| Rheumatoid arthritis (RA) is a common human autoimmune disease characterized by chronic and concomitant destruction of cartilage and bone. It is the most common form of inflammatory arthritis, and has a substantial societal effect in terms of cost, disability, and lost productivity. The current treatment goal in RA is to achieve persistent, total disease suppression resulting in remission. Most treatments for RA are directly to normalize the immune system and to reduce inflammatory mediators. Therapeutic agents, such as disease modifying anti-rheumatic drugs (DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs) and hormone drugs are clinically common. The validity of long-term treatment with these medicines has not yet been proven. Challenges still unresolved include the issues in disease prevention, approaches to facilitate tissue repair, and treatment optimization to fit the individual patient’s disease phenotype and comorbidity context.Traditional Chinese Medicine (TCM), a unique medical system with the significant characteristic of the use of multicomponent drugs, can hit multiple targets with multiple components. the form of combination drug formulas in an attempt to improve therapeutic efficacy and reduce drug-related side effects and may also be an effective way of decreasing drug resistance. Despite the great progress in the isolation and identification of many compounds from botanicals or TCM herbs, there is still a bottleneck in the development of methodology to characterize the holistic efficacy and synergism of multicomponent drugs, especially for the formulas of TCM. The emergence of metabonomics, which can impact the global metabolic state of entire organism, may also provide a new vision of assessment of the holistic efficacy 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, we applied the metabonomic method to investigate the biochemical abnormalities in collagen-induced arthritis rats and assess the therapeutic effects of HLJDD and its compounds. The findings of metabolic pathways and potential biomarkers related to collagen-induced arthritis will be helpful to dissect the underlying efficacies and mechanisms of TCM. CIA rats were treated daily with oral administration of different doses of HLJDD (135,270.540mg/kg),13main components combination (20.26,40.52,81.03mg/kg), berberine (6.48,12.96.25.92mg/kg), baicalin (5.28,10.56,21.12mg/kg), Dexamethasone (0.05mg/kg) beginning on the day on the day after the onset of arthritis(day12, the therapeutic treatment) until day31. Plasma and urine samples for metabolomic study were collected on18,25,31day during the animal experiment. By combining with partial least squares discriminant analysis (PLS-DA),37biomarkers (17in plasma,24in urine and4in both of them) were identified and primarily involved six metabolism pathways, such as tricarboxylic acids cycle metabolism, lipid metabolism, tryptophan metabolism, phenylalanine metabolism, purine metabolism and pyrimidine metabolism. It is demonstratd that energy metabolism, tryptophan metabolism phenylalanine and oxidative injury are the most related pathological changes in CIA.The regulated biomarkers are mainly related to the energy metabolism, phenylalanine metabolism pathways. HLJDD could definitely inhibit the CIA development and reverse some pathological biomarkers including Citric acid, Succinic acid, Pantothenic Acid, Uridine, D-proline, L-phenylalanine to normal level, it revealed that HLJDT could reverse the pathological process of RA through partly regulating the disturbed energy metabolism, phenylalanine metabolism pathways and oxidative stress. |
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