Yiren-mugua Huazhuo Decoction Decreases The Uric Acid In Hyperuricemia Mice

Background:Hyperuricemia(HUA)is a group of diseases that cause decreased uric acid excretion and / or impaired purine metabolism in the body due to heredity and acquisition.The incidence of hyperuricemia is increasing year by year,and the incidence is higher in men than in women.A large number of studies have proven that hyperuricemia not only causes diseases such as gout,but also is closely related to the occurrence and development of diseases such as hypertension,diabetes,cardiovascular disease,and kidney disease.Our previous research found that Coixen Jiangzhuo Decoction can inhibit the swelling of rats' feet caused by urate,reduce the serum uric acid concentration,improve the pathological changes of the synovial tissue of the ankle joints,and have a significant effect on acute gouty arthritis in rats..We found that Jiangciling can significantly reduce the serum uric acid level in rats with hyperuricemia,and can reduce the levels of urea nitrogen and serum creatinine.It has a slowing effect on kidney injury,and its underlying mechanism has not been clearly defined.In order to further research and develop uric acid-lowering drugs,according to Professor Hu Xuguang's many years of clinical experience,based on ancient recipes,the Coix-Ren Jiangzhuo Decoction and Jiangciling were obtained to obtain Coix-Ren Papaya Huazhuo Decoction.Coix seed papaya Huazhuo decoction has obvious uric acid lowering effect in clinical application,but its possible mechanism has not been clarified yet.This experiment uses potassium oxazinate combined with hypoxanthine to replicate a mouse model of hyperuricemia,and studies the effect and mechanism of Coix Seed Papaya Huazhuo Decoction on uric acid in model mice.Objective:This topic is to study the effect and mechanism of uric acid decoction of Coix Papaya Huazhuo Decoction from three perspectives: in vivo pharmacology experiment,in vitro enzyme experiment,and in vitro cell model experiment.The development research of the soup provides a theoretical basis.Methods:1.There were 66 male Kunming mice.After three days of adaptive feeding,11 were left as the blank group.The other 55 mice were administrated with potassium oxazinate combined with hypoxanthine to replicate the hyperuricemia model in mice.The allopurinol group,the model group,the Coix Papaya Huazhuo Decoction high-dose group,the Coix Papaya Huazhuo Decoction medium-dose group,and the Coix Papaya Huazhuo Decoction low-dose group 5 groups were given 4 weeks of intragastric intervention.After the experiment,the mice were weighed,blood was anesthetized,and the mice were sacrificed by cervical dislocation.The mice's internal organs were dissected out,and the internal organs were weighed and divided.Serum and part of the liver were taken for biochemical kit detection,and serum uric acid(HUA),creatinine(Cr),serum urea nitrogen(BUN),xanthine oxidase(XOD)levels,and liver xanthine oxidase(XOD)level;take part of the liver and kidney for paraffin section and staining to observe the condition of the kidney and liver;take part of the kidney and small intestine for western blot and real-time fluorescence quantitative PCR to detect genes such as URAT1,UAT,OAT4,ABCG2 related to uric acid metabolism mRNA expression and protein expression.2.Adopt adenosine-induced hyperuric acid model of renal HK-2 cells.CCK-8 method was used to determine the dosage of Coix Seed Papaya Huazhuo Decoction,Coix Seed,Papaya and Poria cocos.3.The inhibitory effect of Coix Seed Papaya Huazhuo Decoction on xanthine oxidase in vitro was measured using a UV spectrophotometer.Results:1.The SUA,Cr,BUN,serum XOD,and liver XOD of the model mice were significantly higher than those of the blank group.The hyperuricemia mouse model was successfully constructed.2.After 28 days of Chinese herbal compound intervention,compared with the model group,Coix Papaya Huazhuo Decoction can significantly reduce SUA,Cr,BUN,serum XOD,and liver XOD levels in mice.3.Coix seed papaya Huazhuo decoction can reduce liver and kidney damage caused by high uric acid levels.4.Compared with the model group,Coix Seed Papaya Huazhuo Decoction can significantly reduce the levels of inflammatory factors TNF-? and IL-6 and reduce the inflammatory response.5.Compared with the model group,Coix Papaya Huazhuo Decoction can significantly increase the expression of ABCG2 and UAT in the kidneys of mice,reduce the expression of URAT1 and OAT4,upregulate the expression of ABCG2 in the intestine of mice,promote uric acid excretion,and reduce uric acid reabsorption.In order to adjust the metabolism of uric acid,it can reduce the effect of uric acid.6.Coix seed papaya Huazhuo decoction has obvious inhibitory effect on xanthinase in vitro.By inhibiting the activity of xanthine oxidase,it can reduce uric acid production and lower uric acid level in the body.7.Coix seed papaya Huazhuo decoction down-regulates the URAT1 expression of HK-2 cells in a cellular hyperuricemia model,reduces uric acid reabsorption,and reduces cellular uric acid levels.Conclusion:1.Coix seed papaya Huazhuo decoction can significantly reduce the body's uric acid level.The mechanism may be related to its ability to regulate the expression of URAT1,OAT4,ABCG2,UAT,and inhibit the activity of xanthine oxidase.2.Coix seed papaya Huazhuo decoction can slow down liver and kidney damage,and its mechanism may be related to its ability to reduce the levels of inflammatory factors TNF-?,IL-6,and body creatinine.