Abstract
Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. Owing to its complicated pathogenesis, no satisfactory treatment strategies for DN are available. Milkvetch Root is a common traditional Chinese medicine (TCM) and has been extensively used to treat DN in clinical practice in China for many years. However, due to the complexity of botanical ingredients, the exact pharmacological mechanism of Milkvetch Root in treating DN has not been completely elucidated. The aim of this study was to explore the active components and potential mechanism of Milkvetch Root by using a systems pharmacology approach. First, the components and targets of Milkvetch Root were analyzed by using the Traditional Chinese Medicine Systems Pharmacology database. We found the common targets of Milkvetch Root and DN constructed a protein-protein interaction (PPI) network using STRING and screened the key targets via topological analysis. Enrichment of Gene Ontology (GO) pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. Subsequently, major hubs were identified and imported to the Database for Annotation, Visualization and Integrated Discovery for pathway enrichment analysis. The binding activity and targets of the active components of Milkvetch Root were verified by using the molecular docking software SYBYL. Finally, we found 20 active components in Milkvetch Root. Moreover, the enrichment analysis of GO and KEGG pathways suggested that AGE-RAGE signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway might be the key pathways for the treatment of DN; more importantly, 10 putative targets of Milkvetch Root (AKT1, VEGFA, IL-6, PPARG, CCL2, NOS3, SERPINE1, CRP, ICAM1, and SLC2A) were identified to be of great significance in regulating these biological processes and pathways. This study provides an important scientific basis for further elucidating the mechanism of Milkvetch Root in treating DN.
Highlights
According to an epidemiological survey, the number of Chinese adults of ages over 18 who suffered from diabetes mellitus (DM) was 10.4% in 2013, ranking the first in the world [1]
Screening of Active Ingredients. e active components of Milkvetch Root were retrieved from the TCMSP database, and 87 related components were obtained. 20 related components were identified to have oral bioavailability (OB) ≥ 30% and DL ≥ 0.18
The 6 violet nodes represent the active ingredients of Milkvetch Root; the 16 blue nodes represent the overlapping gene symbols between the disease and drug. e edges denote that the nodes can interact with each other. e network shows that the drug may indirectly regulate diseaserelated proteins while Milkvetch Root can directly affect these proteins. ere were 16 overlaps among 393 disease gene symbols and 180 drug gene symbols (Figure 5)
Summary
According to an epidemiological survey, the number of Chinese adults of ages over 18 who suffered from diabetes mellitus (DM) was 10.4% in 2013, ranking the first in the world [1]. Diabetic nephropathy (DN) is one of the most common complications of DM [2]. DN is the most common cause of end-stage renal disease (ESRD) in many parts of the world, including Europe, Japan, and the United States, wherein diabetic patients accounted for. 25% to 45% of all patients enrolled in end-stage renal disease programs [3]. E early onset of DN is insidious and difficult to detect early. Once DN has reached the end of its clinical development, it is difficult to reverse. The treatment of diabetic nephropathy mainly includes strict control of blood glucose, blood pressure, and antidiabetic drugs, which all can only delay the progress of renal damage, as there are no new therapies that can directly
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