ArticleInternational journal of molecular sciences2025
Spinach Extract Reduces Kidney Damage in Diabetic Rats by Impairing the AGEs/RAGE Axis.
Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Plant-Derived Spinacetin Mitigates Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats.International journal of molecular sciences · 2026Article
- Exploring the Mechanism of Therapeutic Effects of Polydatin in Lung Ischemia-Reperfusion Injury by Network Pharmacology and Experiment Validation.Journal of inflammation research · 2026Article
- Inflammation, Apoptosis, and Fibrosis in Diabetic Nephropathy: Molecular Crosstalk in Proximal Tubular Epithelial Cells and Therapeutic Implications.Current issues in molecular biology · 2025Review
- Mechanistic Insight into Phenolic Compounds in Mitigating Diabetic Complications Induced by Advanced Glycation End Products.Current issues in molecular biology · 2025Review
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9 authors.
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Abstract
The interaction between advanced glycation end products (AGEs) and their RAGE receptor (AGEs/RAGE axis) triggers several signaling pathways that lead to the development of diabetic nephropathy (DN). One of the most studied AGEs is Nε-(1-Carboxymethyl)-L-lysine (CML).
objectiveWe aimed to investigate the functional role of spinach methanolic extract (SME) on kidney damage in diabetic rats associated with the CML/RAGE axis.
methodsForty adult male Wistar rats were used in this study and divided into four groups: control rats (CTRL), SME-administered CTRL (400 mg/kg; SME), streptozotocin-induced diabetic nephropathy rats (STZ), and SME-treated STZ (STZ-SME); treatments were administered daily. After 12 weeks, serum AGEs, creatinine in urine, and lipid peroxidation in kidneys were measured. The distribution and expression levels of inflammatory and fibrotic mediators and RAGE signaling were evaluated through immunohistochemistry (NOX4, CML, RAGE, nuclear NF-κB, TNF-α, IL-1β, TGF-β1, SMAD2/3, CTGF, and a-SMA) and immunolocalization of CML/RAGE.
resultsGlycoside flavonoid derivatives, such as patuletin and spinacetin, were primarily identified in the extract. Kidneys from the STZ group showed altered morphology, dead cells in the proximal tubules, and increased oxidative stress markers; notably, these effects were improved by SME treatment (STZ-SME). The STZ-SME group showed a lower staining intensity for CML and RAGE, which was associated with a decrease in the expression of inflammatory and fibrotic factors compared with the STZ group. In all groups, the distribution of these markers varied among proximal tubule, glomerular, and interstitial cells.
conclusionsSME treatment may help to prevent or delay kidney damage in diabetic rats by regulating inflammatory and fibrotic processes associated with the AGEs/RAGE pathway, a mechanism involved in the development of nephropathy.
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