Antioxidant and Neuroprotective Effects of Fucoxanthin and Its Metabolite Fucoxanthinol: A Comparative In Vitro Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Cell Culture and Preparation of Carotenoid Solutions
2.3. Determination of Neuronal Viability
2.4. Determination of Total Antioxidant Activity (TAA)
2.5. Determination of TAA in Membrane and Cytoplasm of SH-SY5Y Cells
2.6. Determination of Antioxidant Activity in SH-SY5Y Cells
2.7. Determination of Glutathione Levels
2.8. Determination of Keap1 and Nrf2 Protein Levels
2.9. Determination of Nrf2 and Nrf2-Target Gene Expression
2.10. Determination of Neuroprotective Activity against Aβ1–42 Oligomers
2.11. Determination of Neuroprotective Activity against 6-OHDA
2.12. Statistical Analysis
3. Results and Discussion
3.1. Antioxidant Activity of Carotenoids
3.2. Effects of Carotenoids on Neuronal Antioxidant Response
3.3. Neuroprotective Effects of Carotenoids against the Neurotoxicity Induced by AβO and 6-OHDA
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Peng, J.; Yuan, J.-P.; Wu, C.-F.; Wang, J.-H. Fucoxanthin, a Marine Carotenoid Present in Brown Seaweeds and Diatoms: Metabolism and Bioactivities Relevant to Human Health. Mar. Drugs 2011, 9, 1806–1828. [Google Scholar] [CrossRef] [PubMed]
- 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, 431–442. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef]
- Zhang, L.; Wang, H.; Fan, Y.; Gao, Y.; Li, X.; Hu, Z.; Ding, K.; Wang, Y.; Wang, X. Fucoxanthin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE and Nrf2-autophagy pathways. Sci. Rep. 2017, 7, 46763. [Google Scholar] [CrossRef]
- Xiang, S.; Liu, F.; Lin, J.; Chen, H.; Huang, C.; Chen, L.; Zhou, Y.; Ye, L.; Zhang, K.; Jin, J.; et al. Fucoxanthin Inhibits β-Amyloid Assembly and Attenuates β-Amyloid Oligomer-Induced Cognitive Impairments. J. Agric. Food Chem. 2017, 65, 4092–4102. [Google Scholar] [CrossRef]
- Jung, H.A.; Ali, M.Y.; Choi, R.J.; Jeong, H.O.; Chung, H.Y.; Choi, J.S. 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. [Google Scholar] [CrossRef] [PubMed]
- Lin, J.; Yu, J.; Zhao, J.; Zhang, K.; Zheng, J.; Wang, J.; Huang, C.; Zhang, J.; Yan, X.; Gerwick, W.H.; et al. Fucoxanthin, a Marine Carotenoid, Attenuates β-Amyloid Oligomer-Induced Neurotoxicity Possibly via Regulating the PI3K/Akt and the ERK Pathways in SH-SY5Y Cells. Oxid. Med. Cell. Longev. 2017, 2017, 1–10. [Google Scholar] [CrossRef]
- Pangestuti, R.; Vo, T.-S.; Ngo, D.-H.; Kim, S.-K. Fucoxanthin Ameliorates Inflammation and Oxidative Reponses in Microglia. J. Agric. Food Chem. 2013, 61, 3876–3883. [Google Scholar] [CrossRef] [PubMed]
- Yu, J.; Lin, J.-J.; Yu, R.; He, S.; Wang, Q.-W.; Cui, W.; Zhang, J.-R. Fucoxanthin prevents H2O2-induced neuronal apoptosis via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway. Food Nutr. Res. 2017, 61, 1304678. [Google Scholar] [CrossRef]
- Lin, J.; Huang, L.; Yu, J.; Xiang, S.; Wang, J.; Zhang, J.; Yan, X.; Cui, W.; He, S.; Wang, Q. Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro. Mar. Drugs 2016, 14, 67. [Google Scholar] [CrossRef]
- 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, 51. [Google Scholar] [CrossRef]
- Paudel, P.; Seong, S.H.; Jung, H.A.; Choi, J.S. Characterizing fucoxanthin as a selective dopamine D3/D4 receptor agonist: Relevance to Parkinson’s disease. Chem. Biol. Interact. 2019, 310, 108757. [Google Scholar] [CrossRef] [PubMed]
- Jung, H.A.; Roy, A.; Choi, J.S. In vitro monoamine oxidase A and B inhibitory activity and molecular docking simulations of fucoxanthin. Fish. Sci. 2017, 83, 123–132. [Google Scholar] [CrossRef]
- Asai, A.; Sugawara, T.; Ono, H.; Nagao, A. Biotransformation of fucoxanthinol into amarouciaxanthin A in mice and HepG2 cells: Formation and cytotoxicity of fucoxanthin metabolites. Drug Metab. Dispos. 2004, 32, 205–211. [Google Scholar] [CrossRef] [PubMed]
- Hashimoto, T.; Ozaki, Y.; Taminato, M.; Das, S.K.; Mizuno, M.; Yoshimura, K.; Maoka, T.; Kanazawa, K. The distribution and accumulation of fucoxanthin and its metabolites after oral administration in mice. Br. J. Nutr. 2009, 102, 242–248. [Google Scholar] [CrossRef] [PubMed]
- Takatani, N.; Sakimura, K.; Nagata, K.; Beppu, F.; Yamano, Y.; Maoka, T.; Hosokawa, M. Identification and tissue distribution of fucoxanthinol and amarouciaxanthin A fatty acid esters in fucoxanthin-fed mice. Food Chem. 2023, 410, 135318. [Google Scholar] [CrossRef] [PubMed]
- Hashimoto, T.; Ozaki, Y.; Mizuno, M.; Yoshida, M.; Nishitani, Y.; Azuma, T.; Komoto, A.; Maoka, T.; Tanino, Y.; Kanazawa, K. Pharmacokinetics of fucoxanthinol in human plasma after the oral administration of kombu extract. Br. J. Nutr. 2012, 107, 1566–1569. [Google Scholar] [CrossRef] [PubMed]
- Sugawara, T.; Baskaran, V.; Tsuzuki, W.; Nagao, A. Brown Algae Fucoxanthin Is Hydrolyzed to Fucoxanthinol during Absorption by Caco-2 Human Intestinal Cells and Mice. J. Nutr. 2002, 132, 946–951. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Wu, H.; Wen, H.; Fang, H.; Hong, Z.; Yi, R.; Liu, R. Simultaneous Determination of Fucoxanthin and Its Deacetylated Metabolite Fucoxanthinol in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry. Mar. Drugs 2015, 13, 6521–6536. [Google Scholar] [CrossRef]
- Sachindra, N.M.; Sato, E.; Maeda, H.; Hosokawa, M.; Niwano, Y.; Kohno, M.; Miyashita, K. Radical Scavenging and Singlet Oxygen Quenching Activity of Marine Carotenoid Fucoxanthin and Its Metabolites. J. Agric. Food Chem. 2007, 55, 8516–8522. [Google Scholar] [CrossRef]
- Maoka, T. Carotenoids in Marine Animals. Mar. Drugs 2011, 9, 278–293. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Liu, L.; Sun, P.; Zhang, Y.; Wu, T.; Sun, H.; Cheng, K.-W.; Chen, F. Fucoxanthinol from the Diatom Nitzschia Laevis Ameliorates Neuroinflammatory Responses in Lipopolysaccharide-Stimulated BV-2 Microglia. Mar. Drugs 2020, 18, 116. [Google Scholar] [CrossRef] [PubMed]
- Jin, W.; Yang, L.; Yi, Z.; Fang, H.; Chen, W.; Hong, Z.; Zhang, Y.; Zhang, G.; Li, L. Anti-Inflammatory Effects of Fucoxanthinol in LPS-Induced RAW264.7 Cells through the NAAA-PEA Pathway. Mar. Drugs 2020, 18, 222. [Google Scholar] [CrossRef] [PubMed]
- Taira, J.; Sonamoto, M.; Uehara, M. Dual Biological Functions of a Cytoprotective Effect and Apoptosis Induction by Bioavailable Marine Carotenoid Fucoxanthinol through Modulation of the Nrf2 Activation in RAW264.7 Macrophage Cells. Mar. Drugs 2017, 15, 305. [Google Scholar] [CrossRef] [PubMed]
- Pruccoli, L.; Morroni, F.; Sita, G.; Hrelia, P.; Tarozzi, A. Esculetin as a Bifunctional Antioxidant Prevents and Counteracts the Oxidative Stress and Neuronal Death Induced by Amyloid Protein in SH-SY5Y Cells. Antioxidants 2020, 9, 551. [Google Scholar] [CrossRef] [PubMed]
- de Freitas Silva, M.; Tardelli Lima, E.; Pruccoli, L.; Castro, N.; Guimarães, M.; da Silva, F.; Fonseca Nadur, N.; de Azevedo, L.; Kümmerle, A.; Guedes, I.; et al. Design, Synthesis and Biological Evaluation of Novel Triazole N-acylhydrazone Hybrids for Alzheimer’s Disease. Molecules 2020, 25, 3165. [Google Scholar] [CrossRef] [PubMed]
- Pruccoli, L.; Breda, C.; Teti, G.; Falconi, M.; Giorgini, F.; Tarozzi, A. Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington’s Disease Models. Pharmaceuticals 2021, 14, 1044. [Google Scholar] [CrossRef] [PubMed]
- Cristancho Ortiz, C.J.; de Freitas Silva, M.; Pruccoli, L.; Fonseca Nadur, N.; de Azevedo, L.L.; Kümmerle, A.E.; Guedes, I.A.; Dardenne, L.E.; Leomil Coelho, L.F.; Guimarães, M.J.; et al. Design, synthesis, and biological evaluation of new thalidomide–donepezil hybrids as neuroprotective agents targeting cholinesterases and neuroinflammation. RSC Med. Chem. 2022, 13, 568–584. [Google Scholar] [CrossRef] [PubMed]
- Di Martino, R.M.C.; Pruccoli, L.; Bisi, A.; Gobbi, S.; Rampa, A.; Martinez, A.; Pérez, C.; Martinez-Gonzalez, L.; Paglione, M.; Di Schiavi, E.; et al. Novel Curcumin-Diethyl Fumarate Hybrid as a Dualistic GSK-3β Inhibitor/Nrf2 Inducer for the Treatment of Parkinson’s Disease. ACS Chem. Neurosci. 2020, 11, 2728–2740. [Google Scholar] [CrossRef]
- Heo, S.-J.; Jeon, Y.-J. Protective effect of fucoxanthin isolated from Sargassum siliquastrum on UV-B induced cell damage. J. Photochem. Photobiol. B Biol. 2009, 95, 101–107. [Google Scholar] [CrossRef]
- Pangestuti, R.; Kim, S.-K. Neuroprotective Effects of Marine Algae. Mar. Drugs 2011, 9, 803–818. [Google Scholar] [CrossRef]
- Bano, S.; Parihar, M.S. Reduction of lipid peroxidation in different brain regions by a combination of alpha-tocopherol and ascorbic acid. J. Neural Transm. 1997, 104, 1277–1286. [Google Scholar] [CrossRef] [PubMed]
- Aoyama, K. Glutathione in the Brain. Int. J. Mol. Sci. 2021, 22, 5010. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.-S.; Lu, Y.; Tao, T.; Wang, H.; Liu, G.-J.; Liu, X.-Z.; Liu, C.; Xia, D.-Y.; Hang, C.-H.; Li, W. Fucoxanthin Mitigates Subarachnoid Hemorrhage-Induced Oxidative Damage via Sirtuin 1-Dependent Pathway. Mol. Neurobiol. 2020, 57, 5286–5298. [Google Scholar] [CrossRef]
- Ravi Kumar, S.; Narayan, B.; Kizawa, Y.; Hosokawa, M.; Miyashita, K. Does squalene alter the antioxidant potential of astaxanthin and fucoxanthinol? In vitro evidence in RAW 264.7 cells, a murine macrophage. J. Food Sci. Technol. 2016, 53, 2139–2143. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, T.; Sherratt, P.J.; Pickett, C.B. Regulatory Mechanisms Controlling Gene Expression Mediated by the Antioxidant Response Element. Annu. Rev. Pharmacol. Toxicol. 2003, 43, 233–260. [Google Scholar] [CrossRef]
- Singhal, S.S.; Singh, S.P.; Singhal, P.; Horne, D.; Singhal, J.; Awasthi, S. Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling. Toxicol. Appl. Pharmacol. 2015, 289, 361–370. [Google Scholar] [CrossRef]
- Wu, W.; Han, H.; Liu, J.; Tang, M.; Wu, X.; Cao, X.; Zhao, T.; Lu, Y.; Niu, T.; Chen, J.; et al. Fucoxanthin Prevents 6-OHDA-Induced Neurotoxicity by Targeting Keap1. Oxid. Med. Cell. Longev. 2021, 2021, 1–14. [Google Scholar] [CrossRef]
- Wei, J.; Mou, C.; Bao, Y.; Xie, Y.; Jin, H.; Shen, H.; Zhou, W.; Zhang, J.; He, S.; Chen, B.; et al. Fucoxanthin alleviates methamphetamine-induced neurotoxicity possibly via the inhibition of interaction between Keap1 and Nrf2. J. Funct. Foods 2021, 86, 104713. [Google Scholar] [CrossRef]
- Blum, D.; Torch, S.; Lambeng, N.; Nissou, M.-F.; Benabid, A.-L.; Sadoul, R.; Verna, J.-M. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: Contribution to the apoptotic theory in Parkinson’s disease. Prog. Neurobiol. 2001, 65, 135–172. [Google Scholar] [CrossRef]
- Nutini, A. Amyloid oligomers and their membrane toxicity—A perspective study. Prog. Biophys. Mol. Biol. 2024, 187, 9–20. [Google Scholar] [CrossRef]
- Katayama, S.; Ogawa, H.; Nakamura, S. Apricot Carotenoids Possess Potent Anti-amyloidogenic Activity in Vitro. J. Agric. Food Chem. 2011, 59, 12691–12696. [Google Scholar] [CrossRef]
- Tarozzi, A.; Morroni, F.; Merlicco, A.; Hrelia, S.; Angeloni, C.; Cantelli-Forti, G.; Hrelia, P. Sulforaphane as an inducer of glutathione prevents oxidative stress-induced cell death in a dopaminergic-like neuroblastoma cell line. J. Neurochem. 2009, 111, 1161–1171. [Google Scholar] [CrossRef]
- Ikeda, K.; Kitamura, A.; Machida, H.; Watanabe, M.; Negishi, H.; Hiraoka, J.; Nakano, T. Effect of Undaria pinnatifida (Wakame) on the development of cerebrovascular diseases in stroke-prone spontaneously hypertensive rats. Clin. Exp. Pharmacol. Physiol. 2003, 30, 44–48. [Google Scholar] [CrossRef]
- Martini, D.; Negrini, L.; Marino, M.; Riso, P.; Del Bo, C.; Porrini, M. What Is the Current Direction of the Research on Carotenoids and Human Health? An Overview of Registered Clinical Trials. Nutrients 2022, 14, 1191. [Google Scholar] [CrossRef]
- Din, N.A.; Mohd Alayudin, A.S.; Sofian-Seng, N.S.; Rahman, H.A.; Mohd Razali, N.S.; Lim, S.J.; Wan Mustapha, W.A. Brown Algae as Functional Food Source of Fucoxanthin: A Review. Foods 2022, 11, 2235. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Pruccoli, L.; Balducci, M.; Pagliarani, B.; Tarozzi, A. Antioxidant and Neuroprotective Effects of Fucoxanthin and Its Metabolite Fucoxanthinol: A Comparative In Vitro Study. Curr. Issues Mol. Biol. 2024, 46, 5984-5998. https://doi.org/10.3390/cimb46060357
Pruccoli L, Balducci M, Pagliarani B, Tarozzi A. Antioxidant and Neuroprotective Effects of Fucoxanthin and Its Metabolite Fucoxanthinol: A Comparative In Vitro Study. Current Issues in Molecular Biology. 2024; 46(6):5984-5998. https://doi.org/10.3390/cimb46060357
Chicago/Turabian StylePruccoli, Letizia, Martina Balducci, Barbara Pagliarani, and Andrea Tarozzi. 2024. "Antioxidant and Neuroprotective Effects of Fucoxanthin and Its Metabolite Fucoxanthinol: A Comparative In Vitro Study" Current Issues in Molecular Biology 46, no. 6: 5984-5998. https://doi.org/10.3390/cimb46060357