ABSTRACT
Background: IgA nephropathy (IgAN) is a major and growing public health problem. Renal fibrosis plays a vital role in the progression of IgAN. This study is to investigate the mechanisms of action underlying the therapeutic effects of Shenbing Decoction II (SBDII) in IgAN renal fibrosis treatment based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology and experimental verification. Method: We first used UPLC-MS/MS to explore the main compounds of SBDII, and then used network pharmacology to predict the targets and key pathways of SBDII in the treatment of IgAN renal fibrosis. Next, bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were used to induce IgAN in rats, and then biochemical indicators, renal tissue pathology, and renal fibrosis-related indicators were examined. At the same time, part of the results predicted by network pharmacology were also verified. Result: A total of 105 compounds were identified in SBDII by UPLC-MS/MS. Network pharmacology results showed that the active compounds such as acacetin, eupatilin, and galangin may mediate the therapeutic effects of SBDII in treating IgAN by targeting tumor protein p53 (TP53) and regulating phosphatidylinositol 3-kinase (PI3K)-Akt kinase (Akt) signaling pathway. Animal experiments showed that SBDII not only significantly improved renal function and fibrosis in IgAN rats, but also significantly downregulated the expressions of p53, p-PI3K and p-Akt. Conclusion: This UPLC-MS/MS, network pharmacological and experimental study highlights that the TP53 as a target, and PI3K-Akt signaling pathway are the potential mechanism by which SBDII is involved in IgAN renal fibrosis treatment. Acacetin, eupatilin, and galangin are probable active compounds in SBDII, these results might provide valuable guidance for further studies of IgAN renal fibrosis treatment.
ABSTRACT
OBJECTIVE: To identify the main active components in Shenbing decoction â ¢ and their targets and explore the mechanism by which Shenbing decoction â ¢ alleviates proteinuria in chronic kidney disease (CKD) based on network pharmacology. METHODS: The active components of Shenbing decoction â ¢ and their potential targets, along with the oral bioavailability and drug-like properties of each component were searched in the TCMSP database. The proteinuria-related targets were searched in the GeneCards database. The active component-target network was constructed using Cytoscape software, and the acquired information of the targets from ClueGO was used for enrichment analysis of the gene pathways. RESULTS: A total of 102 active components were identified from Shenbing decoction â ¢. These active components acted on 126 targets, among which 69 were related to proteinuria. Enrichment analysis revealed fluid shear stress- and atherosclerosisrelated pathways as the highly significant pathways in proteinuria associated with CKD. CONCLUSIONS: We preliminarily validated the prescription of Shenbing decoction â ¢ and obtained scientific evidence that supported its use for treatment of proteinuria in CKD. The findings in this study provide a theoretical basis for further study of the mechanism of Shenbing decoction â ¢ in the treatment of proteinuria in CKD.