Neuroprotective Effects of Bioavailable Polyphenol-Derived Metabolites against Oxidative Stress-Induced Cytotoxicity in Human Neuroblastoma SH-SY5Y Cells
Open accessAbstract
Abstract Oxidative stress is involved in cell death in neurodegenerative diseases. Dietary polyphenols can exert health benefits, but their direct effects on neuronal cells are debatable because most phenolics are metabolized and do not reach the brain as they occur in the dietary sources. Herein, we evaluate the effects of a panel of bioavailable polyphenols and derived metabolites at physiologically relevant conditions against H2O2-induced apoptosis in human neuroblastoma SH-SY5Y cells. Among the 19 metabolites tested, 3,4-dihydroxyphenylpropionic acid, 3,4-dihydroxyphenylacetic acid, gallic acid, ellagic acid, and urolithins prevented neuronal apoptosis via attenuation of ROS levels, increased REDOX activity, and decreased oxidative stress-induced apoptosis by preventing the caspase-3 activation via the mitochondrial apoptotic pathway in SH-SY5Y cells. This suggests that dietary sources containing the polyphenol precursors of these molecules such as cocoa, berries, walnuts, and tea could be potential functional foods to reduce oxidative stress associated with the onset and progress of neurodegenerative diseases.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The human neuroblastoma SH-SY5Y is among the most used cell lines, a subclone of the parental neuronal line SK-N-SH, which originated in 1970 from a biopsy metastatic tumor.
“The human neuroblastoma SH-SY5Y is among the most used cell lines [131,136,137,138,139,140,141,142], a subclone of a parental neuronal line SK-N-SH, which originated in 1970 from a biopsy metastatic tumor.”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [138]
Cites
Uttara, B., Singh, A., Zamboni, P., & Mahajan, R. (2009) · Current Neuropharmacology · doi:10.2174/157015909787602823 · Cited by 3,378 · see citing works
Del Rio, D., Rodriguez-Mateos, A., Spencer, J. P. E., Tognolini, M., Borges, G., & Crozier, A. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4581 · Cited by 2,601 · see citing works
Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease
Wang, X., Wang, W., Li, L., Perry, G., Lee, H.-G., & Zhu, X. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.10.015 · Cited by 1,357 · see citing works
Interaction between Phenolics and Gut Microbiota: Role in Human Health
Selma, M. V., Espín, J. C., & Tomás-Barberán, F. A. (2009) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf902107d · Cited by 1,324 · see citing works
Self-citationA randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease
Turner, R. S., Thomas, R. G., Craft, S., van Dyck, C. H., Mintzer, J. E., Reynolds, B., Brewer, J. B., Rissman, R. A., Raman, R., Aisen, P. S. S., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000002035 · Cited by 752 · see citing works
Monagas, M., Urpí-Sardà, M., Sánchez‐Patán, F., Llorach, R., Garrido, I., Gómez‐Cordovés, C., Andrés‐Lacueva, C., & Bartolomé, B. (2010) · Food & Function · doi:10.1039/c0fo00132e · Cited by 600 · see citing works
Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory
Andrés‐Lacueva, C., Shukitt‐Hale, B., Galli, R. L., Jáuregui, O., Lamuela-Raventós, R. M., & Joseph, J. A. (2005) · Nutritional Neuroscience · doi:10.1080/10284150500078117 · Cited by 564 · see citing works
Fruit and Vegetable Juices and Alzheimer’s Disease: The Kame Project
Dai, Q., Borenstein, A. R., Wu, Y., Jackson, J. C., & Larson, E. B. (2006) · The American Journal of Medicine · doi:10.1016/j.amjmed.2006.03.045 · Cited by 524 · see citing works
Flavonoid Intake and Cognitive Decline over a 10-Year Period
Letenneur, L., Proust‐Lima, C., Gouge, A. L., Dartigues, J. F., & Barberger‐Gateau, P. (2007) · American Journal of Epidemiology · doi:10.1093/aje/kwm036 · Cited by 484 · see citing works
Tomás‐Barberán, F. A., González‐Sarrías, A., García‐Villalba, R., Núñez‐Sánchez, M. A., Selma, M. V., García‐Conesa, M. T., & Espín, J. C. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500901 · Cited by 465 · see citing works
Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence
Tomé‐Carneiro, J., Larrosa, M., González‐Sarrías, A., Tomás-Barberán, F. A., García‐Conesa, M., & Espı́n, J. C. (2013) · Current Pharmaceutical Design · doi:10.2174/13816128113199990407 · Cited by 451 · see citing works
Singh, M., Arseneault, M., Sanderson, J. T., Murthy, V., & Ramassamy, C. (2008) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf0735073 · Cited by 438 · see citing works
Hartman, R. E., Shah, A., Fagan, A. M., Schwetye, K. E., Parsadanian, M., Schulman, R. N., Finn, M. B., & Holtzman, D. M. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.08.006 · Cited by 358 · see citing works
Neuroinflammation: Modulation by flavonoids and mechanisms of action
Spencer, J. P. E., Vafeiadou, K., Williams, R. J., & Vauzour, D. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.10.016 · Cited by 315 · see citing works
Ferruzzi, M. G., Lobo, J., Janle, E. M., Cooper, B. R., Simon, J. E., Wu, Q., Welch, C., Ho, L., Weaver, C. M., & Pasinetti, G. M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1135 · Cited by 250 · see citing works
Daglia, M., Lorenzo, A. D., Nabavi, S. F., Talas, Z., & Nabavi, S. F. (2014) · Current Pharmaceutical Biotechnology · doi:10.2174/138920101504140825120737 · Cited by 244 · see citing works
Tabner, B. J., El‐Agnaf, O. M. A., Turnbull, S., German, M. J., Paleologou, K. E., Hayashi, Y., Cooper, L. J., Fullwood, N. J., & Allsop, D. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500238200 · Cited by 241 · see citing works
Yuan, T., Ma, H., Liu, W., Niesen, D. B., Shah, N., Crews, R., Rose, K. N., Vattem, D. A., & Seeram, N. P. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00260 · Cited by 219 · see citing works
Nutrition and the Risk of Alzheimer's Disease
Hu, N., Yu, J., Tan, L., Wang, Y., Sun, L., & Tan, L. (2013) · BioMed Research International · doi:10.1155/2013/524820 · Cited by 212 · see citing works
Neuronal Life-and-Death Signaling, Apoptosis, and Neurodegenerative Disorders
Mattson, M. P. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.1997 · Cited by 211 · see citing works
Reactive oxygen species induce different cell death mechanisms in cultured neurons
Valencia, A., & Morán, J. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.02.013 · Cited by 204 · see citing works
Oxidative stress and Alzheimer’s disease: dietary polyphenols as potential therapeutic agents
Darvesh, A. S., Carroll, R. T., Bishayee, A., Geldenhuys, W. J., & der Schyf, C. J. V. (2010) · Expert Review of Neurotherapeutics · doi:10.1586/ern.10.42 · Cited by 203 · see citing works
Oxidative Stress in Alzheimer’s Disease: Are We Connecting the Dots?
Rosini, M., Simoni, E., Milelli, A., Minarini, A., & Melchiorre, C. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400970m · Cited by 202 · see citing works
Antiglycative and neuroprotective activity of colon‐derived polyphenol catabolites
Verzelloni, E., Pellacani, C., Tagliazucchi, D., Tagliaferri, S., Calani, L., Costa, L. G., Brighenti, F., Borges, G., Crozier, A., Conte, A., et al. (2011) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201000525 · Cited by 190 · see citing works
González‐Sarrías, A., Garcı́a-Villalba, R., Núñez‐Sánchez, M. Á., Tomé‐Carneiro, J., Zafrilla, P., Mulero, J., Tomás-Barberán, F. A., & Espı́n, J. C. (2015) · Journal of Functional Foods · doi:10.1016/j.jff.2015.09.019 · Cited by 184 · see citing works
Singh, N., Agrawal, M., & Doré, S. (2013) · ACS Chemical Neuroscience · doi:10.1021/cn400094w · Cited by 184 · see citing works
Urpí-Sardà, M., Monagas, M., Khan, N., Llorach, R., Lamuela-Raventós, R. M., Jáuregui, O., Estruch, R., Izquierdo-Pulido, M., & Andrés‐Lacueva, C. (2009) · Journal of Chromatography A · doi:10.1016/j.chroma.2009.07.058 · Cited by 182 · see citing works
Chocolate and the brain: Neurobiological impact of cocoa flavanols on cognition and behavior
Sokolov, A. N., Pavlova, M. A., Klosterhalfen, S., & Enck, P. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.06.013 · Cited by 178 · see citing works
Fate of Microbial Metabolites of Dietary Polyphenols in Rats: Is the Brain Their Target Destination?
Gasperotti, M., Passamonti, S., Tramer, F., Masuero, D., Guella, G., Mattivi, F., & Vrhovšek, U. (2015) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00051 · Cited by 163 · see citing works
Health benefits of walnut polyphenols: An exploration beyond their lipid profile
Sánchez‐González, C., Ciudad, C. J., Noé, V., & Izquierdo-Pulido, M. (2015) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2015.1126218 · Cited by 160 · see citing works
Kim, M., Seong, A., Yoo, J., Jin, C., Lee, Y., Kim, Y. J., Lee, J., Jun, W. J., & Yoon, H. (2011) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201100262 · Cited by 155 · see citing works
Rojanathammanee, L., Puig, K. L., & Combs, C. K. (2013) · Journal of Nutrition · doi:10.3945/jn.112.169516 · Cited by 150 · see citing works
Pandareesh, M. D., Mythri, R. B., & Bharath, M. M. S. (2015) · Neurochemistry International · doi:10.1016/j.neuint.2015.07.003 · Cited by 137 · see citing works
Metabolites and tissue distribution of resveratrol in the pig
Azorín‐Ortuño, M., Yáñez-Gascón, M. J., Vallejo, F., Pallarés, F. J., Larrosa, M., Lucas, R., Morales, J. C., Tomás-Barberán, F. A., García‐Conesa, M., & Espı́n, J. C. (2011) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201100140 · Cited by 135 · see citing works
Beking, K., & Vieira, A. V. (2010) · Public Health Nutrition · doi:10.1017/s1368980009992990 · Cited by 110 · see citing works
Fornasaro, S., Žiberna, L., Gasperotti, M., et al. (2016) · Scientific Reports · doi:10.1038/srep22815 · Cited by 91 · see citing works
Braidy, N., Jugder, B., Poljak, A., Jayasena, T., Mansour, H., Nabavi, S. M., Sachdev, P. S., & Grant, R. (2016) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026616666160204121431 · Cited by 89 · see citing works
Resveratrol attenuates oxidative-induced DNA damage in C6 Glioma cells
Quincozes‐Santos, A., Andreazza, A. C., Nardin, P., et al. (2007) · NeuroToxicology · doi:10.1016/j.neuro.2007.03.008 · Cited by 84 · see citing works
Yan, L., Yin, P., Ma, C., & Liu, Y. (2014) · Molecules · doi:10.3390/molecules191118923 · Cited by 75 · see citing works
González‐Sarrías, A., Núñez‐Sánchez, M. Á., Garcı́a-Villalba, R., Tomás-Barberán, F. A., & Espı́n, J. C. (2015) · European Journal of Nutrition · doi:10.1007/s00394-015-1131-7 · Cited by 72 · see citing works
Park, H. R., Lee, H., Park, H., Jeon, J. W., Cho, W.-K., & Ma, J. Y. (2015) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-015-0679-3 · Cited by 68 · see citing works
Neuroprotective effects of orientin on hydrogen peroxide-induced apoptosis in SH-SY5Y cells
LAW, B. N. T., Ling, A. P. K., Koh, R. Y., Chye, S. M., & Wong, Y. P. (2013) · Molecular Medicine Reports · doi:10.3892/mmr.2013.1878 · Cited by 66 · see citing works
The Effects of Ellagic Acid upon Brain Cells: A Mechanistic View and Future Directions
de Oliveira, M. R. (2016) · Neurochemical Research · doi:10.1007/s11064-016-1853-9 · Cited by 63 · see citing works
de Almeida, L. M. V., Leite, M. C., Thomazi, A. P., Battú, C. E., Nardin, P., Tortorelli, L. S., Zanotto, C., Posser, T., Wofchuk, S. T., Leal, R. B., et al. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.09.006 · Cited by 62 · see citing works
Neuroprotective properties of Spanish red wine and its isolated polyphenols on astrocytes
Martín, S., González‐Burgos, E., Carretero, M. E., et al. (2011) · Food Chemistry · doi:10.1016/j.foodchem.2011.02.074 · Cited by 56 · see citing works
Ahmed, A., Subaiea, M., Eid, A., Li, L., Seeram, P., & Zawia, H. (2014) · Current Alzheimer Research · doi:10.2174/1567205011666141001115348 · Cited by 47 · see citing works
Panickar, K. S., & Jang, S. (2013) · Recent Patents on Food Nutrition & Agriculture · doi:10.2174/1876142911305020003 · Cited by 43 · see citing works
Organic silicon protects human neuroblastoma SH-SY5Y cells against hydrogen peroxide effects
Garcimartín, A., Merino, J. J., González, M. P., Sánchez-Reus, M. I., Sánchez-Muniz, F. J., Bastida, S., & Benedı́, J. (2014) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-14-384 · Cited by 34 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The gut microbiota: a key factor in the therapeutic effects of (poly)phenols
Espín, J. C., González-Sarrías, A., & Tomás-Barberán, F. A. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.04.033 · Cited by 603 · see citing works
Sharifi-Rad, J., Rapposelli, S., Sestito, S., Herrera-Bravo, J., Arancibia-Diaz, A., Salazar, L. A., Yeskaliyeva, B., Beyatli, A., Leyva-Gómez, G., González-Contreras, C., et al. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12091515 · Cited by 125 · see citing works
- Authors
- González-Sarrías, A., Núñez-Sánchez, M. A., Tomás-Barberán, F. A., & Espín, J. C.
- Affiliations
- CEBAS-CSIC , , P.O. Box 164, , ,
- Venue
- Journal of Agricultural and Food Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-11-14
- Volume
- 65
- Issue
- 4
- Pages
- 752-758
- ISSN
- 0021-8561 (ISSN-L)
- 1520-5118
- OpenAlex
- W2556479552
- Cited by
- 174
- References
- 48
- Citations by year
- 2026: 15 · 2025: 12 · 2024: 15 · 2023: 12 · 2022: 28 · 2021: 24 · 2020: 21 · 2019: 17 · 2018: 19 · 2017: 11
- FWCI
- 12.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Agricultural and Food Chemistry (publishedVersion, other-oa)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Ministerio de Economía y Competitividad (NA)
- Consejo Superior de Investigaciones Científicas (201370E068)
- Seventh Framework Programme (312090)
- Comisión Interministerial de Ciencia y Tecnología (AGL2011-22447, AGL2015-64124-R)
- Topics
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Health Sciences › Nursing › Nutrition and Dietetics › Pomegranate: compositions and health benefits
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- polyphenol metabolites, oxidative stress, neuroprotection, apoptosis, SH-SY5Y cells, hydrogen peroxide, reactive oxygen species, caspase-3, mitochondrial apoptosis, DOPAC, gallic acid, ellagic acid, urolithins, neurodegenerative diseases, functional foods, dietary polyphenols
- MeSH terms
- Humans, Neurons, Molecular Structure, Apoptosis, Oxidative Stress, Neuroprotective Agents, Cell Line, Tumor, Caspase 3, Polyphenols
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review