Abstract：
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.
We aim to provide a systematic overview of the mechanisms of Sch in multiple pathways to treat DN in rats.
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.
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.
Sch functions by relieving oxidative stress and the inflammatory response by regulating Crb3, Xaf1, and Tspan4 protein expression levels to treat DN disease.
We aim to provide a systematic overview of the mechanisms of Sch in multiple pathways to treat DN in rats.
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.
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.
Sch functions by relieving oxidative stress and the inflammatory response by regulating Crb3, Xaf1, and Tspan4 protein expression levels to treat DN disease.
摘要：
背景：糖尿病肾病（DN）是糖尿病的主要并发症。五味子乙素（Sch）是一种天然药物单体，可预防糖尿病引起的肾脏损害并恢复其功能。然而,对Sch治疗DN的作用机制尚缺乏全面系统的认识。
目的：我们旨在系统概述Sch在多种途径中治疗大鼠DN的机制。
方法：用链脲佐菌素建立DN大鼠模型，用Sch进一步治疗。使用网络药理学预测了Sch对DN的保护作用的可能机制，并通过定量蛋白质组学分析进行了验证。
结果：大剂量Sch治疗显著下调空腹血糖，肌酐,血尿素氮,DN大鼠肾小球和肾小管间质中的尿蛋白水平和胶原蛋白沉积减少。Sch治疗可显著提高DN大鼠肾脏超氧化物歧化酶(SOD)和血浆谷胱甘肽过氧化物酶(GSH-Px)的活性。此外,IL-6，IL-1β，在接受Sch治疗的DN大鼠中，TNF-α显着降低。靶向Sch和DN的11种蛋白质在MAPK信号通路中富集，PI3K-Akt信号,肾细胞癌，间隙连接,内分泌抵抗，和TNF信号。此外，定量蛋白质组学表明，Xaf1在模型中下调对照组和上调的Sch治疗vs.模型组。五种蛋白质,发现Crb3，Tspan4，Wdr45，Zfp512和Tmigd1在模型中与对照组和下调的Schvs.模型组。网络药理学预测和蛋白质组学结果之间的三个交叉蛋白，鉴定了Crb3、Xaf1和Tspan4。
结论：Sch通过调节Crb3、Xaf1和Tspan4蛋白表达水平缓解氧化应激和炎症反应来治疗DN疾病。
目的：我们旨在系统概述Sch在多种途径中治疗大鼠DN的机制。
方法：用链脲佐菌素建立DN大鼠模型，用Sch进一步治疗。使用网络药理学预测了Sch对DN的保护作用的可能机制，并通过定量蛋白质组学分析进行了验证。
结果：大剂量Sch治疗显著下调空腹血糖，肌酐,血尿素氮,DN大鼠肾小球和肾小管间质中的尿蛋白水平和胶原蛋白沉积减少。Sch治疗可显著提高DN大鼠肾脏超氧化物歧化酶(SOD)和血浆谷胱甘肽过氧化物酶(GSH-Px)的活性。此外,IL-6，IL-1β，在接受Sch治疗的DN大鼠中，TNF-α显着降低。靶向Sch和DN的11种蛋白质在MAPK信号通路中富集，PI3K-Akt信号,肾细胞癌，间隙连接,内分泌抵抗，和TNF信号。此外，定量蛋白质组学表明，Xaf1在模型中下调对照组和上调的Sch治疗vs.模型组。五种蛋白质,发现Crb3，Tspan4，Wdr45，Zfp512和Tmigd1在模型中与对照组和下调的Schvs.模型组。网络药理学预测和蛋白质组学结果之间的三个交叉蛋白，鉴定了Crb3、Xaf1和Tspan4。
结论：Sch通过调节Crb3、Xaf1和Tspan4蛋白表达水平缓解氧化应激和炎症反应来治疗DN疾病。
