Metabolomics analysis of the therapeutic effects of Qiwei Tongbi oral liquid on rheumatoid arthritis in rats.

Qiwei Tongbi oral liquid (QWTB), a classical traditional Chinese medicine (TCM) formula, has a good therapeutic effect on rheumatoid arthritis (RA) and is widely used in China. To comprehensively elucidate the therapeutic mechanism of QWTB in the treatment of RA, the effects of QWTB on biomarkers and metabolic pathways in a rat model of kidney deficiency arthritis were investigated in this study. The effects of QWTB on pharmacodynamic indicators, including paw swelling, arthritis score; interleukin-1ß, interleukin-6, interleukin-17 F, tumor necrosis factor-α, tartrate-resistant acid phosphatase 5b, bone alkaline phosphatase, bone-specific alkaline phosphatase, bone glaprotein, urea, and creatinine levels; and histopathology, suggested that QWTB significantly improved renal function, inhibited the inflammatory response, and reduced bone loss. In total, 39 differential metabolites were screened by comparing the endogenous components between blank and model rat plasma, among which 16 metabolites were altered by QWTB. The metabolism pathway analysis revealed that α-linolenic acid metabolism, phenylalanine metabolism, sphingolipid metabolism, histidine metabolism and glycerophospholipid metabolism were greatly disturbed. Thus, the biomarkers investigated included (1) α-linolenic acid, (2) hippuric acid, (3) phosphatidylethanolamine (15:0/22:2(13Z,16Z)), (4) phenylpyruvic acid, (5) sphinganine, and (6) urocanic acid. QWTB affected three abnormal biomarkers: (3), (4), and (6). Phenylphruvic acid, sphinganine and urocanic acid were significantly associated with pharmacodynamic indicators, as shown by Pearson correlation analysis. These results indicated that RA-related biomarkers had certain reliability and biological significance. In summary, QWTB regulated the metabolic disorders in rats with RA. Its therapeutic mechanism may involve the regulation of phenylalanine metabolism, histidine metabolism, and glycerophospholipid metabolism. The results of this study are useful for understanding the therapeutic mechanisms of TCM.