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image of Effect of the Addition of Jujuboside A from Semen Ziziphi Spinosae on Renal Inflammation in Diabetic Mice

Abstract

Background

Diabetic Nephropathy (DN) is a Chronic Kidney Disease (CKD), and its main pathological changes are renal tubular injury and glomerulosclerosis. (SZS) is the seed of var. (Bunge) Hu ex H.F. Chow. As a triterpene saponin, Jujuboside A (Ju A) is the main active substance isolated from SZS. This study sought to investigate the potential effect and mechanism of Jujuboside A against DN.

Methods

The anti-apoptotic effects of Ju A on renal parenchymal cells of DN were examined by in and in studies. Molecular docking and Molecular Dynamics (MD) simulation revealed that Ju A could bind to TNF-α and Caspase-3 forming stable receptor-ligand complexes, respectively. Immunofluorescence (IF) staining and ELISA detection were carried out to investigate the potential mechanisms by which Ju A exerted its amelioration effect on DN.

Results

Our study showed that, accompanied by the restored renal function, Ju A inhibited apoptosis of renal tubules and glomeruli in and in . Network pharmacology revealed that 42 overlapping targets were related to Ju A and DN. Among them, IL6, IL1B, TNF, VEGFA, EGFR, ALB, IGF1, FGF2, CASP3, and ESR1 were the top 10 targets. Ju A could bind to TNF-α and Caspase-3 forming stable receptor-ligand complexes, respectively, as demonstrated by molecular docking and MD simulation. Ju A decreased the protein levels of TNF-α and IL-1β in renal tubules and glomeruli of diabetic mice, and in HG-cultured HK-2 cells and podocytes, leading to the alleviation of inflammation. Besides, the up-regulated relative phosphorylation levels of NF-κB p65 and cleaved caspase-3 were also down-regulated by Ju A and .

Discussion

The research showed that Ju A had a high affinity for Caspase-3 and TNF-α, and the underlying mechanism of Ju A against DN was the inhibition of apoptosis in renal tubular epithelial cells and podocytes. These findings strengthened the evidence that Ju A could be a potential treatment strategy for DN and offered opportunities for therapeutic advances in the field.

Conclusion

Ju A could inhibit apoptosis and alleviate inflammation of renal parenchymal cells by inactivating the TNF-α/NF-κB p65/Caspase-3 signaling pathway, exerting renal protective effect against DN.

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2026-01-07
2026-01-27

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Effect of the Addition of Jujuboside A from Semen Ziziphi Spinosae on Renal Inflammation in Diabetic Mice
Bentham Science Publishers ; https://doi.org/10.2174/0113816128367936251020114651
/content/journals/cpd/10.2174/0113816128367936251020114651
/content/journals/cpd/10.2174/0113816128367936251020114651
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  • Article Type:     Research Article
Keywords: Jujuboside A ; TNF-α ; apoptosis ; modern pharmacology ; diabetic nephropathy ; caspase-3

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