| Summary: | <i>Aconitum carmichaeli</i> with <i>Ampelopsis japonica</i> (AA) is a classical traditional Chinese medicine (TCM) formula. There are a lot of examples showing that AA can be used to treat rheumatoid arthritis, but its mechanism of action is still not completely clear. In this research, collagen-induced arthritis (CIA) was chosen as a rheumatoid arthritis (RA) model. Rats of treated groups were continuously administered <i>Aconitum carmichaeli</i> (AC), <i>Ampelopsis japonica</i> (AJ) and <i>Aconitum carmichaeli</i> + <i>Ampelopsis japonica</i> (AA) orally once a day from the day after the onset of arthritis (day 7) until day 42. The results showed that AA not only significantly reduced paw swelling, but also improved the levels of TNF-α and IL-6 in serum. GC-MS-based urine metabonomics was established to analysis metabolic profiles and 21 biomarkers of RA rats were identified by the Partial Least Squares Discriminant Analysis (PLS-DA) and Support Vector Machine (SVM) methods. The prediction rate of the SVM method for the 21 biomarkers was 100%. Twenty of 21 biomarkers, including D-galactose, inositol and glycerol, gradually returned to normal levels after administration of AA. Metabolomic Pathway Analysis (MetPA) generated three related metabolic pathways—galactose metabolism, glycerolipid metabolism and inositol phosphate metabolism—which explain the mechanism of AA treatment of rheumatoid arthritis. This research provides a better understanding of the therapeutic effects and possible therapeutic mechanism of action of a complex TCM (AA) on rheumatoid arthritis.
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