{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T02:47:44Z","timestamp":1793587664768,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.<\/jats:p>","DOI":"10.3390\/md19080443","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:51:07Z","timestamp":1627854667000},"page":"443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model"],"prefix":"10.3390","volume":"19","author":[{"given":"Hyunjun","family":"Woo","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6907-3326","authenticated-orcid":false,"given":"Sohyeon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Interdisciplinary Program in Neuroscience, College of Natural Sciences, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Hee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon-Cheol","family":"Shin","sequence":"additional","affiliation":[{"name":"CEWIT Center for Systems Biology, State University of New York, Incheon 21985, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeong-gon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Sensory Organ Research Institute, Medical Research Center, Seoul National University, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Ha","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Sensory Organ Research Institute, Medical Research Center, Seoul National University, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung-Whan","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Sensory Organ Research Institute, Medical Research Center, Seoul National University, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8635-797X","authenticated-orcid":false,"given":"Moo-Kyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Sensory Organ Research Institute, Medical Research Center, Seoul National University, Seoul 03080, Korea"},{"name":"Wide River Institute of Immunology,  College of Medicine, Seoul National University, Hongcheon 25159, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,1]]},"reference":[{"key":"ref_1","unstructured":"Concha-Barrientos, M., Steenland, K., Pruss-Ustun, A., Campbell-Lendrum, D.H., Corval\u00e1n, C.F., Woodward, A., and WHO (2021, June 20). Occupational Noise: Assessing the Burden of Disease from Work-related Hearing Impairment at National and Local Levels\/Marisol Concha-Barrientos, Diarmid Campbell-Lendrum, Kyle Steenland. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/43001."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.aud.0000191942.36672.f3","article-title":"The role of oxidative stress in noise-induced hearing loss","volume":"27","author":"Henderson","year":"2006","journal-title":"Ear Hear."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00405-012-1979-6","article-title":"Noise-induced hearing threshold shift among US adults and implications for noise-induced hearing loss: National Health and Nutrition Examination Surveys","volume":"270","author":"Mahboubi","year":"2013","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rhee, J., Lee, D., Lim, H.J., Park, M.K., Suh, M.W., Lee, J.H., Hong, Y.C., and Oh, S.H. (2019). Hearing loss in Korean adolescents: The prevalence thereof and its association with leisure noise exposure. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0209254"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1002\/ajim.20223","article-title":"The global burden of occupational noise-induced hearing loss","volume":"48","author":"Nelson","year":"2005","journal-title":"Am. J. Ind. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1523\/JNEUROSCI.4985-05.2006","article-title":"Acceleration of age-related hearing loss by early noise exposure: Evidence of a misspent youth","volume":"26","author":"Kujawa","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-2981-8_1","article-title":"Noise-Induced Hearing Loss: Permanent Versus Temporary Threshold Shifts and the Effects of Hair Cell Versus Neuronal Degeneration","volume":"875","author":"Liberman","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s40463-017-0219-x","article-title":"Current insights in noise-induced hearing loss: A literature review of the underlying mechanism, pathophysiology, asymmetry, and management options","volume":"46","author":"Le","year":"2017","journal-title":"J. Otolaryngol. Head Neck Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.4103\/1463-1741.137057","article-title":"Comparison of the effects of N-acetyl-cysteine and ginseng in prevention of noise induced hearing loss in male textile workers","volume":"16","author":"Doosti","year":"2014","journal-title":"Noise Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1016\/j.bmc.2009.01.031","article-title":"Chemical components and its antioxidant properties in vitro: An edible marine brown alga, Ecklonia cava","volume":"17","author":"Li","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"12073","DOI":"10.1021\/jf802732n","article-title":"Anti-allergic effects of phlorotannins on histamine release via binding inhibition between IgE and Fc epsilonRI","volume":"56","author":"Li","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_12","first-page":"676","article-title":"Identification of chemical structure and free radical scavenging activity of diphlorethohydroxycarmalol isolated from a brown alga, Ishige okamurae","volume":"18","author":"Heo","year":"2008","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s11130-008-0098-4","article-title":"Antidiabetic and antioxidant effects of polyphenols in brown alga Ecklonia stolonifera in genetically diabetic KK-A(y) mice","volume":"63","author":"Iwai","year":"2008","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/BF02976957","article-title":"Antioxidative properties of brown algae polyphenolics and their perspectives as chemopreventive agents against vascular risk factors","volume":"26","author":"Kang","year":"2003","journal-title":"Arch. Pharm. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ijporl.2016.06.028","article-title":"Protective effect of a purified polyphenolic extract from Ecklonia cava against noise-induced hearing loss: Prevention of temporary threshold shift","volume":"87","author":"Chang","year":"2016","journal-title":"Int. J. Pediatric Otorhinolaryngol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Paudel, P., Seong, S.H., Park, S.E., Ryu, J.H., Jung, H.A., and Choi, J.S. (2021). In Vitro and In Silico Characterization of G-Protein Coupled Receptor (GPCR) Targets of Phlorofucofuroeckol-A and Dieckol. Marine Drugs, 19.","DOI":"10.3390\/md19060326"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1172\/JCI116143","article-title":"Formation of novel non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in carbon tetrachloride hepatotoxicity. An animal model of lipid peroxidation","volume":"90","author":"Morrow","year":"1992","journal-title":"J. Clin. Investg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1159\/000071061","article-title":"8-iso-prostaglandin F(2alpha), a product of noise exposure, reduces inner ear blood flow","volume":"8","author":"Miller","year":"2003","journal-title":"Audiol. Neurootol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0006-8993(00)02733-5","article-title":"Intense noise induces formation of vasoactive lipid peroxidation products in the cochlea","volume":"878","author":"Ohinata","year":"2000","journal-title":"Brain Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0304-3940(97)00462-X","article-title":"Efflux of glutamate into the perilymph of the cochlea following transient ischemia in the gerbil","volume":"230","author":"Hakuba","year":"1997","journal-title":"Neurosci. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/(SICI)1096-9861(20000306)418:2<217::AID-CNE7>3.0.CO;2-L","article-title":"Hearing loss and glutamate efflux in the perilymph following transient hindbrain ischemia in gerbils","volume":"418","author":"Hakuba","year":"2000","journal-title":"J. Comp. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1288\/00005537-195906000-00001","article-title":"Experiments on temporary obstruction of the internal auditory artery","volume":"69","author":"Perlman","year":"1959","journal-title":"Laryngoscope"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0378-5955(02)00349-0","article-title":"Outer hair cells functionally and structurally deteriorate during reperfusion","volume":"173","author":"Tabuchi","year":"2002","journal-title":"Hear. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4011","DOI":"10.1523\/JNEUROSCI.2282-12.2013","article-title":"Noise-induced hearing loss (NIHL) as a target of oxidative stress-mediated damage: Cochlear and cortical responses after an increase in antioxidant defense","volume":"33","author":"Fetoni","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3389\/fncel.2020.00226","article-title":"Antioxidants and Vasodilators for the Treatment of Noise-Induced Hearing Loss: Are They Really Effective?","volume":"14","author":"Alvarado","year":"2020","journal-title":"Front. Cell Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3109\/10715762.2013.861599","article-title":"Therapeutic effects of orally administrated antioxidant drugs on acute noise-induced hearing loss","volume":"48","author":"Choi","year":"2014","journal-title":"Free Radic. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107880","DOI":"10.1016\/j.heares.2019.107880","article-title":"Novel oral multifunctional antioxidant prevents noise-induced hearing loss and hair cell loss","volume":"388","author":"Chen","year":"2020","journal-title":"Hear. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/S0378-5955(00)00176-3","article-title":"Reduction of noise-induced hearing loss using L-NAC and salicylate in the chinchilla","volume":"149","author":"Kopke","year":"2000","journal-title":"Hear. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.heares.2012.01.013","article-title":"Antioxidant treatment reduces blast-induced cochlear damage and hearing loss","volume":"285","author":"Ewert","year":"2012","journal-title":"Hear. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1080\/00016480410023038","article-title":"Prevention of impulse noise-induced hearing loss with antioxidants","volume":"125","author":"Kopke","year":"2005","journal-title":"Acta. Otolaryngol."},{"key":"ref_31","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. Pediatric Otorhinolaryngol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1248\/cpb.51.1012","article-title":"A new phlorotannin from the brown alga Ecklonia stolonifera","volume":"51","author":"Kang","year":"2003","journal-title":"Chem. Pharm. Bull."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1007\/BF02980106","article-title":"Inhibitory phlorotannins from the edible brown alga Ecklonia stolonifera on total reactive oxygen species (ROS) generation","volume":"27","author":"Kang","year":"2004","journal-title":"Arch. Pharm. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.1021\/jf900820x","article-title":"Isolation and identification of phlorotannins from Ecklonia stolonifera with antioxidant and anti-inflammatory properties","volume":"57","author":"Kim","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Eo, H.J., Kwon, T.H., Park, G.H., Song, H.M., Lee, S.J., Park, N.H., and Jeong, J.B. (2016). In Vitro Anticancer Activity of Phlorofucofuroeckol A via Upregulation of Activating Transcription Factor 3 against Human Colorectal Cancer Cells. Mar. Drugs, 14.","DOI":"10.3390\/md14040069"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"526","DOI":"10.3109\/10715762.2013.797080","article-title":"Cytoprotective effect of dieckol on human endothelial progenitor cells (hEPCs) from oxidative stress-induced apoptosis","volume":"47","author":"Lee","year":"2013","journal-title":"Free Radic. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.etap.2013.02.013","article-title":"Protective effect of a marine polyphenol, dieckol against carbon tetrachloride-induced acute liver damage in mouse","volume":"35","author":"Kang","year":"2013","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.etap.2013.09.018","article-title":"Protective effect of dieckol isolated from Ecklonia cava against ethanol caused damage in vitro and in zebrafish model","volume":"36","author":"Kang","year":"2013","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.tiv.2009.11.002","article-title":"Protective effects of dieckol isolated from Ecklonia cava against high glucose-induced oxidative stress in human umbilical vein endothelial cells","volume":"24","author":"Lee","year":"2010","journal-title":"Toxicol. Vitr."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Yang, B., Dong, Y., Wang, F., and Zhang, Y. (2020). Nanoformulations to Enhance the Bioavailability and Physiological Functions of Polyphenols. Molecules, 25.","DOI":"10.3390\/molecules25204613"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.biomaterials.2015.04.045","article-title":"Blood-brain barrier-permeable fluorone-labeled dieckols acting as neuronal ER stress signaling inhibitors","volume":"61","author":"Kwak","year":"2015","journal-title":"Biomaterials"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/19\/8\/443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:38:46Z","timestamp":1760164726000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/19\/8\/443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,1]]},"references-count":41,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["md19080443"],"URL":"https:\/\/doi.org\/10.3390\/md19080443","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,1]]}}}