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Herein, we proposed a multimodal AI\u2010driven Traditional Chinese Medicine (TCM) symptom prediction model (TCM\u2010SPred) and predicted potential herb\u2010symptom associations between herbs and symptoms to obtain agents for treating renal fibrosis. The prediction results of TCM\u2010SPred revealed that a natural guaianolide sesquiterpene lactone derivative dehydrocostus lactone (DCL, a main chemical constituent of Aucklandiae Radix) demonstrated significant anti\u2010fibrotic effects in vivo (unilateral ureteral obstruction) and in vitro (TGF\u2010\u03b21\u2010induced epithelial\u2010mesenchymal transition). DCL directly targeted IQGAP1 to inhibit the Wnt signaling pathway by blocking the interaction between IQGAP1 and CCT3. These findings highlight the potential of DCL as a promising therapeutic candidate for renal fibrosis, providing novel insights into the IQGAP1\u2010CCT3\u2010Wnt signaling axis as a potential target for renal fibrosis intervention.<\/jats:p>","DOI":"10.1002\/advs.202520277","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T15:25:05Z","timestamp":1770132305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multimodal AI\u2010Driven Identification of Dehydrocostus Lactone as a Potent Renal Fibrosis Attenuator Targeting IQGAP1"],"prefix":"10.1002","volume":"13","author":[{"given":"Weijiang","family":"Lin","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Functional Substance of Chinese Medicine School of Pharmacy Nanjing University of Chinese Medicine  Nanjing P. R. 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