Mechanism Of Fucoidan From Laminaria Japonica Against Hyperuricemia In Mice

Hyperuricemia is one of the major diseases that threaten human life and health at present,it is closely related to many diseases like gout,hypertension,diabetes,hyperlipidemia,coronary heart disease and other metabolic diseases,also can damage the kidneys,cause a series of kidney disease.But the treatment has many side effects on the body,so it is of great significance to explore the natural drugs which can reduce uric acid and have less side effects on the body.Study confirmed that fucoidan from Laminaria japonica in patients with hyperuricemia can regulate the serum creatinine and urea nitrogen levels,as a treatment drug for kidney related diseases caused by hyperuricemia,but the study of its role of lowering uric acid is still relatively few.This experiment is intended to explore the reduction effect of fucoidan from Laminaria japonica to uric acid,and study on the related regulation mechanism of synthetic metabolism and renal excretion of uric acid in the body.In addition,from the angle of the sex hormones can affect the metabolism of uric acid to explore the influence of fucoidan from Laminaria japonica on gonad axis and further control the change of uric acid content.In order to study the reduction effect of fucoidan from Laminaria japonica to uric acid,FL was obtained by ultrasonic composite enzymatic extraction and ethanol precipitation,the sulfate content determination was 11.01%,L-fucose content was 19.04%,uronic acid content was 4.27% and protein content was 1.23%,then two component elution FL1 and FL2 were got through column chromatography classification,HPGPC method measuring weight-average molecular weight of FL1 and FL2 were 5.6 kDa and 0.9 kDa.The hyperuricemia mice were fed with different doses of FL.The serum index,liver and renal function indexes of hyperuricemia mice were measured.Results showed that,compared with the model group,FL could decreased the levels of serum uric acid,creatinine,urea nitrogen and activites of GOT,GPT significantly(p<0.01),and effectively relieve the oxidative damage on liver and kidney tissue in hyperuricemia mice,increased the activities of SOD and CAT in liver and kidney tissues while decreased the content ofMDA in mice.The degree of renal interstitial fibrosis,tubular basement membrane thickening were alleviated,tubulo interstitial cells decreased.These results suggest that fucoidan from Laminaria japonica has the effect of lowering uric acid,and has the recovery effect on the damage of liver and kidney in hyperuricemia mice to a certain extent,the best dose is 150 mg/kg.Then the serum sex hormone level,testis sex hormone levels and oxidative stress in liver tissue and other related indicators,enzyme activity of uric acid metabolism in liver tissues,expression of renal urate transporter were measured.Results show that compared with the model group,FL can regulate the serum sex hormone anomalous change and alleviate oxidative stress damage of testis tissue in hyperuricemia mice to promote the metabolism of uric acid,such as it can significantly reduce the levels of serum estradiol,luteinizing hormone,testosterone,follicle stimulating hormone(p<0.01),significantly increase the activities of CAT and SOD(p<0.01),while reduce the activities of MDA of esticular tissuet(p<0.01),relieve the oxidative stress damage of testicular tissue.Also can significantly reduce the activityies of XOD and ADA in hyperuricemia mice,thereby to regulate metabolismuric of acid in the body.Using Western blot to analyze the change of urate transporter in the kidney,the results show that FL can raise urate transporter UAT expression capacity,lower the expression of urate anion transporter URAT1 and organic anion transporter OAT4,to reduce the weight of uric acid absorption as well as promote the excretion of uric acid,to achieve the effect of reducing uric acid.In conclusion,FL can effectively reduce the level of serum uric acid,the mechanism of lowering uric acid probably because it can improve liver function and regulate activity of enzyme in liver which associated with the uric acid metabolism,alleviate the oxidative damage of testicular and regulate the balance of serum sex hormon,reduce the pathological damage and oxidative stress injury,and regulate the expression quantity of urate transportern in renal.