ArticleInternational journal of molecular sciences2020
Multiple-Purpose Connectivity Map Analysis Reveals the Benefits of Esculetin to Hyperuricemia and Renal Fibrosis.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 20 citations in OpenAlex.
- Limosilactobacillus fermentum M5e Attenuates Hyperuricemia and Renal Injury via Dual Modulation of Gut Microbiota and Purine Metabolic Pathways.ACS pharmacology & translational science · 2025Article
- Therapeutic potential and pharmacological mechanisms of Traditional Chinese Medicine in gout treatment.Acta pharmacologica Sinica · 2025Review
- Renal interstitial fibrotic assessment using non-Gaussian diffusion kurtosis imaging in a rat model of hyperuricemia.BMC medical imaging · 2024Article
- PC3T: a signature-driven predictor of chemical compounds for cellular transition.Communications biology · 2023Article
- TCM and related active compounds in the treatment of gout: the regulation of signaling pathway and urate transporter.Frontiers in pharmacology · 2023Review
- New insight into the management of renal excretion and hyperuricemia: Potential therapeutic strategies with natural bioactive compounds.Frontiers in pharmacology · 2022Review
- Prediction of drug efficacy from transcriptional profiles with deep learning.Nature biotechnology · 2021Article
- LPCAT1 overexpression promotes the progression of hepatocellular carcinoma.Cancer cell international · 2021Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Hyperuricemia (HUA) is a risk factor for chronic kidney disease (CKD). Serum uric acid (SUA) levels in CKD stage 3-4 patients closely correlate with hyperuricemic nephropathy (HN) morbidity. New uric acid (UA)-lowering strategies are required to prevent CKD. The multiple-purpose connectivity map (CMAP) was used to discover potential molecules against HUA and renal fibrosis. We used HUA and unilateral ureteral occlusion (UUO) model mice to verify renoprotective effects of molecules and explore related mechanisms. In vitro experiments were performed in HepG2 and NRK-52E cells induced by UA. Esculetin was the top scoring compound and lowered serum uric acid (SUA) levels with dual functions on UA excretion. Esculetin exerted these effects by inhibiting expression and activity of xanthine oxidase (XO) in liver, and modulating UA transporters in kidney. The mechanism by which esculetin suppressed XO was related to inhibiting the nuclear translocation of hexokinase 2 (HK2). Esculetin was anti-fibrotic in HUA and UUO mice through inhibiting TGF-β1-activated profibrotic signals. The renoprotection effects of esculetin in HUA mice were associated with lower SUA, alleviation of oxidative stress, and inhibition of fibrosis. Esculetin is a candidate urate-lowering drug with renoprotective activity and the ability to inhibit XO, promote excretion of UA, protect oxidative stress injury, and reduce renal fibrosis.
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