Repurposing the familiar: Future treatment options against chronic kidney disease

Journal of Pharmacy and Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Chronic kidney disease (CKD) is a serious health issue with rising morbidity and mortality rates. Despite advances in understanding its pathophysiology, effective therapeutic options are limited, necessitating innovative treatment approaches. Also, current frontline treatments that available against CKD not uniformly often come significant side effects. Therefore, identifying new targets or improving existing for crucial. Drug repurposing promising strategy the drug discovery process involves screening approved drugs applications. This review discusses pharmacological mechanisms clinical evidence support efficacy of these repurposed drugs. Various classes such as inodilators, endothelin-1 type A (ET-1A) receptor antagonists, bisphosphonates, mineralocorticoid (MR) DNA demethylating agents, nuclear factor erythroid 2-related 2 (NRF2) activators, P2X7 inhibitors, autophagy modulators, hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHI) discussed could remarkably contribute CKD. The critically examines potential well-established to slow progression enhance patient outcomes. emphasizes importance multidisciplinary approach advancing field repurposing, ultimately paving way therapies patients suffering from

Language: Английский

---

Integrated UPLC-ESI-MS/MS, network pharmacology, and transcriptomics to reveal the material basis and mechanism of Schisandra chinensis Fruit Mixture against diabetic nephropathy

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 19, 2025

It has been regarded as an essential treatment option for diabetic nephropathy (DN) in Traditional Chinese medicine. Previous studies have demonstrated the anti-DN efficacy of Schisandra chinensis Fruit Mixture (SM); however, a comprehensive chemical fingerprint is still uncertain, and its mechanism action, especially potential therapeutic targets anti-DN, needs to be further elucidated. Potential mechanisms SM action on DN were explored through network pharmacology experimental validation. The composition was analyzed using UPLC-ESI-MS/MS technology. Active bioactive components identified TCMSP, SwissDrugDesign, SymMap platforms. Differentially expressed genes determined microarray gene data from GSE30528 dataset. Related obtained online databases, which include GeneCards, OMIM DisGeNET. PPI networks compound-target-pathway constructed Cytoscape. Functional annotation performed R software GO enrichment KEGG pathway analysis. model built validation high-sugar high-fat diet combined with STZ induction. Hub critical signaling pathways detected qPCR, Western blotting immunofluorescence. Utilizing coupling technique, analysis 1281 SM's ethanol extract, 349 these recognized compounds pharmacology. Through this analysis, 126 shared 15 HUB pinpointed. Of these, JAK2 most gene. Enrichment revealed that primarily operates within PI3K/AKT pathway. In vivo experiments confirmed improved pathological injury renal function rats while improving mitochondrial morphology modulating expression proteins linked apoptosis (cleaved-caspase-3, Bax, Bcl-2) pro-inflammatory factors (IL-6 TNF-α). Mechanistically, alleviates by suppressing PI3K/AKT/mTOR JAK2/STAT3 fulfill energy tissues. Furthermore, molecular docking provided direct findings. findings study offer initial indications active component robust anti-inflammatory anti-apoptotic characteristics mitigation DN, along capacity safeguard integrity functionality mitochondria. This research unequivocally validates favorable effects SM, indicating viable pharmaceutical agent management DN.

Language: Английский

---

Pathomechanisms of Diabetic Kidney Disease

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(23), P. 7349 - 7349

Published: Nov. 27, 2023

The worldwide occurrence of diabetic kidney disease (DKD) is swiftly rising, primarily attributed to the growing population individuals affected by type 2 diabetes. This surge has been transformed into a substantial global concern, placing additional strain on healthcare systems already grappling with significant demands. pathogenesis DKD intricate, originating hyperglycemia, which triggers various mechanisms and pathways: metabolic, hemodynamic, inflammatory, fibrotic ultimately lead renal damage. Within each pathway, several mediators contribute development structural functional changes. Some these mediators, such as inflammatory cytokines, reactive oxygen species, transforming growth factor β are shared among different pathways, leading overlap interaction between them. While current treatment options for have shown advancement over previous strategies, their effectiveness remains somewhat constrained patients still experience residual risk progression. Therefore, comprehensive grasp molecular underlying onset progression imperative continued creation novel groundbreaking therapies this condition. In review, we discuss achievements in fundamental research, particular emphasis individual factors recent developments treatment.

Language: Английский

---

Mechanisms and therapeutic prospect of the JAK-STAT signaling pathway in liver cancer

Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 480(1), P. 1 - 17

Published: March 22, 2024

Language: Английский

---

Macrophage colony-stimulating factor and its role in the tumor microenvironment: novel therapeutic avenues and mechanistic insights

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: April 4, 2024

The tumor microenvironment is a complex ecosystem where various cellular and molecular interactions shape the course of cancer progression. Macrophage colony-stimulating factor (M-CSF) plays pivotal role in this context. This study delves into biological properties functions M-CSF regulating tumor-associated macrophages (TAMs) its modulating host immune responses. Through specific binding to receptor 1 (CSF-1R), orchestrates cascade downstream signaling pathways modulate macrophage activation, polarization, proliferation. Furthermore, extends influence other cell populations, including dendritic cells. Notably, heightened expression within often associated with dismal patient prognoses. Therefore, comprehensive investigation roles growth advances our comprehension development mechanisms unveils promising novel strategies approaches for treatment.

Language: Английский

---

Advancements in Diabetic Kidney Disease Management: Integrating Innovative Therapies and Targeted Drug Development

AJP Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 326(6), P. E791 - E806

Published: April 17, 2024

Diabetic kidney disease (DKD) is a leading cause of chronic and affects approximately 40% individuals with diabetes . Cases DKD continue to rise globally as the prevalence mellitus increases, an estimated 415 million people living in 2015 projected 642 by 2040. associated significant morbidity mortality, representing 34% 36% all deaths men women, respectively. Common comorbidities including hypertension ageing-related nephron loss further complicate diagnosis progression. The progression involves several mechanisms glomerular endothelial cell dysfunction, inflammation, fibrosis. Targeting these has formed basis therapeutic agents. Renin-angiotensin-aldosterone system (RAAS) blockers, specifically angiotensin receptor blockers (ARBs), demonstrate reductions macroalbuminuria. Sodium-glucose transporter type 2 (SGLT-2) inhibitors protection independent control while also decreasing incidence cardiovascular events. Emerging agents glucagon-like peptide 1 (GLP-1) agonists, anti-inflammatory like bardoxolone, mineralocorticoid antagonists show promise mitigating Many novel therapies monoclonal antibodies CSL346, lixudebart, tozorakimab; mesenchymal stem/stromal infusion; cannabinoid-1 inverse agonism via INV-202 are currently clinical trials present opportunities for drug development.

Language: Английский

---

A new strategy for Astragaloside IV in the treatment of diabetic kidney disease: Analyzing the regulation of ferroptosis and mitochondrial function of renal tubular epithelial cells

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 141, P. 112794 - 112794

Published: Aug. 12, 2024

Language: Английский

---

Critical Analysis of Hot Topics in Diabetic Nephropathy related Experimental Research: A Bibliometric Analysis From 2018 to 2024

Journal of Tissue Viability, Journal Year: 2025, Volume and Issue: 34(1), P. 100854 - 100854

Published: Jan. 5, 2025

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and leading cause end-stage renal disease worldwide. Understanding trends in experimental research on DN crucial for advancing knowledge clinical management. This study aimed to explore current related research, utilizing CiteSpace, VOSviewer, Bibliometrix identify key contributors, influential countries, noteworthy topics. The objective was provide valuable insights healthcare professionals researchers the field. Relevant publications from Web Science Core Collection Citation Index Expanded were retrieved period between 2018 2024. employed data analysis, including identifying top authors, institutions, keywords, co-cited journals, references, trends. A total 1501 relevant articles included study. exhibited an upward trend, reaching its peak 2023. Key contributors such as Kretzler Matthias, Li Ping, Rossing Peter emerged. China, United States Japan have most publications. Keyword analysis revealed "activated protein kinase" central keyword, while "diabetic nephropathy" had highest citation rate. Recent focus shifted towards keywords like "Traditional Chinese Medicine" "molecular docking." bibliometric provides into Notable countries identified, emphasizing global collaboration. topics demonstrate diverse approaches emerging trends, supporting informed decision-making innovation combatting enhancing patient outcomes.

Language: Английский

---

Butyrolactone I blocks the transition of acute kidney injury to chronic kidney disease in mice by targeting JAK1

MedComm, Journal Year: 2025, Volume and Issue: 6(2)

Published: Jan. 21, 2025

Abstract Chronic kidney disease (CKD) is a that affects more than 850 million people. Acute injury (AKI) common cause of CKD, and blocking the AKI–CKD transition shows promising therapeutic potential. Herein, we found butyrolactone I (BLI), natural product, exerts significant nephroprotective effects, including maintenance function, inhibition inflammatory response, prevention fibrosis, in both folic acid‐ ureteral obstruction‐induced mouse models. Notably, BLI showed greater blood urea nitrogen reduction anti‐inflammatory effects telmisartan. Bioinformatics analysis target confirmation assays suggested directly binds to JAK1, kinase assay confirmed it potent JAK1inhibitor with an IC 50 0.376 µM. Experiments JAK1‐knockdown mice also proved targets JAK1 work. Furthermore, demonstrated safety comparable ivarmacitinib, well‐known inhibitor. Mechanistically, inhibits its phosphorylation JAK‐STAT activation, subsequently regulating downstream signaling pathways inhibit reactive oxygen species production, inflammation, ferroptosis, thereby preventing occurrence fibrosis process. This study demonstrates for first time inhibitor candidate delaying CKD progression, which warrants further investigation.

Language: Английский

---

Potential Modulatory Effects of Hesperidin on the JAK/STAT Pathway in Mesangial Proliferative Glomerulonephritis

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(2)

Published: Feb. 1, 2025

ABSTRACT Mesangial proliferative glomerulonephritis (MsPGN) is a common type of glomerular disease characterized by immune complex deposition and inflammation in the kidney, leading to renal dysfunction. Currently, treatment options for MsPGN are limited, there need effective therapeutic interventions. Hesperidin (HSP), natural flavonoid glycoside, has shown promising anti‐inflammatory antioxidant properties various models. This study aimed investigate potential HSP explore its possible mechanism action. A male Wistar rat model was established via tail vein injection Thy‐1 monoclonal antibody, rats were divided into four groups: Control, MsPGN, + HSP, Prednisone. After 7 days intervention, effects evaluated through biochemical histological analyses. Our results demonstrated that significantly reduced levels blood urea nitrogen, serum creatinine, total cholesterol, triglycerides, improved pathology. Additionally, pro‐inflammatory cytokines, including tumor necrosis factor‐α, interleukin‐1β, interleukin‐2, monocyte chemoattractant protein‐1, markedly decreased. Immunofluorescence analysis revealed immunoglobulin G C5b‐9, along with decreased kidneys. Furthermore, downregulated phosphorylation Janus kinase 2 (JAK2) signal transducer activator transcription 3 (STAT3), suggesting modulation JAK/STAT pathway. In conclusion, might effectively alleviate injury, reduce inflammatory response, inhibit deposition, potentially suppression

Language: Английский

---