Content: 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 and 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 downregulated 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. Upregulation of lncRNA SNHG10 also improved DN in mice. Meanwhile, downregulation of SNHG10 reversed the effects of xanthohumol on HG-induced HK-2 cells. Additionally, miR-378b directly targeted lncRNA SNHG10.
Conclusion and discussion: 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: SNHG10/miR-378b; diabetic nephropathy; inflammatory response; interstitial fibrosis; renal fibrosis; xanthohumol.
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