Anti‐Hyperuricemic, Nephroprotective, and Gut Microbiota Regulative Effects of Separated Hydrolysate of α‐Lactalbumin on Potassium Oxonate‐ and Hypoxanthine‐Induced Hyperuricemic Mice

Abstract

This study aims to investigate the anti-hyperuricemic and nephroprotective effects and the potential mechanisms of the separated gastrointestinal hydrolysates of 𝜶-lactalbumin on hyperuricemic mice. Methods and results: The gastrointestinal hydrolysate of 𝜶-lactalbumin, the hydrolysate fraction with molecular weight (MW) < 3 kDa (LH-3k), and the fragments with smallest MW among LH-3K harvested through dextran gel chromatography (F5) are used. Hyperuricemia mice are induced via daily oral gavage of potassium oxonate and hypoxanthine. F5 displays the highest in vitro xanthine oxidase (XO) inhibition among all the fractions separated from LH-3k. Oral administration of F5 significantly reduces the levels of serum uric acid (UA), creatinine, and urea nitrogen. F5 treatment could ameliorate kidney injury through alleviating oxidative stress and inflammation. F5 alleviates hyperuricemia in mice by inhibiting hepatic XO activity and regulating the expression of renal urate transporters. Gut microbiota analysis illustrates that F5 administration increases the abundance of some SCFAs producers, and inhibits the growth of hyperuricemia and inflammation associated genera. LH-3k exhibits similar effects but does not show significance as those of the F5 fraction. Conclusion: The anti-hyperuricemia and nephroprotective functions of F5 are mediated by inhibiting hepatic XO activity, ameliorating oxidative stress and inflammation, regulating renal urate transporters, and modulating the gut microbiota in hyperuricemic mice.

Coffee Leaf Tea Extracts Improve Hyperuricemia Nephropathy and Its Associated Negative Effect in Gut Microbiota and Amino Acid Metabolism in Rats

“…However, TE lowered ALT and AST activities and prevented hepatic pathological changes. Serum CR and BUN are positively related to kidney injury . They were significantly increased after HN modeling in the current study ( p < 0.01; Figure g,h).…”

“…Serum CR and BUN are positively related to kidney injury. 20 They were significantly increased after HN modeling in the current study (p < 0.01; Figure 2g,h). In addition, the histopathological image of the kidney (Figure 2j) showed that extensive fibrous tissue proliferation with a small quantity of inflammatory cell infiltration was observed in the MC group (red arrows).…”

Milk Bioactive Compounds and Gut Microbiota Modulation: The Role of Whey Proteins and Milk Oligosaccharides

“…Importantly, α-lactalbumin and some of its bioactive peptides have been shown to play a role in the modulation of the gut microbiota by acting as prebiotics ( Table 3 ), and studies suggest this is related both to a direct promotion of probiotics’ growth, including bifidobacteria, and, indirectly, to their antimicrobial activity against diverse pathogens [ 172 , 174 , 175 , 176 ]. Xie et al demonstrated that hyperuricemic mice orally administered with α-lactalbumin gastrointestinal hydrolysates showed a reduction in the levels of serum uric acid, creatinine, and urea nitrogen in association with an increased abundance of some SCFA-producing bacteria, and a decrease of the growth of hyperuricaemia- and inflammation-associated genera [ 177 ]. In a previous study, Xie and colleagues demonstrated that treatment with α-lactalbumin hydrolysates is effective in alleviating hypertension-associated intestinal microbiota dysbiosis in spontaneously hypertensive rats [ 178 ].…”

WITHDRAWN: The anti-hyperuricemic and gut microbiota regulatory effects of a novel purine assimilatory probiotic strain

“…The nal total protein concentration reached 3.33 mg/mL by adding SDS-PAGE buffer. The following experiments were performed using our previous method [21]. The expression levels of GLUT9, URAT1 and OAT1 were analyzed.…”