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Phytomedicine

Phytomedicine

IF: 6.7
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Quercetin ameliorates renal injury by promoting UCP1-mediated alleviation of lipid accumulation in diabetic kidney disease

Published:27 August 2025 DOI: 10.1016/j.phymed.2025.157213
Wei Yong , Ziyi Li , Weilong Xu , Danni Gao , Baixue Sha , Yinuo Jin , Yumeng Shen , Yanfeng Zhang , Yi Pan , Jianxing Liu , Fangfang Zhang , Jiangyi Yu , Liang Jin , Yue Yang

Abstract

Background

Diabetic kidney disease (DKD) represents a common microvascular complication associated with diabetes. Research suggests that lipid accumulation contributes to lipotoxicity, exacerbating kidney injury in DKD. Quercetin (QCT), a flavonoid derived from specific fruits and vegetables, has shown potential in mitigating DKD progression; however, its precise protective mechanisms remain to be explored.

Purpose

This study aimed to explore the effects of quercetin (QCT) on lipid accumulation in DKD and elucidate the underlying mechanisms.

Methods

The pathological and molecular changes associated with DKD were examined through histological, biochemical, and transcriptomic analyses in DKD mice and cell models treated with QCT. Bioinformatics analysis was conducted to identify key targets of QCT in DKD treatment. Molecular docking, cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) were utilized to confirm the interaction of QCT and the identified targets. Moreover, PPARA/PPARG inhibitors and si-UCP1 were co-incubated with QCT in DKD cell models to assess their regulatory roles.

Results

QCT significantly improved renal function, reduced lipid deposition, and mitigated renal fibrosis in DKD mice. Peroxisome proliferator-activated receptors alpha and gamma (PPARA and PPARG) were identified as critical targets of QCT in DKD treatment. Inhibition of PPARA and PPARG in HK-2 cells reduced the protective effects of QCT. Transcriptomic analysis revealed that QCT activated the PPARA/PPARG-UCP1 axis, enhancing fatty acid oxidation, decreasing reactive oxygen species (ROS) production, and alleviating lipotoxicity.

Conclusions

QCT ameliorated renal injury in DKD by improving lipid accumulation via the PPARA/PPARG-UCP1 axis, highlighting its potential as a therapeutic option for DKD treatment.

Substances (10)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Quercetin 117-39-5 C15H10O7 816 suppliers $5.00-$3876.00
Quercetin 117-39-5 C15H10O7 816 suppliers $5.00-$3876.00
Quercetin 117-39-5 C15H10O7 816 suppliers $5.00-$3876.00
Quercetin 117-39-5 C15H10O7 816 suppliers $5.00-$3876.00
Losartan 114798-26-4 C22H23ClN6O 305 suppliers $6.00-$1946.00
Losartan 114798-26-4 C22H23ClN6O 305 suppliers $6.00-$1946.00
Losartan 114798-26-4 C22H23ClN6O 305 suppliers $6.00-$1946.00
Losartan 114798-26-4 C22H23ClN6O 305 suppliers $6.00-$1946.00
Quercetin 117-39-5 C15H10O7 - Inquiry
Quercetin 117-39-5 C15H10O7 - Inquiry

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