Anti-Rheumatoid Arthritis Pharmacodynamic Substances Screening of Periploca forrestii Schltr.: Component Analyses In Vitro and In Vivo Combined with Multi-Technical Metabolomics

The purpose of this study was to elucidate the metabolic action patterns ofP. forrestiiagainst rheumatoid arthritis (RA) using metabolomics, and to obtain its potential effective substances for treating RA. First, the therapeutic effects ofP. forrestiiagainst RA were confirmed; second, the chemical composition ofP. forrestiiwas analyzed, and 17 prototypes were absorbed into blood; subsequently, plasma metabolomics studies using UPLC-Triple-TOF-MS/MS and GC-MS were performed to disclose the metabolomics alterations in groups, which revealed 38 altered metabolites after drug intervention. These metabolites were all associated with the arthritis pathophysiology process (−log(p) > 1.6). Among them, sorted by variable important in projection (VIP), the metabolites affected (VIP ≥ 1.72) belonged to lipid metabolites. Finally, Pearson’s analysis between endogenous metabolites and exogenous compounds was conducted to obtain potential pharmacological substances for theP. forrestiitreatment of RA, which showed a high correlation between five blood-absorbed components andP. forrestii-regulated metabolites. This information provides a basis for the selection of metabolic action modes forP. forrestiiclinical application dosage, and potential pharmacological substances that exerted anti-RA effects ofP. forrestiiwere discovered. The study provided an experimental basis for further research on pharmacoequivalence, molecular mechanism validation, and even the development of new dosage forms in the future.Keywords:Periploca forrestiiSchltr.;rheumatoid arthritis;network pharmacology;metabolomics;pharmacodynamic substances