Molecular mechanism of Xiaohuoluo wan for rheumatoid arthritis by integrating in vitro and in vivo chemomics and network pharmacology

Abstract The cause of rheumatoid arthritis (RA) is unclear. Xiaohuoluo wan (XHLW) is a classical Chinese medicine that is particularly effective in the treatment of RA. Given the chemical composition of XHLW at the overall level has been little studied and the molecular mechanism for the treatment of RA is not clear, we searched for the potential active compounds of XHLW and explored their anti‐inflammatory mechanism in the treatment of RA by flexibly integrating the high‐resolution ultra‐performance liquid chromatography–mass spectrometry (UPLC–MS)‐based in vitro and in vivo chemomics, network pharmacology, and other means. The results of the study identified that the active compounds of XHLW, such as alkaloids, nucleosides, and fatty acids, may play an anti‐inflammatory role by regulating key targets such as IL‐2, STAT1, JAK3, and MAPK8, inducing immune response through IL‐17 signaling pathway, T‐cell receptor, FoxO, tumor necrosis factor (TNF), and so forth, inhibiting the release of inflammatory factors and resisting oxidative stress and other pathways to treat RA. The results of this study provide referable data for the screening of active compounds and the exploration of molecular mechanisms of XHLW in the treatment of RA.