Mechanism study of Sanmiao Pill in the treatment of rheumatoid arthritis based on serum metabolomics technology

Objective To study the anti-rheumatoid arthritis mechanism of Sanmiao Pill by using liquid chromatography-mass spectrometry. Methods The rats were randomly divided into control group, model group and medicated group based on weight, 8 rats in each group. The model group and medicated group were treated by intradermal injection of 0.1 ml complete Freund's adjuvant on buttock(s). Rats of medicated group were given Sanmiao Pill solution 0.054 g/ml by gavage, 1 ml/100 g based on weight from the 7th day of experiment for 7 days. And then to score the degree of feet swelling of rats. After 48 hours of the last medication, to collecte the blood samples for metabolic fingerprint analysis. Then analized and processed the non-targeted contour mass spectrometry data (Continuum model) with unsupervised principal component method; identified the maximum metabolic differences between rheumatoid arthritis rats and healthy rats by dimension reduction technic. The differential ions were screened and locked by supervised pattern recognition analysis. Finally, with the help of the automated analysis software database like HMDB, identifiedthe structures and analized the correlated metabolic pathway. Results Compared with the model group, the swelling degree of the feet (2.01 ± 0.19 ml vs. 2.27 ± 0.30 ml) in medicated group significantly decreased (P<0.01). The HMDB data shows that the metabolic profiles of rats were mainly distributed in the control group and the model group, which proved that the rheumatoid arthritis rats treated with Sanmiao Pill had a pullback trend, and the overall metabolic level has a healthy state. With this analysis, 20 blood biomarkers related to rheumatoid arthritis were obtained, which involved the metabolic pathways of aminoacyl-tRNA biosynthesis, Glycine, Serine and Threonine metabolism, Alanine, Aspartic acid and Glutamic acid metabolism, Linoleic acid metabolism, Arachidonic acid metabolism. Conclusions Sanmiao Pill has interventional effect on rheumatoid arthritis rats. The mechanism might be related with metabolic enzymes and metabolic pathways such as Alanine, Aspartic acid and Glutamic acid. Key words: San Miao Pill; Arthritis, rheumatoid; Metabolomics; Biomarkers; Metabolic Pathway; Inflammation; Rats