Intervention Effect Of Fermented Morinda Citrifolia Juice On Hyperuricemia And Its Related Mechanism

Hyperuricemia has become a widely concerned health problem in recent years because of its increasing incidence in the world and the rising trend in young people.However,there are few drugs that can effectively reduce serum uric acid without causing liver and kidney damage.Therefore,it is of great significance to explore new ways to reduce serum uric acid.Modern pharmacological experiments show that morinda citrifolia has anti-inflammatory,anti-oxidant and immunomodulatory effects.Recent studies show that morinda citrifolia juice can also improve hyperuricemia and gout-like diseases,which may become a new method to relieve and treat hyperuricemia.Therefore,it is of great significance to clarify the effect of fermented morinda citrifolia juice(FNJ)on hyperuricemia and its mechanism.Firstly,male Kunming mice were selected as experimental animals,and the hyperuricemia model of mice was established by intragastric administration of Potassium oxonate(PO).Serum Uric acid(UA),Creatinine(Cr),Blood urea nitrogen(BUN),and Xanthine oxidase(XO)in serum and liver were measured.The results of animal experiments show that FNJ can significantly reduce the levels of serum UA,Cr and BUN in hyperuricemic mice,and can effectively inhibit the XO activity in serum and liver of hyperuricemic mice.The results of renal tissue section show that FNJ has renal protective effect and can alleviate renal injury caused by hyperuricemia.The results of Western Blot and q PCR showed that FNJ could significantly down-regulate the expression of Urate anion transporter 1(URAT1)and Glucose transporter 9(GLUT9)related to renal tubular reabsorption of uric acid.FNJ significantly increased the expression of Organic anion transporter 1(OAT1)and Organic anion transporter 3(OAT3)which can secrete uric acid.Micro RNA(mi RNA)sequencing and expression change analysis were carried out in mouse serum,and some differentially expressed mi RNAs were screened out.Based on GO and KEGG databases,the function enrichment analysis of differentially expressed mirna target genes revealed the related pathways and mechanisms of hyperuricemia in mice,and the possible mechanism of FNJ in reducing uric acid in hyperuricemia.Secondly,the hyperuricemia model of HK-2 cells was established by adenosine combined with XO.The cytotoxicity of FNJ to HK-2 cells was detected by CCK-8experiment.The uric acid content in the supernatant of HK-2 cell culture medium after FNJ intervention and the expression levels of URAT1 and GLUT9 in cells were detected by Western blot to verify the uric acid reducing effect of FNJ on hyperuricemia HK-2 cells.When the concentration of FNJ was lower than 60μL/m L,FNJ showed no cytotoxicity.After FNJ intervention,the uric acid content in the supernatant of cell culture solution decreased significantly in a dose-dependent manner.By detecting the expression levels of interleukin-1β(IL-1β)and Tumor necrosis factor-α(TNF-α)in HK-2 cells,it is proved that FNJ can significantly inhibit the expression levels of IL-1β and TNF-α in the hyperuricemia HK-2cell model,and determine the inflammation of FNJ in hyperuricemia HK-2 cells.By detecting the expression level of phosphorylated nuclear transcription factor kappa B(NF-κB)p-p65/p65 in HK-2 cells,it was verified that FNJ could alleviate the inflammatory reaction caused by hyperuricemia by inhibiting the expression of p-p65/p65 in NF-κB signaling pathway.Studies have shown that FNJ can reduce uric acid in hyperuricemic HK-2 cells,and inhibit inflammatory reaction by regulating NF-κB signaling pathway,thus playing a protective role.This study investigated the interventional effects of FNJ on hyperuricemia and its mechanism at animal,cellular and molecular levels,providing a theoretical basis for the development and application of FNJ to alleviate and treat hyperuricemia.