Background TongFengTangSan (TFTS) is a commonly used Tibetan prescription for gout treatment. Previously, TFTS (CF) was confirmed to have a significant uric acid-lowering effect. However, the anti-hyperuricemia mechanisms and the main active fractions remain unclear. The current study aimed to investigate the anti-hyperuricemia mechanism using metabolomics and confirm the active CF fraction. Methods The hyperuricemia model was established through intraperitoneal injection containing 100 mg/kg potassium oxonate and 150 mg/kg hypoxanthine by gavage. We used serum uric acid (sUA), creatinine (CRE), blood urea nitrogen (BUN), xanthine oxidase (XOD) activity, interleukin-6 (IL-6) and interleukin-1β (IL-1β) as indicators to evaluate the efficacy of CF and the four fractions (SX, CF30, CF60, and CF90). The anti-hyperuricemia mechanism of CF was considered through non-targeted metabolomics depending on the UPLC-Q-TOF–MS technology. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) helped explore the potential biomarkers in hyperuricemia. Moreover, the differential metabolites and metabolic pathways regulated by CF and four fractions were also assessed. Results CF revealed a significant anti-hyperuricemia effect by down-regulating the level of sUA, sCRE, sIL-1β, and XOD. SX, CF30, CF60, and CF90 differed in the anti-hyperuricemia effect. Only CF60 significantly lowered the sUA level among the four fractions, and it could be the main efficacy fraction of TFTS. Forty-three differential metabolites were identified in hyperuricemia rats from plasma and kidney. Pathway analysis demonstrated that seven pathways were disrupted among hyperuricemia rats. CF reversed 19 metabolites in hyperuricemia rats and exerted an anti-hyperuricemia effect by regulating purine metabolism. CF60 was the main active fraction of TFTS and exerted a similar effect of CF by regulating purine metabolism. Conclusions CF and CF60 could exert an anti-hyperuricemia effect by regulating the abnormal purine metabolism because of hyperuricemia while improving intestinal and renal function. CF60 could be the main active fraction of TFTS.

Background: TongFengTangSan (TFTS) is a commonly used Tibetan prescription for the treatment of gout. Previously, we confirmed that 90% alcohol extract of TFTS (CF) has a significant uric acid-lowering effect; however, the anti-hyperuricemia mechanisms and main active fractions remain unclear. This study aimed to investigate the anti-hyperuricemia mechanism by metabolomics and confirm the active fraction of CF. Methods: Hyperuricemia model was established by intraperitoneal injection of 100 mg/kg potassium oxonate and 150 mg/kg hypoxanthine by gavage. The serum uric acid (sUA), creatinine (CRE), blood urea nitrogen (BUN), xanthine oxidation (XOD) activity, interleukin-6 (IL-6) and interleukin-1β (IL-1β) were used as indicators to evaluate the efficacy of the CF and four fractions (SX, CF30, CF60, and CF90). The anti-hyperuricemia mechanism of CF in the treatment of hyperuricemia was evaluated through nontargeted metabolomics based on UPLC-Q-TOF-MS technology. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to explore the potential biomarkers in hyperuricemia, as well as the differential metabolites and metabolic pathways regulated by CF and four fractions.Results: CF showed the significant anti-hyperuricemia effect through the down-regulation on the level of sUA, sCRE, sIL-1β and XOD. SX, CF30, CF60, and CF90 showed the difference on the anti-hyperuricemia effect. Among four fractions, CF60 significantly lowered the level of sUA and could be the main lowering uric acid efficacy fraction of TFTS. 33 differential metabolites were identified in hyperuricemia rats. Pathway analysis revealed five pathways disrupted in hyperuricemia rats. CF reversed 12 endogenous metabolites and the anti-hyperuricemia mechanism of CF could involve in the regulation on purine metabolism and riboflavin metabolism. SX, CF30, CF60, and CF90 regulated 6, 6, 10 and 5 differential metabolites, and involved in differential metabolic pathways, respectively. Among these metabolic pathways, CF60 regulate purine metabolism and riboflavin metabolism. In addition, CF and CF60 could improve intestinal and renal function through the reverse of abnormality of purine metabolism. Conclusions: CF60 could be the main active fraction of CF. CF and CF60 could exert anti-hyperuricemia effect through the regulation on the abnormal purine metabolism caused by hyperuricemia and consequently the improvement of intestinal and renal function.