| Hyperuricemia(HUA)is a common disorder of purine metabolism that is common worldwide due to excessive uric acid production in the body and decreased excretion.Inhibition of hepatic uric acid synthesis of key enzyme activity and increased expression of renal uric acid transporters are seen as targets for drug intervention HUA.Allopurinol(AP),benzbromarone,and other drugs have been used to treat HUA,and their role is mainly to inhibit the activity of key enzymes in uric acid production and promote uric acid excretion,but side effects are inevitable.Recent studies have shown that dietary polyphenols have the effect of preventing and alleviating HUA,and diet is closely related to the community structure of the gut microbiome.Therefore,dietary interventions are one of the most promising strategies for preventing hyperuricemia and controlling uric acid concentrations,and the gut microbiome is also a potential target for the prevention of HUA and the regulation of metabolism.Regulating hepatic-renal-intestinal axis metabolism is considered an effective way to prevent and alleviate HUA.Tea(Camellia sinesis)contains many functional ingredients such as tea polyphenols,alkaloids,amino acids.Nowadays,the pressure on social work is greater,and natural health drinks such as tea and coffee are more and more popular among consumers.Tea can be divided into six categories according to its different processing processes: green tea,white tea,black tea,dark tea,yellow tea,and oolong tea.Among them,extracts of black tea,dark tea,green tea and oolong tea,tea polyphenols,and thearubigins have been used to study the effect on HUA,while the effect of other tea types on HUA has not been reported.Amino acids are important functional components in tea,and studies have shown that ingestion of tea may enhance the amino acid metabolism pathway of HUA mice,suggesting that the regulatory effect of amino acid components on HUA in tea is worth exploring.In addition,studies have reported that tea has a significant effect on preventing and alleviating metabolic diseases and regulating intestinal microorganisms,but the research has focused on green tea or polyphenol substances,and there are fewer studies on tea amino acids on intestinal microorganisms.At the same time,the gut microbiome and its involved amino acid metabolism play an important role in the pathogenesis of HUA.Therefore,it is necessary to explore the regulatory effect of highamino acid tea on the HUA intestinal microbiome.In this paper,the effects of high-amino acid green tea extract on HUA were studied,and its uric acid-lowering effects and the optimal dose were clarified for the baseline subsequent concentrations of TEs of high amino acids and high tea polyphenols.Then,with three tea extracts(Tea extracts,TEs)with different amino acid polyphenol content as treatment,the role of high amino acid TE and high tea polyphenol TE in the hepatickidney-intestinal axis metabolism of HUA mice induced by potassium oxonate(PO)and its regulatory effect on intestinal microorganisms were studied,and the effect of high concentration of amino acids and tea polyphenols on HUA was observed.Finally,the interaction between small molecules in TEs and Xanthine oxidase(XOD)was simulated by molecular docking technology,and the role of amino acids and tea polyphenol small molecules in inhibiting liver XAD was explored,which provided a basis for screening out the components of tea for the treatment and treatment of HUA.The main research contents and achievements are as follows:1.Three kinds of green tea extracts(DJT,HJT,and CQT)with different contents of amino acids and polyphenols were prepared by hot water extraction.The contents of Catechin,caffeine,and amino acid were determined by High-performance liquid chromatography.The results showed that DJT had the highest content of free amino acids and HJT had the highest content of polyphenol.2.The effect of high amino acid green tea extract(HJT)on HUA was studied in mice,and the optimum concentration was selected.The results showed that high amino acid HJT tea extract could significantly reduce uric acid in vivo and inhibit the key enzyme activity of uric acid production in the liver of HUA mice.At the same time,1000mg/kg tea extract was better than 500 mg/kg and 2000 mg/kg tea extract.3.Using 1000 mg/kg HJT as the middle control group,the mice experiment with green tea with high amino acid and low polyphenol and high polyphenol was further showed that the extract of green tea with low amino acid and the high amino acid was better than that of green tea with high amino acid,three kinds of tea extracts all alleviated the increase of uric acid and inhibited the activity of XOD in mice,down-regulated the expression of urate reuptake protein URAT1 and urate excretion protein ABCG2 in kidney and small intestine,it also modulates the uric acid metabolism-related microbiome in HUA mice.Among them,DJT with high amino acid and low polyphenol had no significant difference in lowering uric acid and protecting kidneys compared with CQT with high polyphenol and low polyphenol,but it had a more significant effect on regulating microbiome and SCFAs content.The results also showed that the effects of TEs on the regulation of Intestinal Microflora were different,and the control groups with similar contents(such as DJT and HJT,HJT and CQT)showed similar effects on the regulation of the composition of special bacteria,it is suggested that the concentrations of amino acid and tea polyphenol in tea may have different effects on HUA.4.The binding effect of nine main tea small molecules in TEs amino acids,catechins,and alkaloids with XOD was studied by molecular docking technology.These include Theanine,Glutamic acid,Aspartic acid,Serine,γ-aminobutyric acid(GABA),Epigallocatechin gallate(EGCG),Epicatechin gallate(ECG),Epicatechin(EC),and Epigallocatechin(EGC).The lowest binding energy of all docking sites was negative,which indicated that XOD could spontaneously bind to XOD and formed a hydrogen bond with amino acid residues by entering the hydrophobic cavity of the molybdenum active site of XOD,thus preventing Xanthine from entering the active site,competitive Inhibition,which acts as an oxidant of xanthine to uric acid,tested the inhibitory activity of three green tea extracts on XOD in mice.The results also showed that the interaction of catechin micromolecule with XOD is better than that of amino acid micromolecules,especially EGCG and ECG.Further studies on HUA will focus on the inhibitory effect of ester catechin on XOD in vitro and in vivo. |
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