GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328003/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328003GEOGSEfalseHonokiol-mediated reversal of cisplatin-induced transcriptomic changes in outer hair cellsCisplatin-induced hearing loss (CIHL) affects half a million cancer patients annually, but treatment strategies are limited. We have previously shown that honokiol upregulates mitochondrial sirtuin 3 (SIRT3) and protects against CIHL. In the present study, we further investigated the mechanisms of honokiol and the role of Sirt3 in protection against CIHL by using a Sirt3 knockout (Sirt3−/−) mouse model and by performing RNA-seq on outer hair cells. Our results showed that honokiol ameliorated cisplatin-induced cochlear functional deterioration in both wild-type and Sirt3−/− mice. RNA-seq analysis showed that cisplatin treatment resulted in the downregulation of mitochondrial-related transcriptome and important antioxidant genes, such as isocitrate dehydrogenase 2 (Idh2). Honokiol pre-treatment reversed this pattern by upregulating genes suppressed by cisplatin. These results highlight the clinical potential of honokiol as a protective agent during chemotherapy, while suggesting that Idh2, a substrate of Sirt3, is a promising therapeutic target.2026/08/19GSE328003GSM9670209GSM9670208GSM9670229GSM9670228GSM9670227GSM9670237GSM9670215GSM9670214GSM9670236GSM9670235GSM9670213GSM9670234GSM9670212GSM9670211GSM9670233GSM9670232GSM9670210GSM9670231GSM9670230GSM9670219GSM9670218GSM9670239GSM9670217GSM9670216GSM9670238GSM9670226GSM9670225GSM9670224GSM9670223GSM9670222GSM9670221GSM967022034290328003Mus musculus