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Its main side effect - ototoxicity - may impact the quality of patient\u2019s life. Eleutheroside E (EE), the main active component of\n                    <jats:italic>Acanthopanax<\/jats:italic>\n                    , exhibits antioxidant and anti-inflammatory properties. This study investigates the protective effects of EE against cisplatin-induced ototoxicity and its underlying mechanisms. We use\n                    <jats:italic>C57BL\/6\u2009J<\/jats:italic>\n                    mice, the House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, and cultured cochlear basement membranes in our experiments. We employ network pharmacology and 4D-FastDIA quantitative proteomic analysis. Our results demonstrate that Cisplatin significantly impairs auditory function in mice. However, EE co-treatment preserves auditory function across most measured frequencies, correlating with reduced damage to cochlear hair cells and spiral ganglion neurons(SGNs). Here, we show that EE attenuates cisplatin-induced pro-inflammatory responses and cellular pyroptosis, possibly via downregulation of the MAPK\/NF-\u03baB\/NLRP3 signaling pathway. In conclusion, EE may offer a promising strategy for reducing Cisplatin\u2019s ototoxicity without affecting its antitumor efficacy.\n                  <\/jats:p>","DOI":"10.1038\/s42003-025-09490-x","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T11:54:02Z","timestamp":1767873242000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Eleutheroside E alleviates cisplatin-induced ototoxicity by down-regulating MAPK\/NF-\u03baB\/NLRP3 signaling pathway and inhibiting cochlear cell pyroptosis"],"prefix":"10.1038","volume":"9","author":[{"given":"Ya\u2019nan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Busheng","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunjian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihui","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1715-8421","authenticated-orcid":false,"given":"Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8437-1583","authenticated-orcid":false,"given":"Maoli","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6387-953X","authenticated-orcid":false,"given":"Yong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"9490_CR1","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.canlet.2021.07.037","volume":"519","author":"MA Skowron","year":"2021","unstructured":"Skowron, M. 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