ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1656409
This article is part of the Research TopicBioinformatics and Beyond: Exploring the Health Benefits of Bioactive Metabolites from PlantsView all 4 articles
Scutellarin Attenuated Tubule cell Apoptosis by modulating HIF-1α for the Treatment of DKD: The insight integrating Network analysis, Machine Learning and Single-cell Transcriptome
Provisionally accepted
- 1China-Japan Friendship Hospital, Beijing, China
- 2Beijing Dongcheng District Center for Disease Control and Prevention, Beijing, China
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Aim To explore the possible mechanism and target of scutellarin (Scu) on diabetic kidney disease(DKD). Method The Network analysis was used to explore and enrich the possible pathway. RNA transcriptome were employed to deepen the understanding of candidate targets in key signaling pathways. Core targets were optimized through 8 machine learning algorithms. Single-cell transcriptome were utilized to clarify the expression locations and temporal trajectories of core targets, identifying high-expression cell types. Finally, molecular docking and cell experiments were conducted to validate the regulatory effects of Scutellarin on the molecular targets. Result The Network analysis showed the roles of hypoxic response and apoptosis pathways. RNA transcriptome and machine learning identified HIF-1α and CASP3 as the hub genes related to DKD outcomes and hypoxic apoptosis. Single-cell transcriptome analysis confirmed the expression patterns and locations of hub genes, identifying the CD-PC cells as the high-expression cell type. In-vitro experiments demonstrated 20 μM scutellarin was most beneficial for mIMCD-3 cell proliferation. The hypoxia significantly enhanced HIF-1α gene transcription driven by HRE conserved genes (P < 0.0001), whereas high glucose inhibited hypoxia-induced HIF-1α transcription (P < 0.05). Scutellarin significantly up-regulated HIF-1α transcriptional activity (P < 0.05) and HIF-1α total protein expression under high glucose-hypoxia (P < 0.05), reduced mitochondrial ROS release (P < 0.05) and renal tubular cell apoptosis (P < 0.01). Conclusion Scutellarin attenuated renal collecting duct cell apoptosis by modulating HIF-1α for the treatment of DKD.
Keywords: Diabetic kidney disease, Scutellarin, machine learning, Single-cell transcriptome analysis, Network analysis
Received: 30 Jun 2025; Accepted: 12 Sep 2025.
Copyright: © 2025 Jiang, Jian, Zhang and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Li Jiang, China-Japan Friendship Hospital, Beijing, China
Xiai Wu, China-Japan Friendship Hospital, Beijing, China
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