Abstract
We aimed to explore the active ingredients and molecular mechanism of Tripterygium wilfordii (TW) in the treatment of diabetic nephropathy (DN) through network pharmacology and molecular biology. First, the active ingredients and potential targets of TW were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and related literature materials, and Cytoscape 3.7.2 software was used to construct the active ingredient-target network diagram of TW. Second, the target set of DN was obtained through the disease database, and the potential targets of TW in the treatment of DN were screened through a Venn diagram. A protein interaction network diagram (PPI) was constructed with the help of the String platform and Cytoscape 3.7.2. Third, the ClueGO plug-in tool was used to enrich the GO biological process and the KEGG metabolic pathway. Finally, molecular docking experiments and cell pathway analyses were performed. As a result, a total of 52 active ingredients of TW were screened, and 141 predicted targets and 49 target genes related to DN were identified. The biological process of GO is mediated mainly through the regulation of oxygen metabolism, endothelial cell proliferation, acute inflammation, apoptotic signal transduction pathway, fibroblast proliferation, positive regulation of cyclase activity, adipocyte differentiation and other biological processes. KEGG enrichment analysis showed that the main pathways involved were AGE-RAGE, vascular endothelial growth factor, HIF-1, IL-17, relaxin signalling pathway, TNF, Fc epsilon RI, insulin resistance and other signaling pathways. It can be concluded that TW may treat DN by reducing inflammation, reducing antioxidative stress, regulating immunity, improving vascular disease, reducing insulin resistance, delaying renal fibrosis, repairing podocytes, and reducing cell apoptosis, among others, with multicomponent, multitarget and multisystem characteristics.
Highlights
According to data surveys, it is inferred that by 2030, diabetes will become the seventh most common cause of death in the world (Rao et al, 2019), and diabetic nephropathy (DN) is one of its most serious complications and is the main cause of end-stage renal disease (Liu et al, 2009; Toth-Manikowski and Atta, 2015)
According to the topological parameters, the key compounds of "degree > average value (15.21)" are kaempferol, triptolide, nobiletin, beta-sitosterol, tripterine, stigmasterol, triptoditerpenic acid B, triptinin B, tryptophenolide, 81,827-74-9, triptonoterpene and (2R,3R,4S)-4-(4-hydroxy-3-methoxy-phenyl)-7-methoxy-2,3dimethylol-tetralin-6-ol, a total of 12 species, which may play a key role in Tripterygium wilfordii (TW) treatment of DN
It can be inferred that the treatment of DN by TW may be mainly related to the following biological processes: 1 regulation of oxygen species metabolic process 22.22%; 2 regulation of endothelial cell proliferation 18.52%; 3 acute inflammatory response 11.11%; 4 extrinsic apoptotic signaling pathway in the absence of ligand 3.7%; 5 regulation of fibroblast proliferation 7.41%; 6 positive regulation of cyclase activity 3.7%; 7 regulation of fat cell differentiation 7.41%, etc
Summary
It is inferred that by 2030, diabetes will become the seventh most common cause of death in the world (Rao et al, 2019), and diabetic nephropathy (DN) is one of its most serious complications and is the main cause of end-stage renal disease (Liu et al, 2009; Toth-Manikowski and Atta, 2015). The recommended treatments for DN are to control blood pressure and blood sugar, mainly by administering renin angiotensin aldosterone system (RAAS) inhibitors, sodium glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide 1 (GLP1) receptor agonists. These strategies have shown encouraging results in DN, there are still many diabetic patients who continue to progress towards end-stage kidney disease (ESKD) (Kato and Natarajan, 2019; Barrera-Chimal and Jaisser, 2020). New strategies are needed to supplement existing interventions (Batu Demir and Cooper, 2016)
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