Non-target metabonomic method provided new insights on the therapeutical mechanism of Gancao Fuzi decoction on rheumatoid arthritis rats

Gancao Fuzi decoction (GFD) is a classic Chinese medicine formula for the treatment of rheumatic and rheumatoid arthritis. The main active components of GFD are alkaloids, flavonoids and saponins. This study aimed to clarify the pharmacodynamic effects of the active components in GFD and investigate the mechanism of them treating rheumatoid arthritis rats by the method of metabonomics. Seven groups were studied, named as the normal group (NG), the model group (MG), the Gancao Fuzi decoction treatment group (GFDe), the alkaloids group (ALK), the compatibility of alkaloids with flavonoids group (AF), the compatibility of alkaloids with saponins group (AS) and the compatibility of alkaloids with flavonoids and saponins group (AFS), respectively. Firstly, the anti-inflammatory and analgesic effects of these groups were studied. Besides, urinary metabonomics based on ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLCQ-TOF-MS) was employed for delineation of metabolic alterations in the rats. Based on our results, it is concluded that AFS showed better anti-inflammatory and analgesic activities in GFD. Urinary metabonomic study and multivariate statistical analyses were used to investigate the mechanism of different groups. 26 potential biomarkers have been identified. By the analysis of heat map combined with score plot, the AFS group was the closest group to the NG group after treatment in GFD. The changes of urinary endogenous metabolites showed that AFS exhibited better effect on regulating the taurine and hypotaurine metabolism, phenylalanine metabolism, TCA cycle, tryptophan metabolism, fatty acid metabolism, vitamin B6 metabolism, arginine and proline metabolism and purine metabolism pathways. The pharmacodynamics results showed that three components of flavonoids, saponins and alkaloids in GFD played an overall efficacy. Metabonomics studies showed that the compatibility of three components in GFD achieved the therapeutic effect by regulating the perturbations of multiple metabolic pathways.