Study on the Effect of Puerarin–Gadolinium on Rheumatoid Arthritis Rats based on Nontargeted Metabolomics Technology

To find potential biomarkers and related metabolic pathways based on metabonomics of rat joint tissue, the rats with stable collagen-induced arthritis (CIA) model were taken as the research object. A rat rheumatoid arthritis model was established by injecting type II collagen. Treatment groups received oral doses of puerarin (40 mg/kg), puerarin-gadolinium (40 mg/kg), gadolinium chloride (40 mg/kg), or methotrexate (0.5 mg/kg), while control groups received saline. After 28 days, joint tissue metabolomics was analyzed using UPLC-MS (Shimadzu LC-30A and SCIEX TripleTOF 6600+), revealing significant metabolite changes and altered metabolic pathways. For the animal experiment part, based on observed changes in morphological, histopathological, and biochemical indicators, puerarin-Gd demonstrated significant therapeutic efficacy, surpassing that of puerarin, gadolinium chloride, and the positive control group. For the metabolomics part, compared with the blank group, the number of significantly different metabolites in the model group was 238, and most of the expressions were upregulated. Compared with the model group, the number of significantly different metabolites in the puerarin-gadolinium treatment group was 165, but most of them were downregulated. The KEGG enrichment pathway showed that the differential metabolites enrichment pathways of the puerarin-gadolinium treatment group and model group were mainly: linoleic acid metabolism, α-linolenic acid metabolism, arachidonic acid metabolism, choline metabolism in cancer, retrograde endogenous cannabinoid signal transduction, and glycerol phosphate metabolism pathway. Puerarin-gadolinium has a good therapeutic effect on rheumatoid arthritis rats, and its mechanism may be related to the inhibition of ferroptosis and the regulation of lipid metabolism.