Construction Of Zebrafish Hyperuricemia Model And Screening Of Food And Drugs With Uric Acid-lowering Activity

The incidence of hyperuricemia in China is growing,that affects the health of the population,therefore,the pathogenesis and treatment of hyperuricemia are more important.Edible herbs has the characteristics of high-level safety,wide sources,numerous varieties and few adverse drug reactions.The exploring of edible herbs has become an important part of the research on hyperuricemia therapy.Zebrafish has the potential of being an excellent hyperuricemia model with the advantages in medicine high-throughput screening.Zebrafish can be used as an evaluation platform for screening uric acid-lowering drugs and foods.The development of natural uric acid-lowering drugs can be pushed through building a database of uric acid-lowering functional factors.The goal of this study is constructing a zebrafish hyperuricemia model,screening of food and drugs with uric acid-lowering activity and building an activity evaluation platform.The uric acid-lowering effects of various edible herbs were evaluated.The main method and results of this article are as follows:1.With co-treatment of potassium oxonate and xanthine sodium salt,a zebrafish model of acute hyperuricemia has been constructed for the first time.Allopurinol and anserine were used as positive controls for preliminary validation of the model.Such model could offer a new robust approach for screening of effective and safe food and drugs,the research of hyperuricemia and the exploration of the pathogenesis of gout.2.Through the combination of in vitro（the xanthine oxidase inhibitory activity）and in vivo（a zebrafish hyperuricemia model）methods,the uric acid-lowering activity of twenty edible herbs ethanol crude extracts were screened.In vitro experiments showed that 19 ethanol extracts were inhibitory,with8 having greater than 50%inhibitory rate at 400μm/mL.The most active one was the ethanol extract of the Rhodiola crenulate,which was followed closely by Lagotis brevituba,Poeania suffruticosa,Patrinia scabiosaefolia,Phellodendron chinense,Scindapsus aureus,Cassia tora,and Coreopsis tinctorial.Then uric acid-lowering activity of these 8 extracts were further determined in vivo.The uric acid level of all these eight extract groups were significantly lower than the model group（P<0.05）.Among them,the xanthine oxidase inhibitory activity and the uric acid-lowering effect of the four:Rhodiola crenulate,Patrinia scabiosaefolia,Scindapsus aureus and Coreopsis tinctorial,were reported for the first time.Furthermore,the application of zebrafish hyperuricemia model in practice shows its value in the field of screening uric acid lowering activity drugs and foods.These results provide scientific data and scientific references for further development and utilization of traditional Chinese medicine.3.The HPD-100 macroporous resin was used for preliminary separation of Rhodiola crenulate,and XOD inhibitory activity of each group was verified.XOD inhibitory activity of the 50%ethanol,70%ethanol,and 90%ethanol groups had enhanced compared to the crude ethanol extract,and the IC₅₀ values were all lower.The 30%ethanol component have no XOD inhibitory activity.Among them,XOD inhibitory activity of the 50%ethanol and 70%ethanol components are almost same.The 90%ethanol component has the strongest XOD inhibitory activity.