ArticleActa pharmacologica Sinica2019
The aldose reductase inhibitor epalrestat exerts nephritic protection on diabetic nephropathy in db/db mice through metabolic modulation.
Article in Acta pharmacologica Sinica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 66 citations in OpenAlex.
- Mechanistic Insights into Aldose Reductase-Dependent Modulation of Hypoxia-Inducible Factor-1α in Promoting Renal Fibrosis.Cell biochemistry and biophysics · 2026Article
- ExploringMolecules (Basel, Switzerland) · 2026Article
- Effects of High Glucose on Simulated Ischemia/Reperfusion Injury in Isolated Cardiomyocytes.International journal of molecular sciences · 2025Article
- Repurposing of epalrestat for neuroprotection in parkinson's disease via activation of the KEAP1/Nrf2 pathway.Journal of neuroinflammation · 2025Article
- Therapeutic effects of mecobalamin combined with epalrestat on diabetic peripheral neuropathy: reduction of inflammatory factors and improvement in electromyogram indices.American journal of translational research · 2025Article
- Aldose Reductase Mediated Mitophagy Promotes Epithelial-Mesenchymal Transition of Hepatocytes.Hepatic medicine : evidence and research · 2025Article
- Dihydroxyacetone phosphate accumulation leads to podocyte pyroptosis in diabetic kidney disease.Journal of cellular and molecular medicine · 2024Article
- Article
- Parallelism and non-parallelism in diabetic nephropathy and diabetic retinopathy.Frontiers in endocrinology · 2024Review
- Novel role for epalrestat: protecting against NLRP3 inflammasome-driven NASH by targeting aldose reductase.Journal of translational medicine · 2023Article
- Astragalin ameliorates renal injury in diabetic mice by modulating mitochondrial quality control via AMPK-dependent PGC1α pathway.Acta pharmacologica Sinica · 2023Article
- Tracer metabolomics reveals the role of aldose reductase in glycosylation.Cell reports. Medicine · 2023Article
- 2'-Hydroxy-4',5'-dimethoxyacetophenone Exhibit Collagenase, Aldose Reductase Inhibition, and Anticancer Activity Against Human Leukemic Cells: An In Vitro, and In Silico Study.Molecular biotechnology · 2023Article
- Epalrestat is effective in treating diabetic foot infection and can lower serum inflammatory factors in patients.American journal of translational research · 2023Article
- A Cyclopentanone Compound Attenuates the Over-Accumulation of Extracellular Matrix and Fibrosis in Diabetic Nephropathy via Downregulating the TGF-β/p38MAPK Axis.Biomedicines · 2022Article
- Potential role of oxidative stress in the pathogenesis of diabetic bladder dysfunction.Nature reviews. Urology · 2022Review
- Syzygium aromaticum bud (clove) essential oil is a novel and safe aldose reductase inhibitor: in silico, in vitro, and in vivo evidence.Hormones (Athens, Greece) · 2022Article
- In Search of Differential Inhibitors of Aldose Reductase.Biomolecules · 2022Review
- Efficacy of epalrestat combined with alprostadil for diabetic nephropathy and its impacts on renal fibrosis and related factors of inflammation and oxidative stress.American journal of translational research · 2022Article
- Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung Carcinoma.Nutrition and metabolic insights · 2022Article
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Authors and funding
12 authors at 4 institutions in 1 country.
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Abstract
Epalrestat is an inhibitor of aldose reductase in the polyol pathway and is used for the management of diabetic neuropathy clinically. Our pilot experiments and accumulated evidences showed that epalrestat inhibited polyol pathway and reduced sorbitol production, and suggested the potential renal protection effects of epalrestat on diabetic nephropathy (DN). To evaluate the protective effect of epalrestat, the db/db mice were used and exposed to epalrestat for 8 weeks, both the physiopathological condition and function of kidney were examined. For the first time, we showed that epalrestat markedly reduced albuminuria and alleviated the podocyte foot process fusion and interstitial fibrosis of db/db mice. Metabolomics was employed, and metabolites in the plasma, renal cortex, and urine were profiled using a gas chromatography-mass spectrometry (GC/MS)-based metabolomic platform. We observed an elevation of sorbitol and fructose, and a decrease of myo-inositol in the renal cortex of db/db mice. Epalrestat reversed the renal accumulation of the polyol pathway metabolites of sorbitol and fructose, and increased myo-inositol level. Moreover, the upregulation of aldose reductase, fibronectin, collagen III, and TGF-β1 in renal cortex of db/db mice was downregulated by epalrestat. The data suggested that epalrestat has protective effects on DN, and the inhibition of aldose reductase and the modulation of polyol pathway in nephritic cells be a potentially therapeutic strategy for DN.
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