.1097/RMR.0000000000000271CrossRefGoogle ScholarPubMed
Paudel, P, Seong, SH, Jung, HA, et al. (2019) Characterizing fucoxanthin as a selective dopamine D(3)/D(4) receptor agonist: relevance to Parkinson’s disease. Chem Biol Interact 310, 108757.10.1016/j.cbi.2019.108757CrossRefGoogle Scholar
Kim, MS, Lee, WS, Park, Y, et al. (2022) TrkC-mediated inhibition of DJ-1 degradation is essential for direct regulation of pathogenesis of hepatocellular carcinoma. Cell Death Dis 13, 850.10.1038/s41419-022-05298-3CrossRefGoogle ScholarPubMed
Alghazwi, M, Smid, S, Musgrave, I, et al. (2019)
In vitro studies of the neuroprotective activities of astaxanthin and fucoxanthin against amyloid beta (Abeta(1–42)) toxicity and aggregation. Neurochem Int 124, 215–224.10.1016/j.neuint.2019.01.010CrossRefGoogle ScholarPubMed
Lin, J, Yu, J, Zhao, J, et al. (2017) Fucoxanthin, a marine carotenoid, attenuates beta-amyloid oligomer-induced neurotoxicity possibly via regulating the PI3K/Akt and the ERK pathways in SH-SY5Y cells. Oxid Med Cell Longev 2017, 6792543.CrossRefGoogle ScholarPubMed
Lakey-Beitia, J, Kumar, DJ, Hegde, ML, et al. (2019) Carotenoids as novel therapeutic molecules against neurodegenerative disorders: chemistry and molecular docking analysis. Int J Mol Sci 20, 5553.10.3390/ijms20225553CrossRefGoogle ScholarPubMed
Zhao, D, Kwon, SH, Chun, YS, et al. (2017) Anti-neuroinflammatory effects of fucoxanthin via inhibition of Akt/NF-kappaB and MAPKs/AP-1 pathways and activation of PKA/CREB pathway in lipopolysaccharide-activated BV-2 microglial cells. Neurochem Res 42, 667–677.10.1007/s11064-016-2123-6CrossRefGoogle ScholarPubMed
Pangestuti, R, Vo, TS, Ngo, DH, et al. (2013) Fucoxanthin ameliorates inflammation and oxidative reponses in microglia. J Agric Food Chem 61, 3876–3883.CrossRefGoogle ScholarPubMed
Brown, ES, Allsopp, PJ, Magee, PJ, et al. (2014) Seaweed and human health. Nutr Rev 72, 205–216.CrossRefGoogle ScholarPubMed