ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Renal Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1532517
Xanthohumol ameliorates diabetic kidney disease through suppression of renal fibrosis by regulating SNHG10/miR-378b
Provisionally accepted
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, China
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Diabetic kidney disease (DKD), commonly termed diabetic nephropathy (DN), is characterized by oxidative stress and renal tubular epithelial cells apoptosis driven by high glucose (HG). Objective: To explore the protective effects and underlying mechanism of xanthohumol in DN mice and HG-induced HK-2 cells. Materials & methods: The STZ-treated mice and HG stimulated HK-2 cells were applied to establish in vivo and in vitro DN models. The concentrations of blood glucose, serum creatinine, BUN and urine creatinine, and β-n-acetylglucosaminidase (NAG) activity was determined. The pathological changes of renal tissues were evaluated by Masson and periodic acid schiff (PAS) staining. TNF-α, IL-1β and IL-6 levels were detected using ELISA. Furthermore, CCK-8 assay and flow cytometer analysis were applied for determining HK-2 cells viability and apoptosis, respectively. Gene and protein levels was evaluated by qRT-PCR analysis and western blot/IHC. The relationship between lncRNA SNHG10 and miR-378b was confirmed by luciferase reporter assay. Results: Xanthohumol effectively improves DN-stimulated kidney structural and functional abnormalities. LncRNA SNHG10 was down-regulated in the renal tissues of DN mice and HG induced HK-2 cells, while this inhibition was reversed by xanthohumol treatment. We also noted that xanthohumol remarkably reversed HG induced HK-2 cells injury. Up-regulation of lncRNA SNHG10 also improved DN in mice. Meanwhile, down-regulation of SNHG10 reversed the effects of xanthohumol on HG-induced HK-2 cells. Additionally, miR-378b directly targeted lncRNA SNHG10.Xanthohumol inhibited the progression of DN by regulating SNHG10/miR-378b, indicating a novel understanding of xanthohumol in DN progression and providing a latent therapeutic target for DN therapy.
Keywords: Xanthohumol, diabetic nephropathy, renal fibrosis, SNHG10/miR-378b, interstitial fibrosis, Inflammatory Response
Received: 22 Nov 2024; Accepted: 30 Apr 2025.
Copyright: © 2025 Hao, Li and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jian Hao, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, China
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