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Yi\u2010Shen\u2010Qu\u2010Yu prescription (YSQYP), a traditional Chinese herbal formula, has demonstrated clinical efficacy in the treatment of DKD; however, its bioactive constituents and underlying mechanisms remain poorly defined. This study proposes a structure\u2010based and deep learning\u2013guided screening strategy to identify active compounds within YSQYP that target the vitamin D receptor (VDR). An integrated screening strategy was established, combining virtual screening using conventional docking methods and deep learning tools (CarsiDock and RTMScore), as well as biophysical validation through surface plasmon resonance (SPR). Subsequently, the protective effects of candidate compounds against high\u2010glucose\u2010induced podocyte injury were further validated using biological assays. Among the screened constituents, isorhamnetin, hederagenin, and (+)\u2010catechin exhibited the strongest binding affinities for VDR. Functional assays confirmed their capacity to mitigate high\u2010glucose\u2010induced cytotoxicity and apoptosis in podocytes, with isorhamnetin showing the most potent protective effect. Collectively, this study establishes an efficient strategy for natural product screening and identifies promising VDR\u2010targeting compounds from YSQYP, providing novel therapeutic candidates for the treatment of DKD.<\/jats:p>","DOI":"10.1111\/cbdd.70289","type":"journal-article","created":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T21:19:18Z","timestamp":1775337558000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An\n                    <scp>AI<\/scp>\n                    \u2010Guided Structure\u2010Based Strategy for the Discovery and Biological Validation of Natural Products Targeting the Vitamin D Receptor From\n                    <scp>YSQYP<\/scp>\n                    in Diabetic Kidney 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