High-throughput metabolomics exploring the pharmacological effect and mechanism of icariin on rheumatoid arthritis rat based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry

Peng Zhou ^* Yushi TIAN Qianqian Liu Shouze Ren Hua Liang

• Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China

Metabolomics could provide an insight into the pharmacological effect and mechanism via assessing relevant biomarkers and biological pathways changes. Icariin (ICA) is a promising flavonoid compound with significant anti-cancer activity, however, the pharmacological mechanism of ICA in the treatment of rheumatoid arthritis (RA) needs to be further explored. The metabolic profile changes of serum samples were revealed using non-targeted metabolomics based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Tissue histopathology, physical parameter as well as biochemical indicators analysis were also measured in revealing the mechanism of ICA in the treatment of RA. Thirty-one potential biomarkers were identified to highlight the metabolic disorders in RA animals model, of which twenty-three of them were regulated by ICA treatment mainly involved in alanine, aspartate and glutamate metabolism, arachidonic acid metabolism, citrate cycle, pyruvate metabolism as well as glycolysis/gluconeogenesis pathways. The anti-cancer mechanism of ICA on RA may be mediated by ameliorating amino acid metabolism, unsaturated fatty acid metabolism, citrate cycle, pyruvate metabolism and others, regulating the oxidative stress state and inflammatory effects. Metabolomics approach is a promising tool for revealing the disturbed biomarkers and pathways of RA to dissect effects and mechanism of ICA, which benefits the natural medicines development.