Fucoxanthin has potential for therapeutic efficacy in neurodegenerative disorders by acting on multiple targets

References

• Li X, Huang L, Lan J, Feng X, Li P, Wu L, et al. Molecular mechanisms of mitophagy and its roles in neurodegenerative diseases. Pharmacol Res. 2020;163:105240.
   PubMed Web of Science ®Google Scholar
• Lehman EJ. Epidemiology of neurodegeneration in American-style professional football players. Alzheimers Res Ther. 2013;5(4):34.
   PubMed Web of Science ®Google Scholar
• Wu H, Niu H, Shao A, Wu C, Dixon BJ, Zhang J, et al. Astaxanthin as a potential neuroprotective agent for neurological diseases. Mar Drugs. 2015;13(9):5750–5766.
   PubMed Web of Science ®Google Scholar
• Kuragano M, Yoshinari W, Lin X, Shimamori K, Uwai K, Tokuraku K. Evaluation of amyloid β(42) aggregation inhibitory activity of commercial dressings by A microliter-scale high-throughput screening system using quantum-Dot nanoprobes. Foods. 2020;9(6):825.
   Web of Science ®Google Scholar
• Rekatsina M, Paladini A, Piroli A, Zis P, Pergolizzi JV, Varrassi G. Pathophysiology and therapeutic perspectives of oxidative stress and neurodegenerative diseases: a narrative review. Adv Ther. 2020;37(1):113–139.
   PubMed Web of Science ®Google Scholar
• Subhramanyam CS, Wang C, Hu Q, Dheen ST. Microglia-mediated neuroinflammation in neurodegenerative diseases. Semin Cell Dev Biol. 2019;94:112–120.
   PubMed Web of Science ®Google Scholar
• Daverey A, Agrawal SK. Curcumin alleviates oxidative stress and mitochondrial dysfunction in astrocytes. Neuroscience. 2016;333:92–103.
   PubMed Web of Science ®Google Scholar
• Toublet FX, Lecoutey C, Lalut J, Hatat B, Davis A, Since M, et al. Inhibiting acetylcholinesterase to activate pleiotropic prodrugs with therapeutic interest in Alzheimer’s disease. Molecules. 2019;24(15):2786.
   Web of Science ®Google Scholar
• Bostanciklioğlu M. The role of gut microbiota in pathogenesis of Alzheimer’s disease. J Appl Microbiol. 2019;127(4):954–967.
   PubMed Web of Science ®Google Scholar
• Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease–a double-edged sword. Neuron. 2002;35(3):419–432.
   PubMed Web of Science ®Google Scholar
• Gontijo VS, Viegas FPD, Ortiz CJC, de Freitas Silva M, Damasio CM, Rosa MC, et al. Molecular hybridization as a tool in the design of multi-target directed drug candidates for neurodegenerative diseases. Curr Neuropharmacol. 2020;18(5):348–407.
   PubMed Web of Science ®Google Scholar
• Zhang P, Xu S, Zhu Z, Xu J. Multi-target design strategies for the improved treatment of Alzheimer’s disease. Eur J Med Chem. 2019;176:228–247.
   PubMed Web of Science ®Google Scholar
• Ruan Q, Ruan J, Zhang W, Qian F, Yu Z. Targeting NAD(+) degradation: the therapeutic potential of flavonoids for Alzheimer’s disease and cognitive frailty. Pharmacol Res. 2018;128:345–358.
   PubMed Web of Science ®Google Scholar
• Botchway BOA, Moore MK, Akinleye FO, Iyer IC, Fang M. Nutrition: review on the possible treatment for Alzheimer’s disease. J Alzheimers Dis. 2018;61(3):867–883.
   PubMed Web of Science ®Google Scholar
• Syed YY. Sodium oligomannate: first approval. Drugs. 2020;80(4):441–444.
   PubMed Web of Science ®Google Scholar
• Galasso C, Orefice I, Pellone P, Cirino P, Miele R, Ianora A, et al. On the neuroprotective role of astaxanthin: new perspectives? Mar Drugs. 2018;16(8):247.
   PubMed Web of Science ®Google Scholar
• Miyashita K. Function of marine carotenoids. Forum Nutr. 2009;61:136–146.
   PubMedGoogle Scholar
• Dembitsky VM, Maoka T. Allenic and cumulenic lipids. Prog Lipid Res. 2007;46(6):328–375.
   PubMed Web of Science ®Google Scholar
• Zhu J, Sun X, Chen X, Wang S, Wang D. Chemical cleavage of fucoxanthin from Undaria pinnatifida and formation of apo-fucoxanthinones and apo-fucoxanthinals identified using LC-DAD-APCI-MS/MS. Food Chem. 2016;211:365–373.
   PubMed Web of Science ®Google Scholar
• Lourenço-Lopes C, Garcia-Oliveira P, Carpena M, Fraga-Corral M, Jimenez-Lopez C, Pereira AG, et al. Scientific approaches on extraction, purification and stability for the commercialization of fucoxanthin recovered from brown algae. Foods. 2020;9(8):1113.
   PubMed Web of Science ®Google Scholar
• Fiedor J, Burda K. Potential role of carotenoids as antioxidants in human health and disease. Nutrients. 2014;6(2):466–488.
   PubMed Web of Science ®Google Scholar
• Haoujar I, Cacciola F, Abrini J, Mangraviti D, Giuffrida D, Oulad El Majdoub Y, et al. The contribution of carotenoids, phenolic compounds, and flavonoids to the antioxidative properties of marine microalgae isolated from Mediterranean Morocco. Molecules. 2019;24(22):4037.
   Web of Science ®Google Scholar
• Rodrigues E, Mariutti LR, Mercadante AZ. Scavenging capacity of marine carotenoids against reactive oxygen and nitrogen species in a membrane-mimicking system. Mar Drugs. 2012;10(8):1784–1798.
   PubMed Web of Science ®Google Scholar
• Fung A, Hamid N, Lu J. Fucoxanthin content and antioxidant properties of Undaria pinnatifida. Food Chem. 2013;136(2):1055–1062.
   PubMed Web of Science ®Google Scholar
• Peng J, Yuan JP, Wu CF, Wang JH. Fucoxanthin, a marine carotenoid present in brown seaweeds and diatoms: metabolism and bioactivities relevant to human health. Mar Drugs. 2011;9(10):1806–1828.
   PubMed Web of Science ®Google Scholar
• Woo MN, Jeon SM, Shin YC, Lee MK, Kang MAChoi MS. Anti-obese property of fucoxanthin is partly mediated by altering lipid-regulating enzymes and uncoupling proteins of visceral adipose tissue in mice. Mol Nutr Food Res. 2009;53(12):1603–1611.
   PubMed Web of Science ®Google Scholar
• Chukwuma CI, Matsabisa MG, Ibrahim MA, Erukainure OL, Chabalala MH, Islam MS. Medicinal plants with concomitant anti-diabetic and anti-hypertensive effects as potential sources of dual acting therapies against diabetes and hypertension: a review. J Ethnopharmacol. 2019;235:329–360.
   PubMed Web of Science ®Google Scholar
• Pugazhenthi S, Qin L, Reddy PH. Common neurodegenerative pathways in obesity, diabetes, and Alzheimer’s disease. Biochim Biophys Acta Mol Basis Dis. 2017;1863(5):1037–1045.
   PubMed Web of Science ®Google Scholar
• Sun Q, Liu F, Sang J, Lin M, Ma J, Xiao X, et al. 9-Methylfascaplysin is a more potent Aβ aggregation inhibitor than the marine-derived alkaloid, fascaplysin, and produces nanomolar neuroprotective effects in SH-SY5Y cells. Mar Drugs. 2019;17(2):121.
   Web of Science ®Google Scholar
• Xiang S, Liu F, Lin J, Chen H, Huang C, Chen L, et al. Fucoxanthin inhibits β-amyloid assembly and attenuates β-amyloid oligomer-induced cognitive impairments. J Agric Food Chem. 2017;65(20):4092–4102.
   PubMed Web of Science ®Google Scholar
• Kim S-K, Pangestuti R. Biological activities and potential health benefits of fucoxanthin derived from marine brown algae. Adv Food Nutr Res. 2011;64:111–128.
   PubMedGoogle Scholar
• Filippov MA, Tatarnikova OG, Pozdnyakova NV, Vorobyov VV. Inflammation/bioenergetics-associated neurodegenerative pathologies and concomitant diseases: a role of mitochondria targeted catalase and xanthophylls. Neural Regen Res. 2021;16(2):223–233.
   PubMed Web of Science ®Google Scholar
• Stahl W, Sies H. Antioxidant activity of carotenoids. Mol Aspects Med. 2003;24(6):345–351.
   PubMed Web of Science ®Google Scholar
• Ramel F, Birtic S, Cuiné S, Triantaphylidès C, Ravanat JL, Havaux M. Chemical quenching of singlet oxygen by carotenoids in plants. Plant Physiol. 2012;158(3):1267–1278.
   PubMed Web of Science ®Google Scholar
• Muradian K, Vaiserman A, Min KJ, Fraifeld VE. Fucoxanthin and lipid metabolism: a minireview. Nutr Metab Cardiovasc Dis. 2015;25(10):891–897.
   PubMed Web of Science ®Google Scholar
• Sachindra NM, Sato E, Maeda H, Hosokawa M, Niwano Y, Kohno M, et al. Radical scavenging and singlet oxygen quenching activity of marine carotenoid fucoxanthin and its metabolites. J Agric Food Chem. 2007;55(21):8516–8522.
   PubMed Web of Science ®Google Scholar
• Zhao D, Kim SM, Pan CH, Chung D. Effects of heating, aerial exposure and illumination on stability of fucoxanthin in canola oil. Food Chem. 2014;145:505–513.
   PubMed Web of Science ®Google Scholar
• Aman R, Schieber A, Carle R. Effects of heating and illumination on trans-cis isomerization and degradation of beta-carotene and lutein in isolated spinach chloroplasts. J Agric Food Chem. 2005;53(24):9512–9518.
   PubMed Web of Science ®Google Scholar
• Zhao D, Yu D, Kim M, Gu MY, Kim SM, Pan CH, et al. Effects of temperature, light, and pH on the stability of fucoxanthin in an oil-in-water emulsion. Food Chem. 2019;291:87–93.
   PubMed Web of Science ®Google Scholar
• Aungst BJ. Optimizing oral bioavailability in drug discovery: an overview of design and testing strategies and Formulation options. J Pharm Sci. 2017;106(4):921–929.
   PubMed Web of Science ®Google Scholar
• Rawson NSBD’Arcy C. Healthcare databases for drug safety research: data validity assessment remains crucial. Drug Saf. 2018;41(9):829–833.
   PubMed Web of Science ®Google Scholar
• Zhao C, Yang C, Liu B, Lin L, Sarker SD, Nahar L, et al. Bioactive compounds from marine macroalgae and their hypoglycemic benefits. Trends Food Sci Technol. 2018;72:1–12.
   Web of Science ®Google Scholar
• Suri BK, Schmidtchen A, Verma NK. Carbonic anhydrases in human keratinocytes and their regulation by all-trans retinoic acid and 1α,25-dihydroxyvitamin D(3). Exp Dermatol. 2019;28(8):976–980.
   PubMed Web of Science ®Google Scholar
• Asai A, Sugawara T, Ono HNagao A. Biotransformation of fucoxanthinol into amarouciaxanthin A in mice and HepG2 cells: formation and cytotoxicity of fucoxanthin metabolites. Drug Metab Dispos. 2004;32(2):205–211.
   PubMed Web of Science ®Google Scholar
• Hashimoto T, Ozaki Y, Taminato M, Das SK, Mizuno M, Yoshimura K, et al. The distribution and accumulation of fucoxanthin and its metabolites after oral administration in mice. Br J Nutr. 2009;102(2):242–248.
   PubMed Web of Science ®Google Scholar
• Maoka T. Carotenoids in marine animals. Mar Drugs. 2011;9(2):278–293.
   PubMed Web of Science ®Google Scholar
• Li Y, Liu L, Sun P, Zhang Y, Wu T, Sun H, et al. Fucoxanthinol from the Diatom Nitzschia Laevis ameliorates neuroinflammatory responses in lipopolysaccharide-stimulated BV-2 microglia. Mar Drugs. 2020;18(2):116.
   Web of Science ®Google Scholar
• Jin W, Yang L, Yi Z, Fang H, Chen W, Hong Z, et al. Anti-inflammatory effects of fucoxanthinol in LPS-induced RAW264.7 cells through the NAAA-PEA pathway. Mar Drugs. 2020;18(4):222.
   Web of Science ®Google Scholar
• Bae M, Kim MB, Park YK, Lee JY. Health benefits of fucoxanthin in the prevention of chronic diseases. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865(11):158618.
   PubMed Web of Science ®Google Scholar
• Zhang L, Wang H, Fan Y, Gao Y, Li X, Hu Z, et al. Fucoxanthin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE and Nrf2-autophagy pathways. Sci Rep. 2017;7:46763.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Wu H, Wen H, Fang H, Hong Z, Yi R, et al. Simultaneous determination of fucoxanthin and Its deacetylated metabolite fucoxanthinol in Rat plasma by liquid chromatography-tandem mass spectrometry. Mar Drugs. 2015;13(10):6521–6536.
   PubMed Web of Science ®Google Scholar
• Liu Y, Qiao Z, Liu W, Hou Z, Zhang D, Huang L, et al. Oleic acid as a protein ligand improving intestinal absorption and ocular benefit of fucoxanthin in water through protein-based encapsulation. Food Funct. 2019;10(7):4381–4395.
   PubMed Web of Science ®Google Scholar
• Mok IK, Lee JK, Kim JH, Pan CH, Kim SM. Fucoxanthin bioavailability from fucoxanthin-fortified milk: in vivo and in vitro study. Food Chem. 2018;258:79–86.
   PubMed Web of Science ®Google Scholar
• Noviendri D, Jaswir I, Taher M, Mohamed F, Salleh HM, Noorbatcha IA, et al. Fabrication of Fucoxanthin-Loaded microsphere(F-LM) by two steps double-emulsion solvent evaporation method and characterization of fucoxanthin before and after microencapsulation. J Oleo Sci. 2016;65(8):641–653.
   PubMed Web of Science ®Google Scholar
• Jaswir I, Noviendri D, Taher M, Mohamed F, Octavianti F, Lestari W, et al. Optimization and formulation of fucoxanthin-loaded microsphere (F-LM) using response surface methodology (RSM) and analysis of its fucoxanthin release profile. Molecules. 2019;24(5):947.
   PubMed Web of Science ®Google Scholar
• Zhao J, Liu F, Huang C, Shentu J, Wang M, Sun C, et al. 5-Hydroxycyclopenicillone inhibits β-amyloid oligomerization and produces anti-β-amyloid neuroprotective effects in vitro. Molecules. 2017;22(10):1651.
   Web of Science ®Google Scholar
• Beppu F, Niwano Y, Sato E, Kohno M, Tsukui T, Hosokawa M, et al. In vitro and in vivo evaluation of mutagenicity of fucoxanthin (FX) and its metabolite fucoxanthinol (FXOH). J Toxicol Sci. 2009;34(6):693–698.
   PubMed Web of Science ®Google Scholar
• Beppu F, Niwano Y, Tsukui T, Hosokawa M, Miyashita K. Single and repeated oral dose toxicity study of fucoxanthin (FX), a marine carotenoid, in mice. J Toxicol Sci. 2009;34(5):501–510.
   PubMed Web of Science ®Google Scholar
• Iio K, Okada Y, Ishikura M. Single and 13-week oral toxicity study of fucoxanthin oil from microalgae in rats. Shokuhin Eiseigaku Zasshi. 2011;52(3):183–189.
   PubMed Web of Science ®Google Scholar
• Yim SK, Kim K, Chun S, Oh T, Jung W, Jung K, et al. Screening of human CYP1A2 and CYP3A4 inhibitors from seaweed In silico and In vitro. Mar Drugs. 2020;18(12):603.
   PubMed Web of Science ®Google Scholar
• Hitoe S, Shimoda H. Seaweed fucoxanthin supplementation improves obesity parameters in mild Obese Japanese Subjects. 2017.
   Google Scholar
• Abidov M, Ramazanov Z, Seifulla R, Grachev S. The effects of xanthigen in the weight management of obese premenopausal women with non-alcoholic fatty liver disease and normal liver fat. Diabetes Obes Metab. 2010;12(1):72–81.
   PubMed Web of Science ®Google Scholar
• Wang X, Sun G, Feng T, Zhang J, Huang X, Wang T, et al. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression. Cell Res. 2019;29(10):787–803.
   PubMed Web of Science ®Google Scholar
• Lim JYue Z. Neuronal aggregates: formation, clearance, and spreading. Dev Cell. 2015;32(4):491–501.
   PubMed Web of Science ®Google Scholar
• Chu YF, Chang WH, Black RM, Liu JR, Sompol P, Chen Y, et al. Crude caffeine reduces memory impairment and amyloid β(1-42) levels in an Alzheimer’s mouse model. Food Chem. 2012;135(3):2095–2102.
   PubMed Web of Science ®Google Scholar
• Afzal S, Garg S, Ishida Y, Terao K, Kaul SC, Wadhwa R. Rat glioma cell-based functional characterization of anti-stress and protein deaggregation activities in the marine carotenoids, astaxanthin and fucoxanthin. Mar Drugs. 2019;17(3):189.
   PubMed Web of Science ®Google Scholar
• Ayyalasomayajula N, Suresh C. Mechanistic comparison of current pharmacological treatments and novel phytochemicals to target amyloid peptides in Alzheimer’s and neurodegenerative diseases. Nutr Neurosci. 2018;21(10):682–694.
   PubMed Web of Science ®Google Scholar
• Ferreira ST, Klein WL. The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease. Neurobiol Learn Mem. 2011;96(4):529–543.
   PubMed Web of Science ®Google Scholar
• Lee S, Choi BR, Kim J, LaFerla FM, Park JHY, Han JS, et al. Sulforaphane upregulates the heat shock protein Co-chaperone CHIP and clears amyloid-β and Tau in a mouse model of Alzheimer’s disease. Mol Nutr Food Res. 2018;62(12):240.
   Web of Science ®Google Scholar
• Doggui S, Belkacemi A, Paka GD, Perrotte M, Pi R, Ramassamy C. Curcumin protects neuronal-like cells against acrolein by restoring Akt and redox signaling pathways. Mol Nutr Food Res. 2013;57(9):1660–1670.
   PubMed Web of Science ®Google Scholar
• Gu MY, Chun YS, Zhao D, Ryu SY, Yang HO. Glycyrrhiza uralensis and semilicoisoflavone B reduce Aβ secretion by increasing PPARγ expression and inhibiting STAT3 phosphorylation to inhibit BACE1 expression. Mol Nutr Food Res. 2018;62(6):633.
   Web of Science ®Google Scholar
• Jung HA, Ali MY, Choi RJ, Jeong HO, Chung HY, Choi JS. Kinetics and molecular docking studies of fucosterol and fucoxanthin, BACE1 inhibitors from brown algae Undaria pinnatifida and Ecklonia stolonifera. Food Chem Toxicol. 2016;89:104–111.
   PubMed Web of Science ®Google Scholar
• Zhao X, Pu XP Neuroprotective effect of fucoxanthin on β-amyloid-induced cell death. Chin Pharm. 2015;24(7):60.
   Google Scholar
• Alghazwi M, Smid S, Musgrave I, Zhang W. In vitro studies of the neuroprotective activities of astaxanthin and fucoxanthin against amyloid beta (Aβ(1-42)) toxicity and aggregation. Neurochem Int. 2019;124:215–224.
   PubMed Web of Science ®Google Scholar
• Singh A, Kukreti R, Saso LKukreti S. Oxidative stress: A key modulator in neurodegenerative diseases. Molecules. 2019;24(8):1583.
   PubMed Web of Science ®Google Scholar
• Rao AV, Balachandran B. Role of oxidative stress and antioxidants in neurodegenerative diseases. Nutr Neurosci. 2002;5(5):291–309.
   PubMed Web of Science ®Google Scholar
• Meng X, Zhou J, Zhao CN, Gan RY, Li HB. Health benefits and molecular mechanisms of resveratrol: a narrative review. Foods. 2020;9(3):340.
   PubMed Web of Science ®Google Scholar
• Harvey CJ, Thimmulappa RK, Singh A, Blake DJ, Ling G, Wakabayashi N, et al. Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress. Free Radic Biol Med. 2009;46(4):443–453.
   PubMed Web of Science ®Google Scholar
• Zheng J, Piao MJ, Kim KC, Yao CW, Cha JW, Hyun JW. Fucoxanthin enhances the level of reduced glutathione via the Nrf2-mediated pathway in human keratinocytes. Mar Drugs. 2014;12(7):4214–4230.
   PubMed Web of Science ®Google Scholar
• Wang X, Cui YJ, Qi J, Zhu MM, Zhang TL, Cheng M, et al. Fucoxanthin exerts cytoprotective effects against hydrogen peroxide-induced oxidative damage in L02 cells. Biomed Res Int. 2018;1085073:1–11.
   Google Scholar
• Zhao D, Kwon SH, Chun YS, Gu MY, Yang HO. Anti-Neuroinflammatory effects of fucoxanthin via inhibition of Akt/NF-κB and MAPKs/AP-1 pathways and activation of PKA/CREB pathway in lipopolysaccharide-activated BV-2 microglial cells. Neurochem Res. 2017;42(2):667–677.
   PubMed Web of Science ®Google Scholar
• Hu L, Chen W, Tian F, Yuan C, Wang H, Yue H. Neuroprotective role of fucoxanthin against cerebral ischemic/reperfusion injury through activation of Nrf2/HO-1 signaling. Biomed Pharmacother. 2018;106:1484–1489.
   PubMed Web of Science ®Google Scholar
• Pangestuti R, Vo TS, Ngo DH, Kim SK. Fucoxanthin ameliorates inflammation and oxidative reponses in microglia. J Agric Food Chem. 2013;61(16):3876–3883.
   PubMed Web of Science ®Google Scholar
• Yu J, Lin JJ, Yu R, He S, Wang QW, Cui W, et al. Fucoxanthin prevents H(2)O(2)-induced neuronal apoptosis via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway. Food Nutr Res. 2017;61(1):1304678–1304678.
   PubMed Web of Science ®Google Scholar
• García F, Lobos P, Ponce A, Cataldo K, Meza D, Farías P, et al. Astaxanthin counteracts excitotoxicity and reduces the ensuing increases in calcium levels and mitochondrial reactive oxygen species generation. Mar Drugs. 2020;18(6):335.
   Web of Science ®Google Scholar
• Chan KC, Mong MC, Yin MC. Antioxidative and anti-inflammatory neuroprotective effects of astaxanthin and canthaxanthin in nerve growth factor differentiated PC12 cells. J Food Sci. 2009;74(7):H225–231.
   PubMed Web of Science ®Google Scholar
• Roeckel LA, Le Coz GM, Gavériaux-Ruff CSimonin F. Opioid-induced hyperalgesia: cellular and molecular mechanisms. Neuroscience. 2016;338:160–182.
   PubMed Web of Science ®Google Scholar
• Ishihara Y, Takemoto T, Itoh K, Ishida A, Yamazaki T. Dual role of superoxide dismutase 2 induced in activated microglia: oxidative stress tolerance and convergence of inflammatory responses. J Biol Chem. 2015;290(37):22805–22817.
   PubMed Web of Science ®Google Scholar
• Seo EJ, Fischer N, Efferth T. Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer’s disease. Pharmacol Res. 2018;129:262–273.
   PubMed Web of Science ®Google Scholar
• Xu L, He D, Bai Y. Microglia-Mediated inflammation and neurodegenerative disease. Mol Neurobiol. 2016;53(10):6709–6715.
   PubMed Web of Science ®Google Scholar
• Ho SC, Chang KS, Chang PW. Inhibition of neuroinflammation by cinnamon and its main components. Food Chem. 2013;138(4):2275–2282.
   PubMed Web of Science ®Google Scholar
• Rose KN, Barlock BJ, DaSilva NA, Johnson SL, Liu C, Ma H, et al. Anti-neuroinflammatory effects of a food-grade phenolic-enriched maple syrup extract in a mouse model of Alzheimer’s disease. Nutr Neurosci. 2019;10:1–10.
   Google Scholar
• Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci. 2007;8(1):57–69.
   PubMed Web of Science ®Google Scholar
• Stringham JM, Stringham NT. Nitric oxide and lutein: function, performance, and protection of neural tissue. Foods. 2015;4(4):678–689.
   PubMed Web of Science ®Google Scholar
• Kim KN, Heo SJ, Yoon WJ, Kang SM, Ahn G, Yi TH, et al. Fucoxanthin inhibits the inflammatory response by suppressing the activation of NF-κB and MAPKs in lipopolysaccharide-induced RAW 264.7 macrophages. Eur J Pharmacol. 2010;649(1-3):369–375.
   PubMed Web of Science ®Google Scholar
• Park HY, Han MH, Park C, Jin CY, Kim GY, Choi IW, et al. Anti-inflammatory effects of fucoidan through inhibition of NF-κB, MAPK and Akt activation in lipopolysaccharide-induced BV2 microglia cells. Food Chem Toxicol. 2011;49(8):1745–1752.
   PubMed Web of Science ®Google Scholar
• Wang J, Li L, Wang Z, Cui Y, Tan X, Yuan T, et al. Supplementation of lycopene attenuates lipopolysaccharide-induced amyloidogenesis and cognitive impairments via mediating neuroinflammation and oxidative stress. J Nutr Biochem. 2018;56:16–25.
   PubMed Web of Science ®Google Scholar
• Jasmina DS, Ljupcho K, Lee V. Potential beneficial actions of fucoidan in brain and liver injury, disease, and intoxication-potential implication of sirtuins. Mar Drugs. 2020;18(5):242.
   Web of Science ®Google Scholar
• Jiang X, Wang G, Lin Q, Tang Z, Yan Q, Yu X. Fucoxanthin prevents lipopolysaccharide-induced depressive-like behavior in mice via AMPK- NF-κB pathway. Metab Brain Dis. 2019;34(2):431–442.
   PubMed Web of Science ®Google Scholar
• Sun G, Xin T, Zhang R, Liu C, Pang Q. Fucoxanthin attenuates behavior deficits and neuroinflammatory response in 1-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine-induced Parkinson’s disease in mice. Pharmacogn Mag. 2020;16(67):51.
   Web of Science ®Google Scholar
• Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, et al. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol. 2014;112:24–49.
   PubMed Web of Science ®Google Scholar
• Youssef SB, Brisson G, Doucet-Beaupré H, Castonguay AM, Gora C, Amri M, et al. Neuroprotective benefits of grape seed and skin extract in a mouse model of Parkinson’s disease. Nutr Neurosci. 2019;24(3):197–211.
   PubMed Web of Science ®Google Scholar
• Xu J, Wang H, Lu X, Ding K, Zhang L, He J, et al. Posttraumatic administration of luteolin protects mice from traumatic brain injury: implication of autophagy and inflammation. Brain Res. 2014;1582:237–246.
   PubMed Web of Science ®Google Scholar
• Li J, Wang F, Xia Y, Dai W, Chen K, Li S, et al. Astaxanthin pretreatment attenuates hepatic ischemia reperfusion-induced apoptosis and autophagy via the ROS/MAPK pathway in mice. Mar Drugs. 2015;13(6):3368–3387.
   PubMed Web of Science ®Google Scholar
• Qu M, Li L, Chen C, Li M, Pei L, Chu F, et al. Protective effects of lycopene against amyloid β-induced neurotoxicity in cultured rat cortical neurons. Neurosci Lett. 2011;505(3):286–290.
   PubMed Web of Science ®Google Scholar
• Nataraj J, Manivasagam T, Thenmozhi AJ, Essa MM. Lutein protects dopaminergic neurons against MPTP-induced apoptotic death and motor dysfunction by ameliorating mitochondrial disruption and oxidative stress. Nutr Neurosci. 2016;19(6):237–246.
   PubMed Web of Science ®Google Scholar
• Gibb AJ. (2001). Neurotransmitter Receptors.
   Google Scholar
• Wang Y, Guan X, Chen X, Cai Y, Ma Y, Ma J, et al. Choline supplementation ameliorates behavioral deficits and Alzheimer’s disease-like pathology in transgenic APP/PS1 mice. Mol Nutr Food Res. 2019;63(18):1407.
   Web of Science ®Google Scholar
• Weon JB, Lee J, Eom MR, Jung YS, Ma CJ. Cognitive enhancing effect of the fermented gumiganghwal-tang on scopolamine-induced memory impairment in mice. Nutr Neurosci. 2016;19(3):125–130.
   PubMed Web of Science ®Google Scholar
• Bullock RLane R. Executive dyscontrol in dementia, with emphasis on subcortical pathology and the role of butyrylcholinesterase. Curr Alzheimer Res. 2007;4(3):277–293.
   PubMed Web of Science ®Google Scholar
• Hung SY, Fu WM. Drug candidates in clinical trials for Alzheimer’s disease. J Biomed Sci. 2017;24(1):47–47.
   PubMed Web of Science ®Google Scholar
• Kandiah N, Pai MC, Senanarong V, Looi I, Ampil E, Park KW, et al. Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson’s disease dementia. Clin Interv Aging. 2017;12:697–707.
   PubMed Web of Science ®Google Scholar
• Lin J, Huang L, Yu J, Xiang S, Wang J, Zhang J, et al. Fucoxanthin, a marine carotenoid, reverses scopolamine-induced cognitive impairments in mice and inhibits Acetylcholinesterase in vitro. Mar Drugs. 2016;14(4):67.
   Web of Science ®Google Scholar
• Grella Miranda C, Dos Santos PDF, do Prado Silva JT, Vitória Leimann F, Ferreira Borges B, Miguel Abreu R, et al. Influence of nanoencapsulated lutein on acetylcholinesterase activity: In vitro determination, kinetic parameters, and in silico docking simulations. Food Chem. 2020;307:125523.
   PubMed Web of Science ®Google Scholar
• Kawee-ai A, Kuntiya A, Kim SM. Anticholinesterase and antioxidant activities of fucoxanthin purified from the microalga phaeodactylum tricornutum. Nat Prod Commun. 2013;8(10):1381–1386.
   PubMed Web of Science ®Google Scholar
• Sutachan JJ, Casas Z, Albarracin SL, Stab BR, 2nd., Samudio I, Gonzalez J, et al. Cellular and molecular mechanisms of antioxidants in Parkinson’s disease. Nutr Neurosci. 2012;15(3):120–126.
   PubMed Web of Science ®Google Scholar
• Kang SS, Ahn EH, Zhang Z, Liu X, Manfredsson FP, Sandoval IM, et al. α-Synuclein stimulation of monoamine oxidase-B and legumain protease mediates the pathology of Parkinson’s disease. Embo j. 2018;37(12):e98878.
   PubMed Web of Science ®Google Scholar
• Gray R, Ives N, Rick C, Patel S, Gray A, Jenkinson C, et al. Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson’s disease (PD MED): a large, open-label, pragmatic randomised trial. Lancet. 2014;384(9949):1196–1205.
   PubMed Web of Science ®Google Scholar
• Paudel P, Seong SH, Jung HA, Choi JS. Characterizing fucoxanthin as a selective dopamine D(3)/D(4) receptor agonist: relevance to Parkinson’s disease. Chem Biol Interact. 2019;310:108757.
   PubMed Web of Science ®Google Scholar
• Zhang L, Hao J, Zheng Y, Su R, Liao Y, Gong X, et al. Fucoidan protects dopaminergic neurons by enhancing the mitochondrial function in a rotenone-induced Rat model of Parkinson’s disease. Aging Dis. 2018;9(4):590–604.
   PubMed Web of Science ®Google Scholar
• Jung HA, Roy A, Choi JS. In vitro monoamine oxidase A and B inhibitory activity and molecular docking simulations of fucoxanthin. Fish Sci. 2017;83(1):123–132.
   Web of Science ®Google Scholar
• Ni Y, Yang X, Zheng L, Wang Z, Wu L, Jiang J, et al. Lactobacillus and bifidobacterium improves physiological function and cognitive ability in aged mice by the regulation of Gut microbiota. Mol Nutr Food Res. 2019;63(22):e1900603.
   PubMed Web of Science ®Google Scholar
• Bianchi VE, Herrera PF, Laura R. Effect of nutrition on neurodegenerative diseases. A systematic review. Nutr Neurosci. 2019: 1–25.
   PubMed Web of Science ®Google Scholar
• Hoffman JD, Parikh I, Green SJ, Chlipala G, Mohney RP, Keaton M, et al. Age drives distortion of brain metabolic, vascular and cognitive functions, and the Gut microbiome. Front Aging Neurosci. 2017;9:298.
   PubMed Web of Science ®Google Scholar
• Bedarf JR, Hildebrand F, Goeser F, Bork P, Wüllner U. The gut microbiome in Parkinson’s disease. Nervenarzt. 2019;90(2):160–166.
   PubMed Web of Science ®Google Scholar
• Guo B, Yang B, Pang X, Chen T, Chen F, Cheng KW. Fucoxanthin modulates cecal and fecal microbiota differently based on diet. Food Funct. 2019;10(9):5644–5655.
   PubMed Web of Science ®Google Scholar