Abstract: Objective To explore the efficacy and safety of the combination of chicory extract and febuxostat in treating hyperuricemia in rats, and to give tips about related pharmacovigilance. Methods SD rats were randomly divided into ten groups including the control group, HUA model group, low and high-dose febuxostat groups (0.9 mg·kg^-1 and 1.8 mg·kg^-1), low and high-dose chicory extract groups (2.5 g·kg^-1 and 5 g·kg^-1), low-dose febuxostat+low-dose chicory extract group, low-dose febuxostat + high-dose chicory extract group, high-dose febuxostat + low-dose chicory extract group, and the high-dose febuxostat + high-dose chicory extract group. A hyperuricemia rat model was established via 28 consecutive days of intragastric administration of potassium oxonate (750 mg·kg^-1) and yeast extract (10 g·kg^-1). The levels of serum uric acid (SUA) in each group were dynamically monitored. After the experiment, the serum levels of xanthine oxidase (XOD), related indicators and histopathological conditions of the heart, liver, and kidneys were detected to evaluate the safety of the combination. Considerations for the combined use of chicory extract and febuxostat in reducing uric acid were outlined. Results At each stage of the experiment, the SUA levels of rats in the four combination groups under the hyperuricemia state were significantly reduced. Levels of uric acid were lowered more significantly in each combination group than that in the single-agent groups at the corresponding dose, and more markedly in the febuxostat high-dose + chicory high-dose group at 28 d than in the febuxostat high-dose group and chicory high-dose group (P<0.05). The safety indexes of the heart, liver and kidney and results of histopathological staining pointed to no significant changes in the four combination groups compared with the control group, suggesting that the combination could be safely used for lowering uric acid. The indexes of the heart and kidney injury were more significantly improved in the combination group than in the febuxostat single-dose group (especially the high dose). In addition, the combination of chicory extract with febuxostat in the low-dose group had a better safety profile than the combination in the high-dose group. Conclusion The combination of chicory extract and febuxostat can significantly reduce serum levels of uric acid, with better efficacy and safety than single use. The overall effect is the best in the low-dose febuxostat combined with chicory extract group. It is recommended that clinicians start with the minimum dose, regularly monitor serum uric acid levels and organ functions, and be wary of drug interactions.

Key words: Chicory Extract, Febuxostat, Combination of Traditional Chinese and Western Medicine, Lowering of Uric Acid, Hyperuricemia(HUA), Pharmacovigilance, Rat