Urinary metabolomics study on the anti-inflammation effects of flavonoids obtained from Glycyrrhiza

Rheumatoid arthritis (RA) is a chronic disease with pain, swelling, and limitation in the motion and function of multiple joints thus leading to high disability. Previous studies have shown that flavonoids and saponins are the most abundant and active constituents in Glycyrrhiza, which possess a wide range of pharmacological effects such as anti-inflammatory, antioxidant and anti-bacteria. But the mechanisms of those actions are not entirely clear. In order to clarify the mechanisms of those actions, the pharmacodynamical assessments of extraction of water-soluble components and flavonoids and saponins obtained from Glycyrrhiza were investigated. Combining the pharmacodynamical researches, we found that flavonoids obtained from Glycyrrhiza had more significant therapeutic effects on acute inflammation, chronic inflammation and inflammatory pain than that of extraction of water-soluble components and saponins obtained from Glycyrrhiza. The results indicated that flavonoids are the main medicinal ingredients in Glycyrrhiza. In order to further investigate the mechanism of the action of flavonoids in Glycyrrhiza on treating RA, a urine metabolomics method based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was established to observe the metabolic variations in adjuvant-induced arthritis (AIA) rats and investigate the therapeutic effect of flavonoids in Glycyrrhiza on RA. As a result, twenty potential biomarkers were found by comparison with the model group (MG) and flavonoid treated group (FG). We associated these compounds with related metabolic pathways, the results showed that these biomarkers were mainly associated with purine metabolism, taurine and hypotaurine metabolism, tryptophan metabolism, phenylalanine metabolism, tricarboxylic acid cycle (TCA cycle), pantothenate and coenzyme A (CoA) biosynthesis. The results about the pharmacodynamics and metabolomics provided a theoretical basis for clarifying the mechanism of flavonoids in Glycyrrhiza in the treatment of RA.