Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Introduction: Large prospective trials have demonstrated that finerenone could reduce the risk of cardiovascular death and progression of renal failure among patients with chronic kidney disease associated heart failure and/or type 2 diabetes mellitus (T2DM). The aim of this study was to explore the molecular mechanism of finerenone in the treatment of cardiorenal diseases through network pharmacology.
Methods: The STITH, SwissTargetPrediction, PharmMapper, DrugBank, and ChEMBL databases were used to screen the targets of finerenone. The disease-related targets were retrieved from the DisGeNET, GeneCards, CTD, OMIM, and MalaCards databases. The protein-protein interaction (PPI) network was conducted with STRING database and Cytoscape software. The clusterProfiler R package was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The interactions of key targets and finerenone were analyzed by molecular docking in Autodock software. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. Histopathology of myocardial and renal tissues was observed by hematoxylin-eosin (HE) staining, and detection of protein expressions was conducted using Western blotting.
Results: A total of 111 potential cardiorenal targets of finerenone were identified. The main mechanisms of action may be associated with lipids and atherosclerosis, fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, and diabetic cardiomyopathy. The hub targets demonstrated by the PPI network were CASP3, ALB, MMP9, EGFR, ANXA5, IGF1, SRC, TNFRSF1A, IL2, and PPARG, and the docking results suggested that finerenone could bind to these targets with high affinities. HE staining revealed the cardiorenal protection of finerenone on diabetic mice. In addition, the protein expressions of CASP3 and EGFR were increased while ALB was decreased in myocardial and renal tissues in diabetic mice compared with control mice, which were reversed by finerenone.
Conclusion: This study suggested that finerenone exerts cardiorenal benefits through multiple targets and pathways.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1159/000539393 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Nonsteroidal and Steroidal Mineralocorticoid Antagonists: Rationale, Evidence, and Unanswered Questions.
JACC Heart Fail
August 2025
Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri, USA. Electronic address:
Steroidal mineralocorticoid receptor antagonists (MRAs), such as spironolactone and eplerenone, have demonstrated substantial benefits in randomized controlled trials for patients with heart failure with reduced ejection fraction. However, their effectiveness in heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction remains uncertain, and the implementation of this class has remained low, in part due to its side effects and tolerability profile. Emerging therapies that target the mineralocorticoid receptor and/or the production of aldosterone may offer alternative strategies to treat the aldosterone-mineralocorticoid receptor axis.
View Article and Find Full Text PDFDiabetic kidney disease: from pathogenesis to multimodal therapy-current evidence and future directions.
Front Med (Lausanne)
August 2025
Department of Nephrology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China.
Diabetic kidney disease (DKD) has emerged as the leading cause of chronic kidney disease (CKD) worldwide, surpassing primary glomerular disorders in prevalence. Despite recent therapeutic advances, current treatment strategies primarily alleviate symptoms rather than address the underlying pathogenic mechanisms, highlighting an urgent need for targeted, mechanism-based interventions. The pathogenesis of DKD involves a complex interplay of metabolic, hemodynamic, inflammatory, oxidative, and fibrotic pathways.
View Article and Find Full Text PDFHuangkui capsule combined with finerenone attenuates diabetic nephropathy by regulating the JAK2/STAT3 signaling pathway based on network pharmacology, molecular docking, and experimental verification.
Front Pharmacol
August 2025
Department of Nephrology, The First Affiliated Hospital of Shihezi University, Shihezi, China.
Introduction: Diabetic nephropathy (DN) is a serious complication of diabetes with limited therapeutic options. Although Huangkui capsule (HKC) and finerenone individually show potential in DN management, their combined mechanism remains unclear. This study aimed to explore the therapeutic effects and underlying mechanisms of HKC and finerenone combination for DN.
View Article and Find Full Text PDFThe multi-target intervention reveals the mechanism by which Finerenone alleviates Polymyxin B-induced kidney injury: an integrated study of network pharmacology, transcriptomics, and molecular docking.
Eur J Pharmacol
August 2025
Department of Pharmacy, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, Hubei, 430060, China. Electronic address:
Background: Polymyxin B (PMB), a last-resort antibiotic against multidrug-resistant Gram-negative pathogens, faces clinical limitations due to dose-dependent nephrotoxicity. Current protective strategies have proven inadequate, underscoring an urgent need for novel interventions. We hypothesize that Finerenone may mitigate PMB-induced kidney injury through multi-mechanism renoprotective effects.
View Article and Find Full Text PDFPharmacology and Therapeutic Potential of Finerenone: A Novel Third-Generation Nonsteroidal Mineralocorticoid Receptor Antagonist.
Cureus
July 2025
Department of Diabetes and Endocrinology, Khartoum North Teaching Hospital, Khartoum, SDN.
Finerenone is a novel third-generation nonsteroidal mineralocorticoid receptor antagonist (MRA) that has demonstrated efficacy in treating chronic kidney disease (CKD) and heart failure with reduced ejection fraction (HFrEF). Unlike traditional steroidal MRAs such as Spironolactone and Eplerenone, Finerenone offers high selectivity for MR, resulting in reduced off-target effects, including hyperkalemia and antiandrogenic side effects. It exerts renoprotective and cardioprotective effects through its anti-inflammatory and antifibrotic actions, making it a good therapeutic option for patients with CKD and HFrEF.
View Article and Find Full Text PDF