Quantitative Proteomics Combined with Network Pharmacology Analysis Unveils the Biological Basis of Schisandrin B in Treating Diabetic Nephropathy


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Background:Diabetic nephropathy (DN) is a major complication of diabetes. Schisandrin B (Sch) is a natural pharmaceutical monomer that was shown to prevent kidney damage caused by diabetes and restore its function. However, there is still a lack of comprehensive and systematic understanding of the mechanism of Sch treatment in DN.

Objective:We aim to provide a systematic overview of the mechanisms of Sch in multiple pathways to treat DN in rats.

Methods:Streptozocin was used to build a DN rat model, which was further treated with Sch. The possible mechanism of Sch protective effects against DN was predicted using network pharmacology and was verified by quantitative proteomics analysis.

Results:High dose Sch treatment significantly downregulated fasting blood glucose, creatinine, blood urea nitrogen, and urinary protein levels and reduced collagen deposition in the glomeruli and tubule-interstitium of DN rats. The activities of superoxide dismutase (SOD) and plasma glutathione peroxidase (GSH-Px) in the kidney of DN rats significantly increased with Sch treatment. In addition, the levels of IL-6, IL-1β, and TNF-α were significantly reduced in DN rats treated with Sch. 11 proteins that target both Sch and DN were enriched in pathways such as MAPK signaling, PI3K-Akt signaling, renal cell carcinoma, gap junction, endocrine resistance, and TNF signaling. Furthermore, quantitative proteomics showed that Xaf1 was downregulated in the model vs. control group and upregulated in the Sch-treated vs. model group. Five proteins, Crb3, Tspan4, Wdr45, Zfp512, and Tmigd1, were found to be upregulated in the model vs. control group and downregulated in the Sch vs. model group. Three intersected proteins between the network pharmacology prediction and proteomics results, Crb3, Xaf1, and Tspan4, were identified.

Conclusion:Sch functions by relieving oxidative stress and the inflammatory response by regulating Crb3, Xaf1, and Tspan4 protein expression levels to treat DN disease.

Sobre autores

Jianying Song

School of Life Sciences, Tianjin University

Email: info@benthamscience.net

Bo Zhang

Institute for TCM-X, MOE Key Laboratory of Bioinformatics, Bioinformatics Division, BNRist, Department of Automation, Tsinghua University

Email: info@benthamscience.net

Huiping Zhang

, Shanghai Applied Protein Technology Co., Ltd.

Email: info@benthamscience.net

Wenbo Cheng

, Tianjin Key Laboratory of Medical Mass Spectrometry for Accurate Diagnosis

Autor responsável pela correspondência
Email: info@benthamscience.net

Peiyuan Liu

School of Life Sciences, Tianjin University

Autor responsável pela correspondência
Email: info@benthamscience.net

Jun Kang

School of Life Sciences, Tianjin University

Autor responsável pela correspondência
Email: info@benthamscience.net

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