Wuji Pills (戊己丸) Treats Metabolic Inflammation:a Study Based on Network Pharmacology and Animal Experiment
Objective:To explore the mechanism of Wuji Pills (戊己丸) in treating metabolic inflammation by network pharmacology and animal experiments.Methods:The chemical constituents and targets of Huanglian (黄连) and Wuzhuyu (吴茱萸) in Wuji Pills was retrieved from the Traditional Chinese Medicine Pharmacology Systems Database and Analysis Platform (TCMSP).The genes corresponding to the targets were obtained from GeneCards,Online Mendelian Inheritance in Man (OMIM).Cytoscape 3.7.2 was employed to establish the compound-target network of Wuji Pills,and STRING to establish the protein-protein interaction (PPI) network.Bioconductor was used for the gene on-tology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the targets.Animal experiments were carried out to study the changes in the expression levels of the proteins involved in the predicted pathways associated with the treatment of metabolic inflammation by Wuji Pills.Results:The main active constituents of Wuji Pills included quercetin,isorhamnetin,phytosterol,hydroberberine,and berberine,which corresponded to the targets such as IL6,CASP3,VEGFA,EGFR,and MYC.The GO annotation predic-ted the biological processes such as fatty acid metabolism and cell apoptosis,the cell components such as extracellular matrix and sarcoplasmic reticulum,and the molecular functions such as redox.The key targets were mainly enriched in PI3K-Akt,MAPK,IL-17,NF-kB,FOXO,and AMPK signaling pathways.The results of animal experiments showed that compared with the model group,Wuij Pills (3 g/kg) lowered the total cholesterol,reduced the inflammatory lesions of the liver tissue,up-regulated the protein levels of p-PI3K,p-AKT,and p-eNOS,down-reg-ulated the mRNA levels of Il6,Il18 and Tnfα,and up-regulated the mRNA level of Il10 (P<0.05 or P<0.01).Conclusion:The active com-pounds in Wuji Pills can treat metabolic inflammation by improving cell apoptosis and redox reaction and regulating inflammatory cytokines.