Integrating UHPLC-QE-MS and Bioinformatics with Experimental Validation Reveals MAPK/FOS-Mediated Podocyte Apoptosis as the Key Mechanism of Alpiniae oxyphyllae and Saposhnikovia divaricata in Treating Diabetic Kidney Disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41155564", "kind": "science-record", "revision": 3, "content_hash": "sha256:b185c31f5b75084364df2a5f1f28fb8e0eaeb961378a76f447de19a29e97b1c7", "created_at": "2026-11-01T20:31:12Z", "updated_at": "2026-11-01T22:14:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrating UHPLC-QE-MS and Bioinformatics with Experimental Validation Reveals MAPK/FOS-Mediated Podocyte Apoptosis as the Key Mechanism of Alpiniae oxyphyllae and Saposhnikovia divaricata in Treating Diabetic Kidney Disease.", "doi": "10.3390/ph18101449", "pmid": "41155564", "authors": ["Xian Wang", "Lin Zhang", "Rongxin Tang", "Wenlong Zhang", "Yiqiang Xie", "Kai Li"], "journal": "Pharmaceuticals (Basel, Switzerland)", "year": 2025, "abstract": "Background: Alpiniae oxyphyllae-Saposhnikovia divaricata (AS), a traditional Chinese dietary supplement, exhibits potential therapeutic effects against diabetic kidney disease (DKD), though its active compounds and mechanisms require elucidation. Methods: Animal experiments integrated with UHPLC-QE-MS, bioinformatics, and experimental validation were employed to investigate AS's pharmacodynamic basis against DKD. Results: Thirty-nine compounds were identified in AS, including four key flavonoids (daidzein, kaempferol, tectoridin, baicalin). Bioinformatics screening revealed 516 potential AS targets from PubChem/TCMSP/ETCM databases. Analysis of the GEO dataset (GSE30529) identified 482 DKD-related differentially expressed genes (DEGs). Venny 2.1 analysis yielded 42 co-DEGs and 6 co-core DEGs. Functional enrichment (GO/KEGG/GSEA) demonstrated AS's modulation of apoptosis and extracellular matrix (ECM) pathways via these DEGs. ROC profiling and renal single-cell sequencing highlighted FOS as a specific regulator of podocyte apoptosis in DKD. Molecular docking confirmed stable binding between the four flavonoids and FOS. Experimentally, AS significantly suppressed expression of ECM-related proteins (Col-IV, LN, IL-6, IL-17) and pro-apoptotic proteins (Bax, Caspase-3), while restoring anti-apoptotic Bcl-2 levels and inhibiting phosphorylation of MEK4, JNK1, c-Jun, and FOS in DKD mice. Conclusion: This study elucidates that AS alleviates DKD by inhibiting the MAPK/FOS pathway, thereby attenuating podocyte apoptosis and ECM accumulation. These findings establish a foundation for targeted AS therapy in DKD.", "claims": [{"id": "claim-data-access", "statement": "The original contributions presented in this study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41155564", "locator": "sections[34] \"notes\" paragraph 1", "quote": "The original contributions presented in this study are included in the article/Supplementary Materials. 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