Investigation of the Mechanism of Periploca forrestii against Rheumatoid Arthritis with Network Pharmacology-Based Analysis

Periploca forrestii Schltr (P. forrestii) is an edible medicinal herb with various health benefits such as treating antirheumatoid arthritis (RA), reducing inflammation, and preventing tumor growth. The active ingredients in P. forrestii responsible for its protective effect against RA, however, remain unknown. In this study, the active ingredient of P. forrestii and its potential mechanism of action against RA were investigated by network pharmacology and enrichment analysis. The methods included predicting target genes of P. forrestii, constructing a protein interaction network, and performing gene-ontology (GO) and Kyoto-encyclopedia of genes and genomes (KEGG) enrichment analysis. We discovered targets of RA through retrieval of OMIM and GeneCards public databases. Cardiac glycosides (CGs) are considered the primarily active ingredients of P. forrestii, and the target genes of GCs were discovered to be overlapped with relevant targets of RA using the Venn diagram. After that, prediction of relevant targets of P. forrestii was accomplished with a network pharmacology-based approach. Through the Venn diagram, we discovered 99 genes shared in the target genes of P. forrestii and RA. Gene enrichment analysis showed that the mechanisms of CGs against RA are associated with 55 signaling pathways, including endocrine resistance, Epstein-Barr virus infection, bladder cancer, prostate cancer, and coronavirus disease (COVID-19) signaling pathways. Coexpression analysis indicated ADSL, ATIC, AR, CCND1, MDM2, and HSP90AA1 as the hub genes between putative targets of P. forrestii-derived CGs and known therapeutic targets of RA. In conclusion, we clarified the mechanism of action of P. forrestii against RA, which would provide a basis for further understanding the clinical application of P. forrestii.