Protective effects of Typhonii Rhizoma in rheumatoid arthritis rats revealed by integrated metabolomics and network pharmacology

Rheumatoid arthritis (RA) is an autoimmune disease with a 0.5% prevalence worldwide. Inflammation, periosteal proliferation and joint destruction are the main clinical symptoms of RA. Typhonii Rhizoma (TR) is the dry tuber of the Araceae plant Typhonium giganteum Engl, and possesses many uses such as dispelling obstructive wind-phlegm and relieving pain. It is used for the clinical treatment of arthromyodynia and RA. However, the mechanism of action remains unclear. In this study, we first evaluated the effects of TR in type II collagen-induced RA model rats. Secondly, in serum metabolomics, TR could ameliorate 11 potential metabolites in RA model rats and reversed RA through pentose and glucuronate interconversions, sphingolipid metabolism, glycerophospholipid metabolism and tryptophan metabolism. To further explore the mechanisms of TR, 40 chemical constituents were used to establish a component-target interaction network. Some key genes were verified by in vitro pharmacological tests by integrating the results from the network pharmacology and metabolomics. The verification results showed that the mechanisms of TR against RA may be related to the inhibition of the production of inflammatory cytokines and the expression and function of HIF1-alpha. This study serves as a theoretical basis for the treatment of RA with TR.