| Rheumatoid arthritis (RA) is one kind of autoimmune diseases characterized by persistent synovitis, systemic inflammation and autoantibodies. RA primarily affects the small diarthrodial joints of the hands and feet, causes swelling and pain and, if untreated, may result in deformity. Current medications in the treatment of rheumatoid arthritis, including non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids and biological agents, are limited by a number of well-characterized clinical side-effects, such as hepatotoxicity, blood dyscrasias, gastrointestinal and cardiac toxic effects. Therefore, the exploration of new anti-RA drugs with high efficacy and less toxicity are eagerly needed. Traditional Chinese medicine (TCM), a unique medical system with the significant characteristic of the use of multi-component drugs, can hit multiple targets with its components, improve therapeutic efficacy, reduce drug-related side effects and may also be an effective way of decreasing drug resistance. The study of TCM has aroused much interest recently due to its superiority in the treatment of complex multi-factor diseases, such as RA. However, the holistic efficacy and synergism of TCM characterization is a bottleneck and its mechanism remains to be elucidated. Metabolomics, which provides insights into the global metabolic state of integrated living systems and dynamic responses to the changes of both endogenous and exogenous factors, has many potential applications and advantages for the research of complex systems and may also provide a new vision of assessment of the integrity and systemic feature of TCM.Huang-Lian-Jie-Du decoction (HLJDD), a classic formula to clear "heat" and "poison", is an aqueous extract of four herbal materials, Rhizoma coptidis, Radix scutellariae, Cortex phellodendri and Fructus gardeniae. In the present study, a rapid-resolution liquid chromatography tandem quadrupole time-of-flight mass spectrometry (RRLC-Q/TOF-MS) based metabolomic study was developed to obtain a systematic view of the progression of RA and assess the efficacy of HLJDD and its compounds in collagen-induced arthritis rats. Forty male Wistar rats were randomly divided into five groups, including normal control group, model group, dexamethasone group, HLJDD group and the mixture of13components of HLJDD group after immunized with bovine type â…¡ collagen. Plasma and urine samples for metabolomic study were collected on8,15,22day during the animal experiment. By combining with partial least squares discriminant analysis,48potential biomarkers were identified, including27in plasma,24in urine and3in both of them, and primarily involved in amino acids, purine, pyrimidine and unsaturated fatty acids metabolisms, which revealed a new insight into the RA network in vivo. It can be seen that RA is a complex disease caused by amino acids, nucleic acids and lipids metabolisms. Metabolites concerned with oxidative action (carnitine, acetylcarnitine, uric acid and allantoin) appear to have diagnostic or prognostic values for RA, which deserve to be further investigated. Taking the potential biomarkers found in the study as screening indexes, it revealed that HLJDD and its compounds could reverse the pathological process of RA through partly regulating phenylalanine, tryptophan and unsaturated fatty acids metabolisms and inhibiting oxidative stress reaction. The finding of metabolic pathways and potential biomarkers related to RA will be helpful to dissect the underlying efficacies and mechanisms of HLJDD in treating RA. |
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