Mechanism of Wuse Peiyuan Guben Decoction in Treating Chronic Kidney Disease-Protein Energy Wasting: Based on Metabolomics and Network Pharmacology

OBJECTIVE To explore the potential mechanism of Wuse Peiyuan Guben Decoction in treating chronic kidney disease-protein energy wasting(CKD-PEW). METHODS The CKD-PEW model on rats was established by using a 5/6 nephrectomy and low protein diet. Widely targeted metabolomics technology was employed for the serum metabolomics analysis on rats to identify differential metabolites and their corresponding targets, whereas network pharmacology method was utilized to predict the key chemical compositions, targets, and metabolic pathways of Wuse Peiyuan Guben Decoction in treating CKD-PEW. Furthermore, the common targets discovered using the integrated serum metabolomics and network pharmacology analysis were leveraged to construct the component-target-metabolite-pathway network, which presented the main effective chemical compositions and metabolic mechanisms of Wuse Peiyuan Guben Decoction in treating CKD-PEW. RESULTS There were 123 different metabolites between the blank group and the model group, and 50, 37, 62, and 114 different metabolites in the model group compared with the positive control compound α-ketoacid tablets, low, medium, and high dosage Wuse Peiyuan Guben Decoction groups, respectively. There were 25 potential biomarkers enriched in the metabolic pathway between the blank group and the model group by Metabo Analysis, and 2, 2, 5 and 24 potential biomarkers in the model group and the positive control compound α-ketoacid tablets, low, medium and high dosage Wuse Peiyuan Guben Decoction groups, respectively. There were 21 enriched metabolic pathways with 194 targets between the blank group and the model group, and 2 pathways with 14 targets, 2 pathways with 14 targets, 5 pathways with 38 targets, and 24 pathways with 52 targets between the model group and positive control compound α-ketoacid tablets, low, medium and high dose groups, respectively. There were 65 active pharmaceutical ingredients and 123 important targets identified by the network pharmacology analysis. The integrated serum metabolomics and network pharmacology analysis results presented that four common targets: myeloperoxidase, UDP-glucuronosyltransferases, tyrosinase, and paraoxonase-1, were regulated by the four compositions, beta-sitosterol, quercetin, naringenin, salidroside in Wuse Peiyuan Guben Decoction to impact the key biomarkers, 2-hydroxybutanoic acid, hydroquinone, 2-phenylacetamide, and dopaquinone, thereby to affect the metabolic pathways of phenylalanine, propanoate, and tyrosine to finally treat CKD-PEW. CONCLUSION The pathogenesis of CKD-PEW is associated with multiple targets and metabolic pathways, and this study has elaborated on the key effective chemical compositions and metabolic mechanisms of Wuse Peiyuan Guben Decoction in treating CKD-PEW, hopefully providing a solid theoretical and experimental foundation for medical treatment of CKD-PEW.