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Frontiers in Pharmacology

Frontiers in Pharmacology

IF: 4.4
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Quercetin ameliorates renal injury in hyperuricemic rats via modulating ER stress pathways

Published:2 September 2025 DOI: 10.3389/fphar.2025.1660599 PMID: 40963680
Huan Liu,?Qi Yang,?Shuiying Wang,?Tingting Wang,?Lihua Pan,?Xue Wang,?Yangfeng Chi,?Zhouhui Jin

Abstract

Hyperuricemia is a key risk factor for chronic kidney disease (CKD), yet effective treatments remain limited. This study demonstrates that quercetin exerts potent renoprotective effects in hyperuricemia-induced CKD through multifaceted mechanisms. In rats with hyperuricemia induced by adenine (0.1?g/kg) and potassium oxonate (1.5?g/kg), quercetin treatment (50 or 100?mg/kg) significantly improved renal function by reducing urinary ACR, serum creatinine, uric acid, BUN, and blood pressure, while alleviating renal inflammation, fibrosis, and crystal deposition. Mechanistic studies revealed quercetin's ability to suppress ER stress markers (GRP78, CHOP, p-PERK, IRE1α, ATF6), inhibit renal GLUT9 expression, and downregulate downstream inflammatory (TLR4/NF-κB/IL-1β/TNF-α), fibrotic (collagen I/α-SMA/fibronectin), and oxidative pathways, while enhancing antioxidant defenses and inhibiting apoptosis. Notably, quercetin showed superior efficacy to febuxostat (5?mg/kg), the clinical gold standard. These findings establish quercetin as a promising therapeutic candidate for hyperuricemia-associated kidney injury through its comprehensive modulation of ER stress-mediated pathological processes.

Substances (22)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Adenine 73-24-5 C5H5N5 1165 suppliers $6.00-$3200.00
Adenine 73-24-5 C5H5N5 1165 suppliers $6.00-$3200.00
Adenine 73-24-5 C5H5N5 1165 suppliers $6.00-$3200.00
Adenine 73-24-5 C5H5N5 1165 suppliers $6.00-$3200.00
Febuxostat 144060-53-7 C16H16N2O3S 957 suppliers $5.00-$5690.00
Febuxostat 144060-53-7 C16H16N2O3S 957 suppliers $5.00-$5690.00
Febuxostat 144060-53-7 C16H16N2O3S 957 suppliers $5.00-$5690.00
Febuxostat 144060-53-7 C16H16N2O3S 957 suppliers $5.00-$5690.00
Quercetin 117-39-5 C15H10O7 802 suppliers $5.00-$3876.00
Quercetin 117-39-5 C15H10O7 802 suppliers $5.00-$3876.00

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