Cheng-Hua Zhang, Xiao-Yan Li, Hong-Xiang Zheng, Min Zhao, Mei-Feng Zhu, Shu-Qi Min, Xin-Yue Zhang, Shen-Ju Wang
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Bioinformatics was employed to screen the active components and targets of the decoction and the potential targets of CKD. The protein-protein interaction(PPI) network of the common targets shared by the decoction and CKD and the drug-component-target network were constructed. The core components and targets were screened according to the correlation degree of the network. The binding between core components and targets was verified by molecular docking. The results showed that Sanhuang Hushen Fangshuai Decoction improved the renal function and reduced proteinuria. Compared with the healthy population, the post-treatment population showed recovery of 54 up-regulated metabolites and 43 down-regulated metabolites. Enrichment analysis results showed that the key pathways included adenosine triphosphate binding cassette(ABC) transport, tryptophan metabolism, and tyrosine metabolism. The results of bioinformatics analysis showed that the core components of Sanhuang Hushen Fangshuai Decoction in treating CKD included kaempferol, β-sitosterol, luteolin, 7-O-methylisolingol, and tanshinone Ⅱ_A. The core targets included TP53, PTGS2, JUN, AKT1, and TNF. Molecular docking results showed that the core components bound well to the target genes. The results of joint pathway analysis suggested that both differential metabolites and key targets were involved in galactose metabolism, nicotinamide metabolism, and other pathways. This study suggests that Sanhuang Hushen Fangshuai Decoction is effective for CKD, and it can regulate multiple abnormal metabolites and participates in multiple metabolic pathways involving amino acids and sugars. The active components such as kaempferol in the decoction may regulate related targets such as TP53 and PTGS2. 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引用次数: 0
摘要
本文旨在从代谢组学和生物信息学的角度分析三黄护肾防衰汤治疗慢性肾脏疾病(CKD)的疗效,探讨其作用机制。入选常州市中医院2023年6月至2024年3月诊治的3-4期CKD患者。采用三黄护肾防帅汤治疗,观察疗效。分别采集治疗前后血清样本。采用超高效液相色谱法检测血清代谢物,并进行多元统计分析。采用生物信息学方法筛选该煎剂的有效成分和靶点,以及CKD的潜在靶点。构建了汤剂与CKD共有靶点的蛋白-蛋白相互作用(PPI)网络和药物组分-靶点网络。根据网络的关联度筛选核心组件和目标。通过分子对接验证核心组分与靶点之间的结合。结果显示,三黄护肾防帅汤能改善大鼠肾功能,降低蛋白尿。与健康人群相比,治疗后人群有54种上调代谢物和43种下调代谢物恢复。富集分析结果表明,关键途径包括三磷酸腺苷结合盒(ABC)转运、色氨酸代谢和酪氨酸代谢。生物信息学分析结果显示,三黄护肾防瘫汤治疗CKD的核心成分包括山奈酚、β-谷甾醇、木犀草素、7- o -甲基异黄酮醇和丹参酮Ⅱ_A。核心靶点包括TP53、PTGS2、JUN、AKT1和TNF。分子对接结果表明,核心组分与靶基因结合良好。联合通路分析结果表明,差异代谢物和关键靶点都参与了半乳糖代谢、烟酰胺代谢等通路。本研究提示三黄护肾防衰汤对CKD有效,可调节多种异常代谢物,参与氨基酸、糖等多种代谢途径。汤中山奈酚等活性成分可调节TP53、PTGS2等相关靶点。本研究为中医防治慢性肾病提供了依据。
[Metabolomics combined with bioinformatics reveals mechanism of Sanhuang Hushen Fangshuai Decoction in treating chronic kidney disease].
This article aims to analyze the therapeutic effect and probe into the mechanism of Sanhuang Hushen Fangshuai Decoction in treating chronic kidney disease(CKD) based on metabolomics and bioinformatics. The patients with stage 3-4 CKD diagnosed and treated in the Changzhou Hospital of Traditional Chinese Medicine from June 2023 to March 2024 were enrolled in this study. The patients were treated with Sanhuang Hushen Fangshuai Decoction, and the therapeutic effect was evaluated. The serum samples were collected before and after treatment. Ultra-performance liquid chromatography was employed to detect metabolites in the serum, and multivariate statistical analysis was performed. Bioinformatics was employed to screen the active components and targets of the decoction and the potential targets of CKD. The protein-protein interaction(PPI) network of the common targets shared by the decoction and CKD and the drug-component-target network were constructed. The core components and targets were screened according to the correlation degree of the network. The binding between core components and targets was verified by molecular docking. The results showed that Sanhuang Hushen Fangshuai Decoction improved the renal function and reduced proteinuria. Compared with the healthy population, the post-treatment population showed recovery of 54 up-regulated metabolites and 43 down-regulated metabolites. Enrichment analysis results showed that the key pathways included adenosine triphosphate binding cassette(ABC) transport, tryptophan metabolism, and tyrosine metabolism. The results of bioinformatics analysis showed that the core components of Sanhuang Hushen Fangshuai Decoction in treating CKD included kaempferol, β-sitosterol, luteolin, 7-O-methylisolingol, and tanshinone Ⅱ_A. The core targets included TP53, PTGS2, JUN, AKT1, and TNF. Molecular docking results showed that the core components bound well to the target genes. The results of joint pathway analysis suggested that both differential metabolites and key targets were involved in galactose metabolism, nicotinamide metabolism, and other pathways. This study suggests that Sanhuang Hushen Fangshuai Decoction is effective for CKD, and it can regulate multiple abnormal metabolites and participates in multiple metabolic pathways involving amino acids and sugars. The active components such as kaempferol in the decoction may regulate related targets such as TP53 and PTGS2. This study provides a basis for the prevention and treatment of CKD with traditional Chinese medicine.