{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:27:03Z","timestamp":1791847623032,"version":"4.3.4"},"reference-count":215,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cPiano di incentivi per la Ricerca, Linea Intervento 2 PIACERI, 2020\u20132022\u201d, University of Catania, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished\/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction\/loss. A strategy is necessary to protect hair cells and XIII cranial\/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental\/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose\u2013response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose\u2013response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and\/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose\u2013response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial\/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy.<\/jats:p>","DOI":"10.3390\/medicina59112045","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T10:32:32Z","timestamp":1700476352000},"page":"2045","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Polyphenols in Inner Ear Neurobiology, Health and Disease: From Bench to Clinics"],"prefix":"10.3390","volume":"59","author":[{"given":"Naomi","family":"Osakabe","sequence":"first","affiliation":[{"name":"Department of Bioscience and Engineering, Shibaura Institute Technology, Saitama 337-8570, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Modafferi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura","family":"Ontario","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Rampulla","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Zimbone","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rita","family":"Migliore","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman","family":"Fritsch","sequence":"additional","affiliation":[{"name":"NAM Institute, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5910-2832","authenticated-orcid":false,"given":"Ali S.","family":"Abdelhameed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Maiolino","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical Advanced Technologies \u201cG. F. Ingrassia\u201d, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9291-6969","authenticated-orcid":false,"given":"Gabriella","family":"Lupo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelina Daniela","family":"Anfuso","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Genovese","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child and Adult Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Monzani","sequence":"additional","affiliation":[{"name":"Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37100 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Ern\u00e4hrungswissenschaft, Justus Liebig Universitat Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Morrill I, N344, University of Massachusetts, Amherst, MA 01003, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Martin","family":"Vabulas","sequence":"additional","affiliation":[{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin, Institute of Biochemistry, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0478-985X","authenticated-orcid":false,"given":"Vittorio","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ferlito, S., Fadda, G., Lechien, J.R., Cammaroto, G., Bartel, R., Borello, A., Cavallo, G., Piccinini, F., La Mantia, I., and Cocuzza, S. (2022). Type 1 tympanoplasty outcomes between cartilage and temporal fascia grafts: A long-term retrospective study. J. Clin. Med., 11.","DOI":"10.3390\/jcm11237000"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ald\u00e8, M., Cantarella, G., Zanetti, D., Pignataro, L., La Mantia, I., Maiolino, L., Ferlito, S., Di Mauro, P., Cocuzza, S., and Lechien, J.R. (2023). Autosomal dominant non-syndromic hearing loss (dfna): A comprehensive narrative review. Biomedicines, 11.","DOI":"10.3390\/biomedicines11061616"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuroscience.2013.04.001","article-title":"Gingko biloba extracts protect auditory hair cells from cisplatin-induced ototoxicity by inhibiting perturbation of gap junctional intercellular communication","volume":"244","author":"Choi","year":"2013","journal-title":"Neuroscience"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/ptr.5572","article-title":"Ginkgo biloba extract attenuates oxidative stress and apoptosis in mouse cochlear neural stem cells","volume":"30","author":"Wang","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s10571-015-0180-z","article-title":"Ginkgo Biloba Extract Enhances Differentiation and Performance of Neural Stem Cells in Mouse Cochlea","volume":"35","author":"Wang","year":"2015","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1007\/s11064-014-1311-5","article-title":"(\u2212)-Epigallocatechin Gallate Protects against Cerebral Ischemia-Induced Oxidative Stress via Nrf2\/ARE Signaling","volume":"39","author":"Han","year":"2014","journal-title":"Neurochem. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1002\/lary.21756","article-title":"Korean red ginseng prevents gentamicin-induced hearing loss in rats","volume":"121","author":"Choung","year":"2011","journal-title":"Laryngoscope"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ijporl.2016.10.008","article-title":"Comparison of the effects of lipoic acid and glutathione against cisplatin-induced ototoxicity in auditory cells","volume":"91","author":"Koo","year":"2016","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3109\/03602532.2014.1003649","article-title":"Flavonoid interactions during digestion, absorption, distribution and metabolism: A sequential structure\u2013activity\/property relationship-based approach in the study of bioavailability and bioactivity","volume":"47","author":"Gonzales","year":"2015","journal-title":"Drug Metab. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Boas, S.M., Joyce, K.L., and Cowell, R.M. (2021). The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention. Antioxidants, 11.","DOI":"10.3390\/antiox11010008"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/jnc.13581","article-title":"Dissecting the role of redox signaling in neuronal development","volume":"137","author":"Urrutia","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1124\/jpet.116.237503","article-title":"Oxidative Stress and the Central Nervous System","volume":"360","author":"Salim","year":"2017","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.neuropharm.2013.11.004","article-title":"NRF2-regulation in brain health and disease: Implication of cerebral inflammation","volume":"79","author":"Sandberg","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9926","DOI":"10.1073\/pnas.91.21.9926","article-title":"Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2\/AP1 repeat of the beta-globin locus control region","volume":"91","author":"Moi","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.molcel.2009.04.029","article-title":"Direct Interaction between Nrf2 and p21Cip1\/WAF1 Upregulates the Nrf2-Mediated Antioxidant Response","volume":"34","author":"Chen","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_16","first-page":"e17","article-title":"The Nrf2\u2013ARE cytoprotective pathway in astrocytes. Expert Rev","volume":"11","author":"Vargas","year":"2009","journal-title":"Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1759091419899782","DOI":"10.1177\/1759091419899782","article-title":"NRF2 as a Therapeutic Target in Neurodegenerative Diseases","volume":"12","author":"Brandes","year":"2020","journal-title":"ASN Neuro"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cordaro, M., Salinaro, A.T., Siracusa, R., D\u2019amico, R., Impellizzeri, D., Scuto, M., Ontario, M.L., Cuzzocrea, S., Di Paola, R., and Fusco, R. (2021). Key Mechanisms and Potential Implications of Hericium erinaceus in NLRP3 Inflammasome Activation by Reactive Oxygen Species during Alzheimer\u2019s Disease. Antioxidants, 10.","DOI":"10.3390\/antiox10111664"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1096\/fj.201901584RR","article-title":"Effect of N-palmitoylethanolamine-oxazoline on comorbid neuropsychiatric disturbance associated with inflammatory bowel disease","volume":"34","author":"Cordaro","year":"2020","journal-title":"FASEB J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cordaro, M., Salinaro, A.T., Siracusa, R., D\u2019amico, R., Impellizzeri, D., Scuto, M., Ontario, M.L., Crea, R., Cuzzocrea, S., and Di Paola, R. (2021). Hidrox\u00ae Roles in Neuroprotection: Biochemical Links between Traumatic Brain Injury and Alzheimer\u2019s Disease. Antioxidants, 10.","DOI":"10.3390\/antiox10050818"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cordaro, M., Salinaro, A.T., Siracusa, R., D\u2019Amico, R., Impellizzeri, D., Scuto, M., Ontario, M.L., Interdonato, L., Crea, R., and Fusco, R. (2021). Hidrox\u00ae and Endometriosis: Biochemical Evaluation of Oxidative Stress and Pain. Antioxidants, 10.","DOI":"10.3390\/antiox10050720"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fusco, R., Salinaro, A.T., Siracusa, R., D\u2019amico, R., Impellizzeri, D., Scuto, M., Ontario, M.L., Crea, R., Cordaro, M., and Cuzzocrea, S. (2021). Hidrox\u00ae Counteracts Cyclophosphamide-Induced Male Infertility through NRF2 Pathways in a Mouse Model. Antioxidants, 10.","DOI":"10.3390\/antiox10050778"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Brunetti, G., Di Rosa, G., Scuto, M., Leri, M., Stefani, M., Schmitz-Linneweber, C., Calabrese, V., and Saul, N. (2020). Healthspan Maintenance and Prevention of Parkinson\u2019s-like Phenotypes with Hydroxytyrosol and Oleuropein Aglycone in C. elegans. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072588"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Di Rosa, G., Brunetti, G., Scuto, M., Salinaro, A.T., Calabrese, E.J., Crea, R., Schmitz-Linneweber, C., Calabrese, V., and Saul, N. (2020). Healthspan Enhancement by Olive Polyphenols in C. elegans Wild Type and Parkinson\u2019s Models. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113893"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Jembrek, M.J., Or\u0161oli\u0107, N., Mandi\u0107, L., Sad\u017eak, A., and \u0160egota, S. (2021). Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-\u03baB and p53 Pathways in Neurodegeneration. Antioxidants, 10.","DOI":"10.3390\/antiox10101628"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhou, Z.D., Xie, S.P., Saw, W.T., Ho, P.G.H., Wang, H.Y., Zhou, L., Zhao, Y., and Tan, E.K. (2019). The Therapeutic Implications of Tea Polyphenols Against Dopamine (DA) Neuron Degeneration in Parkinson\u2019s Disease (PD). Cells, 8.","DOI":"10.3390\/cells8080911"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1002\/tox.22844","article-title":"Di (2-ethylhexyl) phthalate targets the thioredoxin system and the oxidative branch of the pentose phosphate pathway in liver of Balb\/c mice","volume":"35","author":"Amara","year":"2020","journal-title":"Environ. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Amara, I., Scuto, M., Zappal\u00e0, A., Ontario, M.L., Petralia, A., Abid-Essefi, S., Maiolino, L., Signorile, A., Salinaro, A.T., and Calabrese, V. (2020). Hericium erinaceus Prevents DEHP-Induced Mitochondrial Dysfunction and Apoptosis in PC12 Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062138"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"D\u2019amico, R., Salinaro, A.T., Fusco, R., Cordaro, M., Impellizzeri, D., Scuto, M., Ontario, M.L., Dico, G.L., Cuzzocrea, S., and Di Paola, R. (2021). Hericium erinaceus and Coriolus versicolor Modulate Molecular and Biochemical Changes after Traumatic Brain Injury. Antioxidants, 10.","DOI":"10.3390\/antiox10060898"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Scuto, M., Salinaro, A.T., Modafferi, S., Polimeni, A., Pfeffer, T., Weigand, T., Calabrese, V., Schmitt, C.P., and Peters, V. (2020). Carnosine Activates Cellular Stress Response in Podocytes and Reduces Glycative and Lipoperoxidative Stress. Biomedicines, 8.","DOI":"10.3390\/biomedicines8060177"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3389\/fphar.2014.00120","article-title":"Osteoporosis and alzheimer pathology: Role of cellular stress response and hormetic redox signaling in aging and bone remodeling","volume":"5","author":"Cornelius","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1742-4933-10-15","article-title":"Stress responses, vitagenes and hormesis as critical determinants in aging and longevity: Mitochondria as a \u201cchi\u201d","volume":"10","author":"Cornelius","year":"2013","journal-title":"Immun. Ageing"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Amara, I., Ontario, M.L., Scuto, M., Dico, G.M.L., Sciuto, S., Greco, V., Abid-Essefi, S., Signorile, A., Salinaro, A.T., and Calabrese, V. (2021). Moringa oleifera Protects SH-SY5YCells from DEHP-Induced Endoplasmic Reticulum Stress and Apoptosis. Antioxidants, 10.","DOI":"10.3390\/antiox10040532"},{"key":"ref_34","first-page":"129","article-title":"Cellular stress response, redox status, and vitagenes in glaucoma: A systemic oxidant disorder linked to Alzheimer\u2019s disease","volume":"5","author":"Salinaro","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1002\/jnr.24244","article-title":"Hormetic approaches to the treatment of Parkinson\u2019s disease: Perspectives and possibilities","volume":"96","author":"Calabrese","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/bs.irn.2020.03.024","article-title":"Hormesis: A potential strategic approach to the treatment of neurodegenerative disease","volume":"155","author":"Calabrese","year":"2020","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3389\/fnins.2018.00466","article-title":"Targeting Nrf2 to Suppress Ferroptosis and Mitochondrial Dysfunction in Neurodegeneration","volume":"12","author":"Abdalkader","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.freeradbiomed.2015.07.147","article-title":"Nrf2\u2014A therapeutic target for the treatment of neurodegenerative diseases","volume":"88","author":"Johnson","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41573-018-0008-x","article-title":"Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases","volume":"18","author":"Cuadrado","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3050971","DOI":"10.1155\/2020\/3050971","article-title":"Nrf2 Ablation Promotes Alzheimer\u2019s Disease-Like Pathology in APP\/PS1 Transgenic Mice: The Role of Neuroinflammation and Oxidative Stress","volume":"2020","author":"Ren","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s11357-019-00107-w","article-title":"Nrf2 dysfunction and impaired cellular resilience to oxidative stressors in the aged vasculature: From increased cellular senescence to the pathogenesis of age-related vascular diseases","volume":"41","author":"Ungvari","year":"2019","journal-title":"GeroScience"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"964","DOI":"10.14336\/AD.2021.0511","article-title":"NRF2 Loss Accentuates Parkinsonian Pathology and Behavioral Dysfunction in Human \u03b1-Synuclein Overexpressing Mice","volume":"12","author":"Anandhan","year":"2021","journal-title":"Aging Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.pharmthera.2015.11.003","article-title":"Nrf2\u2013ARE pathway: An emerging target against oxidative stress and neuroinflammation in neurodegenerative diseases","volume":"157","author":"Buendia","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"111637","DOI":"10.1016\/j.mad.2022.111637","article-title":"Potential prevention and treatment of neurodegenerative disorders by olive polyphenols and hidrox","volume":"203","author":"Ontario","year":"2022","journal-title":"Mech. Ageing Dev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.freeradbiomed.2015.04.036","article-title":"The emerging role of Nrf2 in mitochondrial function","volume":"88","author":"Abramov","year":"2015","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.taap.2018.09.014","article-title":"Regulatory crosstalk between the oxidative stress-related transcription factor Nfe2l2\/Nrf2 and mitochondria","volume":"359","author":"Ryoo","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103413","DOI":"10.1016\/j.mcn.2019.103413","article-title":"Crosstalk between Nrf2 signaling and mitochondrial function in Parkinson\u2019s disease","volume":"101","author":"Ahuja","year":"2019","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1111\/febs.14607","article-title":"Determinants of Dopaminergic Neuron Loss in Parkinson\u2019s Disease","volume":"285","author":"Surmeier","year":"2018","journal-title":"FEBS J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"153676","DOI":"10.1016\/j.phymed.2021.153676","article-title":"The neuroprotective potential of carotenoids in vitro and in vivo","volume":"91","author":"Manochkumar","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Mattioli, R., Francioso, A., D\u2019erme, M., Trovato, M., Mancini, P., Piacentini, L., Casale, A.M., Wessjohann, L., Gazzino, R., and Costantino, P. (2019). Anti-Inflammatory Activity of A Polyphenolic Extract from Arabidopsis thaliana in In Vitro and In Vivo Models of Alzheimer\u2019s Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030708"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1179\/1476830515Y.0000000042","article-title":"Anthocyanin suppresses the toxicity of A\u03b2 deposits through diversion of molecular forms in in vitro and in vivo models of Alzheimer\u2019s disease","volume":"19","author":"Yamakawa","year":"2016","journal-title":"Nutr. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"234","DOI":"10.4103\/1673-5374.290879","article-title":"Potential therapeutic effects of polyphenols in Parkinson\u2019s disease: In vivo and in vitro pre-clinical studies","volume":"16","author":"Blandini","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"112226","DOI":"10.1016\/j.jep.2019.112226","article-title":"Efficacy of oral administration of licorice as an adjunct therapy on improving the symptoms of patients with Parkinson\u2019s disease, A randomized double blinded clinical trial","volume":"247","author":"Petramfar","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-019-0101-y","article-title":"The proteostasis network and its decline in ageing","volume":"20","author":"Hipp","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Tseng, C.-S., Chao, Y.-W., Liu, Y.-H., Huang, Y.-S., and Chao, H.-W. (2023). Dysregulated proteostasis network in neuronal diseases. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1075215"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1146\/annurev-biochem-060809-095203","article-title":"Regulation of HSF1 Function in the Heat Stress Response: Implications in Aging and Disease","volume":"80","author":"Anckar","year":"2011","journal-title":"Annu. Rev. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Siv\u00e9ry, A., Courtade, E., and Thommen, Q. (2016). A minimal titration model of the mammalian dynamical heat shock response. Phys. Biol., 13.","DOI":"10.1088\/1478-3975\/13\/6\/066008"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1021\/pr201151a","article-title":"Post-Translational Modification of Human Heat Shock Factors and Their Functions: A Recent Update by Proteomic Approach","volume":"11","author":"Xu","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1093\/hmg\/ddv445","article-title":"NEDD4-mediated HSF1 degradation underlies \u03b1-synucleinopathy","volume":"25","author":"Kim","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"14405","DOI":"10.1038\/ncomms14405","article-title":"Abnormal degradation of the neuronal stress-protective transcription factor HSF1 in Huntington\u2019s disease","volume":"8","author":"Burchfiel","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/nrm.2017.73","article-title":"Regulation of heat shock transcription factors and their roles in physiology and disease","volume":"19","author":"Burchfiel","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1038\/emboj.2010.225","article-title":"Heat shock factor 1 ameliorates proteotoxicity in cooperation with the transcription factor NFAT","volume":"29","author":"Hayashida","year":"2010","journal-title":"EMBO J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"34908","DOI":"10.1074\/jbc.M506288200","article-title":"Active HSF1 Significantly Suppresses Polyglutamine Aggregate Formation in Cellular and Mouse Models","volume":"280","author":"Fujimoto","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1091\/mbc.e11-04-0330","article-title":"Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation","volume":"22","author":"Shinkawa","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1007\/s11033-009-9623-2","article-title":"Dominant-positive HSF1 decreases alpha-synuclein level and alpha-synuclein-induced toxicity","volume":"37","author":"Liangliang","year":"2010","journal-title":"Mol. Biol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.brainres.2013.04.059","article-title":"Increased heat shock transcription factor 1 in the cerebellum reverses the deficiency of Purkinje cells in Alzheimer\u2019s disease","volume":"1519","author":"Jiang","year":"2013","journal-title":"Brain Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1523\/JNEUROSCI.0151-13.2014","article-title":"Hsp90 Chaperone Inhibitor 17-AAG Attenuates A\u03b2-Induced Synaptic Toxicity and Memory Impairment","volume":"34","author":"Chen","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5789","DOI":"10.1523\/JNEUROSCI.23-13-05789.2003","article-title":"High Threshold for Induction of the Stress Response in Motor Neurons Is Associated with Failure to Activate HSF1","volume":"23","author":"Batulan","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/978-3-031-14740-1_13","article-title":"Hsp70-hsp90 chaperone networking in protein-misfolding disease","volume":"101","author":"Prodromou","year":"2023","journal-title":"Subcell Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1089\/ars.2021.0055","article-title":"Cochlear Preconditioning as a Modulator of Susceptibility to Hearing Loss","volume":"36","author":"Harrison","year":"2022","journal-title":"Antioxid. Redox Signal."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1539\/joh.L8032","article-title":"Changes in Guinea Pig Cochlear Hair Cells after Sound Conditioning and Noise Exposure","volume":"50","author":"Zuo","year":"2008","journal-title":"J. Occup. Health"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8823785","DOI":"10.1155\/2020\/8823785","article-title":"Hsp70\/Bmi1-FoxO1-SOD Signaling Pathway Contributes to the Protective Effect of Sound Conditioning against Acute Acoustic Trauma in a Rat Model","volume":"2020","author":"Zhu","year":"2020","journal-title":"Neural Plast."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.molcel.2004.06.029","article-title":"Cellular Toxicity of Polyglutamine Expansion Proteins: Mechanism of Transcription Factor Deactivation","volume":"15","author":"Schaffar","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7841","DOI":"10.1073\/pnas.140202897","article-title":"Hsp70 and Hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils","volume":"97","author":"Muchowski","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"14733","DOI":"10.1074\/jbc.M413024200","article-title":"Heat Shock Protein 70 Inhibits \u03b1-Synuclein Fibril Formation via Preferential Binding to Prefibrillar Species","volume":"280","author":"Dedmon","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/372475a0","article-title":"Protein disaggregation mediated by heat-shock protein Hspl04","volume":"372","author":"Parsell","year":"1994","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0092-8674(00)81223-4","article-title":"Hsp104, Hsp70, and Hsp40: A Novel Chaperone System that Rescues Previously Aggregated Proteins","volume":"94","author":"Glover","year":"1998","journal-title":"Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nature14884","article-title":"Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation","volume":"524","author":"Nillegoda","year":"2015","journal-title":"Nature"},{"key":"ref_79","first-page":"489","article-title":"HSP40 proteins use class-specific regulation to drive HSP70 functional diversity","volume":"587","author":"Faust","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/s41586-020-2904-6","article-title":"Molecular dissection of amyloid disaggregation by human HSP70","volume":"587","author":"Wentink","year":"2020","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Jawed, A., Ho, C.-T., Grousl, T., Shrivastava, A., Ruppert, T., Bukau, B., and Mogk, A. (2022). Balanced activities of Hsp70 and the ubiquitin proteasome system underlie cellular protein homeostasis. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.1106477"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.3389\/fphar.2019.01047","article-title":"Small Heat Shock Proteins, Big Impact on Protein Aggregation in Neurodegenerative Disease","volume":"10","author":"Webster","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1091\/mbc.e12-03-0194","article-title":"Molecular chaperones and stress-inducible protein-sorting factors coordinate the spatiotemporal distribution of protein aggregates","volume":"23","author":"Malinovska","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"778","DOI":"10.15252\/embj.201489524","article-title":"Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition","volume":"34","author":"Miller","year":"2015","journal-title":"EMBO J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1083\/jcb.201708116","article-title":"A prion-like domain in Hsp42 drives chaperone-facilitated aggregation of misfolded proteins","volume":"217","author":"Grousl","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Reinle, K., Mogk, A., and Bukau, B. (2022). The Diverse Functions of Small Heat Shock Proteins in the Proteostasis Network. J. Mol. Biol., 434.","DOI":"10.1016\/j.jmb.2021.167157"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S0962-8924(00)01852-3","article-title":"Aggresomes, inclusion bodies and protein aggregation","volume":"10","author":"Kopito","year":"2000","journal-title":"Trends Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/nature02998","article-title":"Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death","volume":"431","author":"Arrasate","year":"2004","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"E5703","DOI":"10.1073\/pnas.1618417114","article-title":"Protein homeostasis of a metastable subproteome associated with Alzheimer\u2019s disease","volume":"114","author":"Kundra","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1083\/jcb.201612111","article-title":"Shaping proteostasis at the cellular, tissue, and organismal level","volume":"216","author":"Sala","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.celrep.2014.09.042","article-title":"A Chaperome Subnetwork Safeguards Proteostasis in Aging and Neurodegenerative Disease","volume":"9","author":"Brehme","year":"2014","journal-title":"Cell Rep."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Moura, C.S., Lollo, P.C.B., Neder Morato, P., and Amaya-Farfan, J. (2018). Dietary Nutrients and Bioactive Substances Modulate Heat Shock Protein (HSP) Expression: A Review. Nutrients, 10.","DOI":"10.3390\/nu10060683"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6676444","DOI":"10.1155\/2021\/6676444","article-title":"The Role of Polyphenols in Regulation of Heat Shock Proteins and Gut Microbiota in Weaning Stress","volume":"2021","author":"Hussain","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s12192-011-0280-8","article-title":"High-dose green tea polyphenols induce nephrotoxicity in dextran sulfate sodium-induced colitis mice by down-regulation of antioxidant enzymes and heat-shock protein expressions","volume":"16","author":"Inoue","year":"2011","journal-title":"Cell Stress Chaperon"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.fct.2014.02.012","article-title":"Quercetin mitigates lead acetate-induced behavioral and histological alterations via suppression of oxidative stress, Hsp-70, Bak and upregulation of Bcl-2","volume":"68","author":"Chander","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"317S","DOI":"10.1093\/ajcn\/81.1.317S","article-title":"Polyphenols and disease risk in epidemiologic studies","volume":"81","author":"Arts","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"806470","DOI":"10.3389\/fphar.2022.806470","article-title":"Dietary Polyphenols and Their Role in Oxidative Stress-Induced Human Diseases: Insights Into Protective Effects, Antioxidant Potentials and Mechanism(s) of Action","volume":"13","author":"Rudrapal","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1089\/ars.2021.0183","article-title":"Cisplatin Chemotherapy and Cochlear Damage: Otoprotective and Chemosensitization Properties of Polyphenols","volume":"36","author":"Fetoni","year":"2022","journal-title":"Antioxid. Redox Signal."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Pisani, A., Paciello, F., Montuoro, R., Rolesi, R., Galli, J., and Fetoni, A.R. (2023). Antioxidant Therapy as an Effective Strategy against Noise-Induced Hearing Loss: From Experimental Models to Clinic. Life, 13.","DOI":"10.3390\/life13041035"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Di Lorenzo, C., Colombo, F., Biella, S., Stockley, C., and Restani, P. (2021). Polyphenols and Human Health: The Role of Bioavailability. Nutrients, 13.","DOI":"10.3390\/nu13010273"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Stromsnes, K., Lagzdina, R., Olaso-Gonzalez, G., Gimeno-Mallench, L., and Gambini, J. (2021). Pharmacological Properties of Polyphenols: Bioavailability, Mechanisms of Action, and Biological Effects in In Vitro Studies, Animal Models, and Humans. Biomedicines, 9.","DOI":"10.3390\/biomedicines9081074"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1080\/09168451.2018.1444467","article-title":"Flavonoid metabolism: The interaction of metabolites and gut microbiota","volume":"82","author":"Murota","year":"2018","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1080\/10408398.2018.1546669","article-title":"Bioactivity of dietary polyphenols: The role of metabolites","volume":"60","author":"Luca","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Ozdal, T., Sela, D.A., Xiao, J., Boyacioglu, D., Chen, F., and Capanoglu, E. (2016). The Reciprocal Interactions between Polyphenols and Gut Microbiota and Effects on Bioaccessibility. Nutrients, 8.","DOI":"10.3390\/nu8020078"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4781","DOI":"10.1021\/pr300581s","article-title":"Metabolomics View on Gut Microbiome Modulation by Polyphenol-rich Foods","volume":"11","author":"Moco","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.jnutbio.2013.05.001","article-title":"Benefits of polyphenols on gut microbiota and implications in human health","volume":"24","author":"Cardona","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"154979","DOI":"10.1016\/j.phymed.2023.154979","article-title":"Interactions between gut microbiota and polyphenols: A mechanistic and metabolomic review","volume":"119","author":"Cheng","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1021\/jf803059z","article-title":"Procyanidin Dimers Are Metabolized by Human Microbiota with 2-(3,4-Dihydroxyphenyl)acetic Acid and 5-(3,4-Dihydroxyphenyl)-\u03b3-valerolactone as the Major Metabolites","volume":"57","author":"Appeldoorn","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1080\/10408398.2020.1744512","article-title":"Dietary polyphenol impact on gut health and microbiota","volume":"61","author":"Wan","year":"2021","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"8908","DOI":"10.1021\/acsomega.0c06156","article-title":"Analysis of Conformational, Structural, Magnetic, and Electronic Properties Related to Antioxidant Activity: Revisiting Flavan, Anthocyanidin, Flavanone, Flavonol, Isoflavone, Flavone, and Flavan-3-ol","volume":"6","author":"Farias","year":"2021","journal-title":"ACS Omega"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1104\/pp.17.00842","article-title":"Flavan-3-ols Are an Effective Chemical Defense against Rust Infection","volume":"175","author":"Ullah","year":"2017","journal-title":"Plant Physiol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Cheng, C.-Y., Barro, L., Tsai, S.-T., Feng, T.-W., Wu, X.-Y., Chao, C.-W., Yu, R.-S., Chin, T.-Y., and Hsieh, M.F. (2021). Epigallocatechin-3-Gallate-Loaded Liposomes Favor Anti-Inflammation of Microglia Cells and Promote Neuroprotection. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063037"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.1111\/ejn.12362","article-title":"Oral administration of the flavanol (\u2212)-epicatechin bolsters endogenous protection against focal ischemia through the Nrf2 cytoprotective pathway","volume":"38","author":"Leonardo","year":"2013","journal-title":"Eur. J. Neurosci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1038\/jcbfm.2010.53","article-title":"The flavanol (-)-epicatechin prevents stroke damage through the Nrf2\/HO1 pathway","volume":"30","author":"Shah","year":"2010","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ejphar.2015.11.048","article-title":"Epigallocatechin gallate attenuates amyloid \u03b2-induced inflammation and neurotoxicity in EOC 13.31 microglia","volume":"770","author":"Wei","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"5931","DOI":"10.1096\/fj.201903125RR","article-title":"EGCG ameliorates neuronal and behavioral defects by remodeling gut microbiota and TotM expression in Drosophila models of Parkinson\u2019s disease","volume":"34","author":"Xu","year":"2020","journal-title":"FASEB J."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Kim, S.-J., Lee, J.-H., Kim, B.-S., So, H.-S., Park, R., Myung, N.-Y., Um, J.-Y., and Hong, S.-H. (2012). (-)-Epigallocatechin-3-Gallate Protects against NO-Induced Ototoxicity through the Regulation of Caspase- 1, Caspase-3, and NF-\u03baB Activation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043967"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1007\/s11064-015-1584-3","article-title":"Green Tea Polyphenols Protects Cochlear Hair Cells from Ototoxicity by Inhibiting Notch Signalling","volume":"40","author":"Gu","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.exger.2016.07.005","article-title":"Protective effect of polyphenols on presbycusis via oxidative\/nitrosative stress suppression in rats","volume":"83","author":"Cuadrado","year":"2016","journal-title":"Exp. Gerontol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Rivas-Chac\u00f3n, L.d.M., Yanes-D\u00edaz, J., de Lucas, B., Riestra-Ayora, J.I., Madrid-Garc\u00eda, R., Sanz-Fern\u00e1ndez, R., and S\u00e1nchez-Rodr\u00edguez, C. (2022). Preventive Effect of Cocoa Flavonoids via Suppression of Oxidative Stress-Induced Apoptosis in Auditory Senescent Cells. Antioxidants, 11.","DOI":"10.3390\/antiox11081450"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.ypmed.2004.10.014","article-title":"Antioxidative properties of black tea","volume":"40","author":"Skrzydlewska","year":"2005","journal-title":"Prev. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1093\/nutrit\/nux070","article-title":"Possible mechanisms of postprandial physiological alterations following flavan 3-ol ingestion","volume":"76","author":"Osakabe","year":"2018","journal-title":"Nutr. Rev."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S0891-5849(02)00871-7","article-title":"Absorption and urinary excretion of procyanidin b2 [epicatechin-(4beta-8)-epicatechin] in rats","volume":"33","author":"Baba","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1017\/S0007114509992741","article-title":"Bioavailability of procyanidin dimers and trimers and matrix food effects in in vitro and in vivo models","volume":"103","author":"Serra","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Al-Khayri, J.M., Mascarenhas, R., Harish, H.M., Gowda, Y., Lakshmaiah, V.V., Nagella, P., Al-Mssallem, M.Q., Alessa, F.M., Almaghasla, M.I., and Rezk, A.A.-S. (2023). Stilbenes, a Versatile Class of Natural Metabolites for Inflammation\u2014An Overview. Molecules, 28.","DOI":"10.3390\/molecules28093786"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"591836","DOI":"10.3389\/fphar.2020.591836","article-title":"Protective Effects of Pterostilbene on Lipopolysaccharide-Induced Acute Lung Injury in Mice by Inhibiting NF-\u03baB and Activating Nrf2\/HO-1 Signaling Pathways","volume":"11","author":"Zhang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"877098","DOI":"10.3389\/fphar.2022.877098","article-title":"SIRT1 Is Involved in the Neuroprotection of Pterostilbene Against Amyloid \u03b2 25\u201335-Induced Cognitive Deficits in Mice","volume":"13","author":"Zhu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ijporl.2014.11.008","article-title":"Protective effect of resveratrol against cisplatin-induced ototoxicity in HEI-OC1 auditory cells","volume":"79","author":"Lee","year":"2015","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4149\/BLL_2023_033","article-title":"Epigallocatechin-3-gallate and resveratrol attenuate hydrogen peroxide induced damage in neuronal cells","volume":"124","author":"Cosar","year":"2023","journal-title":"Bratisl. Med. J."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Wang, P., Du, B., Yin, W., Wang, X., and Zhu, W. (2013). Resveratrol Attenuates CoCl2-Induced Cochlear Hair Cell Damage through Upregulation of Sirtuin1 and NF-\u03baB Deacetylation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080854"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Lee, C.H., Kim, K.W., Lee, S.M., and Kim, S.Y. (2020). Dose-Dependent Effects of Resveratrol on Cisplatin-Induced Hearing Loss. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010113"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"910308","DOI":"10.3389\/fphar.2022.910308","article-title":"Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing Loss","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"290","DOI":"10.5152\/iao.2016.2617","article-title":"A Prospective Experimental Study on the Protective Effect of Resveratrol against Amikacin-Induced Ototoxicity in Rats","volume":"12","author":"Avci","year":"2016","journal-title":"J. Int. Adv. Otol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1007\/s00405-019-05635-x","article-title":"Comparison of the protective efficacy between intratympanic dexamethasone and resveratrol treatments against cisplatin-induced ototoxicity: An experimental study","volume":"276","author":"Simsek","year":"2019","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.neurobiolaging.2019.04.003","article-title":"SIRT1 protects cochlear hair cell and delays age-related hearing loss via autophagy","volume":"80","author":"Pang","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1139\/bcb-2020-0459","article-title":"Resveratrol upregulates miR-455-5p to antagonize cisplatin ototoxicity via modulating the PTEN\u2013PI3K\u2013AKT axis","volume":"99","author":"Liu","year":"2021","journal-title":"Biochem. Cell Biol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.neurobiolaging.2019.03.013","article-title":"Modulation of miR-34a\/SIRT1 signaling protects cochlear hair cells against oxidative stress and delays age-related hearing loss through coordinated regulation of mitophagy and mitochondrial biogenesis","volume":"79","author":"Xiong","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1159\/000485312","article-title":"Resveratrol Promotes Recovery of Hearing following Intense Noise Exposure by Enhancing Cochlear SIRT1 Activity","volume":"22","author":"Xiong","year":"2017","journal-title":"Audiol. Neurotol."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Springer, M., and Moco, S. (2019). Resveratrol and Its Human Metabolites\u2014Effects on Metabolic Health and Obesity. Nutrients, 11.","DOI":"10.3390\/nu11010143"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1124\/dmd.104.000885","article-title":"High absorption but very low bioavailability of oral resveratrol in humans","volume":"32","author":"Walle","year":"2004","journal-title":"Drug Metab. Dispos."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"5957","DOI":"10.1007\/s00253-019-09914-9","article-title":"Chemical, physical and biotechnological approaches to the production of the potent antioxidant hydroxytyrosol","volume":"103","author":"Britton","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_142","first-page":"1492","article-title":"Pharmacokinetics and metabolism of hydroxytyrosol, a natural antioxidant from olive oil","volume":"29","author":"Manna","year":"2001","journal-title":"Drug Metab. Dispos."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Nikou, T., Sakavitsi, M.E., Kalampokis, E., and Halabalaki, M. (2022). Metabolism and Bioavailability of Olive Bioactive Constituents Based on In Vitro, In Vivo and Human Studies. Nutrients, 14.","DOI":"10.3390\/nu14183773"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.fct.2006.01.008","article-title":"Safety assessment of aqueous olive pulp extract as an antioxidant or antimicrobial agent in foods","volume":"44","author":"Soni","year":"2006","journal-title":"Food Chem. Toxicol."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Luo, S., Jiang, X., Jia, L., Tan, C., Li, M., Yang, Q., Du, Y., and Ding, C. (2019). In Vivo and In Vitro Antioxidant Activities of Methanol Extracts from Olive Leaves on Caenorhabditis elegans. Molecules, 24.","DOI":"10.3390\/molecules24040704"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jnutbio.2015.09.026","article-title":"Extra virgin olive oil rich in polyphenols modulates VEGF-induced angiogenic responses by preventing NADPH oxidase activity and expression","volume":"28","author":"Calabriso","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00210-009-0399-7","article-title":"Hydroxytyrosol inhibits pro-inflammatory cytokines, iNOS, and COX-2 expression in human monocytic cells","volume":"379","author":"Zhang","year":"2009","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/bcp.12993","article-title":"Oleuropein aglycone and polyphenols from olive mill waste water ameliorate cognitive deficits and neuropathology","volume":"83","author":"Pantano","year":"2017","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"4070935","DOI":"10.1155\/2018\/4070935","article-title":"Effects of Long-Term Treatment with a Blend of Highly Purified Olive Secoiridoids on Cognition and Brain ATP Levels in Aged NMRI Mice","volume":"2018","author":"Reutzel","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"173338","DOI":"10.1016\/j.ejphar.2020.173338","article-title":"Hydroxytyrosol enhances cisplatin-induced ototoxicity: Possible relation to the alteration in the activity of JNK and AIF pathways","volume":"887","author":"Zhang","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1021\/acs.jmedchem.6b00975","article-title":"The essential medicinal chemistry of curcumin","volume":"60","author":"Nelson","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"5747","DOI":"10.1002\/jsfa.11372","article-title":"Curcumin, the active substance of turmeric: Its effects on health and ways to improve its bioavailability","volume":"101","author":"Swelum","year":"2021","journal-title":"J. Sci. Food Agric."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3390\/molecules20010185","article-title":"Curcumin Differs from Tetrahydrocurcumin for Molecular Targets, Signaling Pathways and Cellular Responses","volume":"20","author":"Aggarwal","year":"2014","journal-title":"Molecules"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2019.02.020","article-title":"Antioxidant effects of curcumin in models of neurodegeneration, aging, oxidative and nitrosative stress: A review","volume":"406","author":"Abrahams","year":"2019","journal-title":"Neuroscience"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1007\/s11011-017-0093-2","article-title":"Curcumin revitalizes Amyloid beta (25\u201335)-induced and organophosphate pesticides pestered neurotoxicity in SH-SY5Y and IMR-32 cells via activation of APE1 and Nrf2","volume":"32","author":"Sarkar","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ijporl.2016.08.012","article-title":"Intraperitoneal curcumin and vitamin E combination for the treatment of cisplatin-induced ototoxicity in rats","volume":"89","author":"Gevrek","year":"2016","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e169","DOI":"10.1097\/MAO.0000000000000302","article-title":"Curcuma Longa (Curcumin) Decreases In Vivo Cisplatin-Induced Ototoxicity through Heme Oxygenase-1 Induction","volume":"35","author":"Fetoni","year":"2014","journal-title":"Otol. Neurotol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Dei Cas, M., and Ghidoni, R. (2019). Dietary Curcumin: Correlation between Bioavailability and Health Potential. Nutrients, 11.","DOI":"10.3390\/nu11092147"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"803657","DOI":"10.3389\/fvets.2021.803657","article-title":"Biological Function of Plant Tannin and Its Application in Animal Health","volume":"8","author":"Tong","year":"2021","journal-title":"Front. Veter-Sci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.indcrop.2012.02.038","article-title":"Characterization of pomegranate peels tannin extractives","volume":"40","author":"Saad","year":"2012","journal-title":"Ind. Crop. Prod."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ijporl.2016.01.014","article-title":"Protective effects of the seaweed phlorotannin polyphenolic compound dieckol on gentamicin-induced damage in auditory hair cells","volume":"83","author":"Chang","year":"2016","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Fraga-Corral, M., Otero, P., Cassani, L., Echave, J., Garcia-Oliveira, P., Carpena, M., Chamorro, F., Louren\u00e7o-Lopes, C., Prieto, M.A., and Simal-Gandara, J. (2021). Traditional Applications of Tannin Rich Extracts Supported by Scientific Data: Chemical Composition, Bioavailability and Bioaccessibility. Foods, 10.","DOI":"10.3390\/foods10020251"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Fabbrini, M., D\u2019amico, F., Barone, M., Conti, G., Mengoli, M., Brigidi, P., and Turroni, S. (2022). Polyphenol and Tannin Nutraceuticals and Their Metabolites: How the Human Gut Microbiota Influences Their Properties. Biomolecules, 12.","DOI":"10.3390\/biom12070875"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0031-9422(02)00513-7","article-title":"Rosmarinic acid","volume":"62","author":"Petersen","year":"2003","journal-title":"Phytochemistry"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1111\/j.1365-2222.2004.01979.x","article-title":"Rosmarinic acid in perilla extract inhibits allergic inflammation induced by mite allergen, in a mouse model","volume":"34","author":"Sanbongi","year":"2004","journal-title":"Clin. Exp. Allergy"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/S0891-5849(03)00040-6","article-title":"Rosmarinic acid inhibits lung injury induced by diesel exhaust particles","volume":"34","author":"Sanbongi","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/S0891-5849(02)00970-X","article-title":"Rosmarinic acid, a major polyphenolic component of perilla frutescens, reduces lipopolysaccharide (lps)-induced liver injury in d-galactosamine (d-galn)-sensitized mice","volume":"33","author":"Osakabe","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/carcin\/bgh034","article-title":"Rosmarinic acid inhibits epidermal inflammatory responses: Anticarcinogenic effect of Perilla frutescens extract in the murine two-stage skin model","volume":"25","author":"Osakabe","year":"2004","journal-title":"Carcinogenesis"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/biof.552210125","article-title":"Anti-inflammatory and anti-allergic effect of rosmarinic acid (RA); inhibition of seasonal allergic rhinoconjunctivitis (SAR) and its mechanism","volume":"21","author":"Osakabe","year":"2004","journal-title":"BioFactors"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1177\/153537020422900305","article-title":"Extract of perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans","volume":"229","author":"Takano","year":"2004","journal-title":"Exp. Biol. Med."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1142\/S0192415X13500298","article-title":"Protective effect of rosmarinic acid is through regulation of inflammatory cytokine in cadmium-induced ototoxicity","volume":"41","author":"Kim","year":"2013","journal-title":"Am. J. Chin. Med."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Jeong, H.-J., Choi, Y., Kim, M.-H., Kang, I.-C., Lee, J.-H., Park, C., Park, R., and Kim, H.-M. (2011). Rosmarinic Acid, Active Component of Dansam-Eum Attenuates Ototoxicity of Cochlear Hair Cells through Blockage of Caspase-1 Activity. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018815"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1097\/MAO.0000000000001700","article-title":"The Antioxidant Effect of Rosmarinic Acid by Different Delivery Routes in the Animal Model of Noise-Induced Hearing Loss","volume":"39","author":"Fetoni","year":"2018","journal-title":"Otol. Neurotol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.freeradbiomed.2015.04.021","article-title":"Rosmarinic acid up-regulates the noise-activated Nrf2\/HO-1 pathway and protects against noise-induced injury in rat cochlea","volume":"85","author":"Fetoni","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00394-004-0482-2","article-title":"Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans","volume":"44","author":"Baba","year":"2005","journal-title":"Eur. J. Nutr."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.amjoto.2012.07.003","article-title":"The protective role of caffeic acid phenethyl ester against streptomycin ototoxicity","volume":"34","author":"Abakay","year":"2013","journal-title":"Am. J. Otolaryngol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1016\/j.ijporl.2014.10.013","article-title":"Effects of caffeic acid on cisplatin-induced hair cell damage in HEI-OC1 auditory cells","volume":"78","author":"Choi","year":"2014","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.ijporl.2014.05.018","article-title":"Protective effects of caffeic acid phenethyl ester (CAPE) against neomycin-induced hair cell damage in zebrafish","volume":"78","author":"Park","year":"2014","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ijporl.2019.02.001","article-title":"The protective role of ferulic acid against cisplatin-induced ototoxicity","volume":"120","author":"Jo","year":"2019","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1016\/j.neuroscience.2010.06.022","article-title":"In vivo protective effect of ferulic acid against noise-induced hearing loss in the guinea-pig","volume":"169","author":"Fetoni","year":"2010","journal-title":"Neuroscience"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3109\/00016489.2010.539263","article-title":"Therapeutic window for ferulic acid protection against noise-induced hearing loss in the guinea pig","volume":"131","author":"Fetoni","year":"2011","journal-title":"Acta Oto-Laryngol."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Rassu, G., Sorrenti, M., Catenacci, L., Pavan, B., Ferraro, L., Gavini, E., Bonferoni, M.C., Giunchedi, P., and Dalpiaz, A. (2023). Conjugation, Prodrug, and Co-Administration Strategies in Support of Nanotechnologies to Improve the Therapeutic Efficacy of Phytochemicals in the Central Nervous System. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061578"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2022.04.003","article-title":"Enhancement of blood\u2013brain barrier penetration and the neuroprotective effect of resveratrol","volume":"346","author":"Katila","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"46406","DOI":"10.1021\/acsami.1c14818","article-title":"Oral Administration of Resveratrol-Selenium-Peptide Nanocomposites Alleviates Alzheimer\u2019s Disease-like Pathogenesis by Inhibiting A\u03b2 Aggregation and Regulating Gut Microbiota","volume":"13","author":"Li","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.colsurfb.2014.03.054","article-title":"Resveratrol-loaded nanocarriers: Formulation, optimization, characterization and in vitro toxicity on cochlear cells","volume":"118","author":"Musazzi","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1097\/MAO.0000000000000403","article-title":"Attenuation of Cisplatin Ototoxicity by Otoprotective Effects of Nanoencapsulated Curcumin and Dexamethasone in a Guinea Pig Model","volume":"35","author":"Salehi","year":"2014","journal-title":"Otol. Neurotol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1021\/acs.molpharmaceut.2c00067","article-title":"Curcumin-Encapsulated Chitosan-Coated Nanoformulation as an Improved Otoprotective Strategy for Ototoxic Hearing Loss","volume":"19","author":"Chen","year":"2022","journal-title":"Mol. Pharm."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jphs.2017.07.003","article-title":"Preventive effect of curcumin and its highly bioavailable preparation on hearing loss induced by single or repeated exposure to noise: A comparative and mechanistic study","volume":"134","author":"Yamaguchi","year":"2017","journal-title":"J. Pharmacol. Sci."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1093\/hmg\/9.6.869","article-title":"A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes","volume":"9","author":"Culetto","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/35888","article-title":"Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans","volume":"391","author":"Fire","year":"1998","journal-title":"Nature"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"681","DOI":"10.3233\/JAD-2010-1267","article-title":"Behavioral Phenotyping of a Transgenic Caenorhabditis Elegans Expressing Neuronal Amyloid-\u03b2","volume":"19","author":"Dosanjh","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.nbd.2017.10.003","article-title":"Human amyloid \u03b2 peptide and tau co-expression impairs behavior and causes specific gene expression changes in Caenorhabditis elegans","volume":"109","author":"Wang","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Huang, X., Wang, C., Chen, L., Zhang, T., Leung, K.L., and Wong, G. (2021). Human amyloid beta and \u03b1-synuclein co-expression in neurons impair behavior and recapitulate features for Lewy body dementia in Caenorhabditis elegans. Biochim. Biophys. Acta (BBA)-Mol. Basis Dis., 1867.","DOI":"10.1016\/j.bbadis.2021.166203"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1073\/pnas.042497999","article-title":"Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans","volume":"99","author":"Nass","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1074\/jbc.M505581200","article-title":"Conversion of Green Fluorescent Protein into a Toxic, Aggregation-prone Protein by C-terminal Addition of a Short Peptide","volume":"281","author":"Link","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Wang, J., Farr, G.W., Hall, D.H., Li, F., Furtak, K., Dreier, L., and Horwich, A.L. (2009). An ALS-Linked Mutant SOD1 Produces a Locomotor Defect Associated with Aggregation and Synaptic Dysfunction When Expressed in Neurons of Caenorhabditis elegans. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000350"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"E277","DOI":"10.1073\/pnas.1412192112","article-title":"Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants","volume":"112","author":"Bansal","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1021\/acschemneuro.1c00548","article-title":"Anti-\u03b1-synuclein Toxicity and Anti-neurodegenerative Role of Chrysin in Transgenic Caenorhabditis elegans Models of Parkinson\u2019s Disease","volume":"13","author":"Muhammad","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"984","DOI":"10.2174\/1871527311211080007","article-title":"Iridoid Compound 10-O-trans-p-Coumaroylcatalpol Extends Longevity and Reduces Alpha Synuclein Aggregation in Caenorhabditis elegans","volume":"11","author":"Shukla","year":"2012","journal-title":"CNS Neurol. Disord.-Drug Targets"},{"key":"ref_200","first-page":"524878","article-title":"Catalpol Modulates Lifespan via DAF-16\/FOXO and SKN-1\/Nrf2 Activation inCaenorhabditis elegans. Evidence-Based Complement","volume":"2015","author":"Seo","year":"2015","journal-title":"Altern. Med."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1002\/mnfr.201400014","article-title":"Amyloid-beta (A\u03b21\u201342)-induced paralysis inCaenorhabditis elegansis inhibited by the polyphenol quercetin through activation of protein degradation pathways","volume":"58","author":"Regitz","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"287","DOI":"10.3233\/JAD-2003-5404","article-title":"Elevation of oxidative free radicals in Alzheimer\u2019s disease models can be attenuated by Ginkgo biloba extract EGb 761","volume":"5","author":"Smith","year":"2003","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Diomede, L., Rigacci, S., Romeo, M., Stefani, M., and Salmona, M. (2013). Oleuropein Aglycone Protects Transgenic C. elegans Strains Expressing A\u03b242 by Reducing Plaque Load and Motor Deficit. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058893"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1038\/nprot.2012.115","article-title":"Generation of human induced pluripotent stem cells from urine samples","volume":"7","author":"Zhou","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"768391","DOI":"10.1155\/2014\/768391","article-title":"A Comparative View on Human Somatic Cell Sources for iPSC Generation","volume":"2014","author":"Raab","year":"2014","journal-title":"Stem Cells Int."},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Torrens-Mas, M., Perell\u00f3-Reus, C., Navas-Enamorado, C., Ibarg\u00fcen-Gonz\u00e1lez, L., Sanchez-Polo, A., Segura-Sampedro, J.J., Masmiquel, L., Barcelo, C., and Gonzalez-Freire, M. (2021). Organoids: An Emerging Tool to Study Aging Signature across Human Tissues. Modeling Aging with Patient-Derived Organoids. Int. J. Mol. Sci., 22.","DOI":"10.20944\/preprints202109.0182.v1"},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Gulimiheranmu, M., Li, S., and Zhou, J. (2021). In Vitro Recapitulation of Neuropsychiatric Disorders with Pluripotent Stem Cells-Derived Brain Organoids. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph182312431"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"77001","DOI":"10.1289\/EHP8580","article-title":"Gene\u2013Environment Interactions in Developmental Neurotoxicity: A Case Study of Synergy between Chlorpyrifos and CHD8 Knockout in Human BrainSpheres","volume":"129","author":"Modafferi","year":"2021","journal-title":"Environ. Health Perspect."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1007\/s11064-017-2289-6","article-title":"Genipin Inhibits LPS-Induced Inflammatory Response in BV2 Microglial Cells","volume":"42","author":"Wang","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_210","first-page":"639862","article-title":"Selective Th2 Upregulation byCrocus sativus: A Neutraceutical Spice. Evidence-Based Complement","volume":"2011","author":"Bani","year":"2010","journal-title":"Altern. Med."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1742-4933-10-41","article-title":"Cellular stress response, sirtuins and UCP proteins in Alzheimer disease: Role of vitagenes","volume":"10","author":"Cornelius","year":"2013","journal-title":"Immun. Ageing"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12979-017-0108-1","article-title":"Neuroinflammation and neurohormesis in the pathogenesis of Alzheimer\u2019s disease and Alzheimer-linked pathologies: Modulation by nutritional mushrooms","volume":"15","author":"Salinaro","year":"2018","journal-title":"Immun. Ageing"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1002\/jnr.23986","article-title":"Inflammasomes, hormesis, and antioxidants in neuroinflammation: Role of NRLP3 in Alzheimer disease","volume":"95","author":"Pennisi","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0014-5793(96)00647-3","article-title":"Nuclear DNA strand breaks during ethanol-induced oxidative stress in rat brain","volume":"390","author":"Renis","year":"1996","journal-title":"FEBS Lett."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"102074","DOI":"10.1016\/j.arr.2023.102074","article-title":"Hormesis defines the limits of lifespan","volume":"91","author":"Calabrese","year":"2023","journal-title":"Ageing Res. Rev."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/11\/2045\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:26:27Z","timestamp":1760131587000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/11\/2045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,20]]},"references-count":215,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["medicina59112045"],"URL":"https:\/\/doi.org\/10.3390\/medicina59112045","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,20]]}}}