Effects And Mechanisms Of Black Tea And Its Black Brick Tea With Fungus Growing On Lowering Uric Acid In Hyperuricemic Mice

Hyperuricemia is caused by excessive production of uric acid and/or reduced excretion of uric acid.With the improvement of the quality of public life and the significant changes in eating habits,the number of patients with hyperuricemia has increasing.At present,most of the drugs used to treat hyperuricemia in the clinic are western medicines.Although drugs have certain treatment effects on hyperuricemia,there are many side effects.Improving the dietary nutrition under the modern dietary structure and promoting the health of the body are important development direction of food nutrition intervention science.Dark tea is an unique post-fermented tea and black tea is a full-fermented tea in the Chinese traditional six kinds of teas,which have many biological activities such as prevention and treatment of cardiovascular and cerebrovascular diseases,lowering uric acid,lowering lipid and reducing weight.The black brick tea with fungus growing is a new kind of post-fermented black tea that adds processes of fungus growing and pressing on the basis of black tea.But whether it has a better effect of lowering uric acid than its black tea remains to be further explored.The study was based on the successful establishment of hyperuricemic model mice.Then the hyperuricemic model mice was intervened by three different doses about of black tea and its black brick tea with fungus growing(low dose of 0.5g·kg^-1·d^-1?middle dose of 1g·kg^-1·d^-1?high dose of 2g·kg^-1·d^-1)made from the same fresh leaves as raw materials for 14 days.And analyzed the weight change during feeding process and organ index,observing the pathological changes of renal used HE ateining,measured the levels of biochemical indicators such as the levels of serum uric acid used kits?the acitivities of xanthine oxidase?XOD?and adenosine deaminase?ADA?used kits,and the expression of Tumor necrosis factor-??TNF-??,Interleukin-1??IL-1??and Cyclooxygenase-2?COX-2?used Enzyme-Linked ImmunoSorbent Assay?ELISA?and analyzed the expression levels of uric acid transporters,inflammatory factors and signaling pathway related genes and proteins which were detected by quantitative real-time PCR?qRT-PCR?and western blot were aimed to investigate the effect and molecular mechanism of the two teas in lowering uric acid in hyperuricemic mice.The main results and conclusions were as follows:?1?Effects on lowering uric acid.The mice in the model group were treated with 250mg/kg potassium oxonate for 7 days.The results showed that compared with the normal group,the levels of serum uric acid in model group was significantly increased?P<0.05?,indicating that the method can successfully establish hyperuricemic mice.After intervention with hyperuricemic mice with black tea and its black brick tea with fungus growing,the results showed that compared with the model group,the levels of weight,kidney index and serum uric acid in tea-treated groups were significantly decreased?P<0.05?.And the middle and high dose groups of black brick tea with fungus growing had extremely significant reduction in serum uric acid?P<0.01?.Blood urea nitrogen and serum creatinine also were extremely significant decreased in tea-treated groups?P<0.01?.The levels of urine urea nitrogen in the middle and high dose groups were extremely significant increased?P<0.01?,and the levels of urine uric acid in the high dose groups were extremely significant increased?P<0.01?.The levels of urine creatinine had extremely significant increased in the tea-treated groups?P<0.01?,except the low-dose black tea group which was significantly increased?P<0.05?.The expressions of COX-2,TNF-?,IL-1?in the kidney of tea-treated groups were extremely significant decreased?P<0.01?.In addition,the results of HE staining showed that the kidney tissue of each group did not significantly change during the feeding process.?2?The molecular mechanisms on lowering uric acid.Compared with the model group,the activities of XOD and ADA in the middle and high dose groups of two teas were significantly decreased?P<0.05?.The mRNA expression levels of mURAT1 and mGLUT9were down-regulated to different extents and the protein expression levels were extremely significant down-regulated in tea-treated groups?P<0.01?.The mRNA and protein expression levels of mOAT1,mOAT3 and mOCT1 were up-regulated to some extents in tea-treated groups.The protein expression levels of mCOX-2,mTNF-?and mIL-1?in tea-treated groups were extremely significant decreased?P<0.01?,and the mRNA expression levels of mCOX-2,mTNF-??mIL-1??mTLR4?mMyD88?mNLRP3?mASC?mCaspase-1?mNF-?B p65?m IKK??m I?B?were decreased to some extents in tea-treated groups;The protein expression levels of mTLR4 and p-m-NF-?B p65/mNF-?B p65 were significantly down-regulated in tea-treated groups?P<0.05?.At the same time,except for the low-dose group of black brick tea with fungus growing,the protein expression level of mMyD88 in the other tea-treated groups were significantly down-regulated?P<0.05?.This indicates that both black tea and its black brick tea with fungus growing can reduce uric acid in hyperuricemic mice by inhibiting the production of uric acid and promoting the excretion of uric acid,and inhibiting the activation of NLRP3 inflammasome and TLR4/MyD88/NF-?B signaling pathway to improve kidney damage and alleviate the development of hyperuricemia,reduce the expression levels of COX-2,TNF-?,IL-1?.Black tea was superior to its black brick tea with fungus growing in up-regulating the expression level of mOAT3 and down-regulating the expression level of mTLR4.The low dose of black tea was superior to its black brick tea with fungus growing in inhibiting the protein expression levels of mMyD88 and mTNF-?.The high-dose black tea was superior to its black brick tea with fungus growing in inhibiting the protein expression level of mCOX-2.However the black brick tea with fungus growing was superior to the black tea in inhibiting the protein expression level of mURAT1.the high-dose black brick tea with fungus growing was superior to black tea in lowering serum uric acid?increasing urine uric acid?urine urea nitrogen and urine creatinine and the middle-dose black brick tea with fungus growing was superior to the corresponding dose of black tea in reducing the protein expression levels of mTNF-??mIL-1?.