Qi Xiaofen, Guan Kaifang, Liu Chunhong, Chen Haoran, Ma Ying, Wang Rongchun
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, Heilongjiang, China.
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, Heilongjiang, China.
J Dairy Sci. 2023 Nov;106(11):7367-7381. doi: 10.3168/jds.2023-23369. Epub 2023 Aug 9.
Pro-Glu-Trp (PEW) and Leu-Leu-Trp (LLW) are peptides derived from whey protein digestive products; both peptides exhibit xanthine oxidase inhibitory activity in vitro. However, it remains unclear whether these peptides can alleviate hyperuricemia (HUA) in vivo. In this study, we investigated the roles of PEW and LLW, both individually and in combination, in alleviating HUA induced by potassium oxonate and hypoxanthine. Together, PEW and LLW exhibited synergistic effects in reducing the serum levels of uric acid (UA), creatinine, and blood urea nitrogen, as well as increasing the fractional excretion of UA. The combined treatment with PEW and LLW inhibited UA synthesis, promoted UA excretion, and restored renal oxidative stress and mitochondrial damage. Moreover, the combined treatment alleviated dysbiosis of the gut microbiota, characterized by increased helpful microbial abundance, decreased harmful bacterial abundance, and increased production of short-chain fatty acids. Taken together, these results indicate that the combination of PEW and LLW mitigate HUA and kidney injury by rebalancing UA synthesis and excretion, modulating gut microbiota composition, and improving oxidative stress.
脯氨酸-谷氨酸-色氨酸（PEW）和亮氨酸-亮氨酸-色氨酸（LLW）是源自乳清蛋白消化产物的肽；这两种肽在体外均表现出黄嘌呤氧化酶抑制活性。然而，这些肽在体内是否能缓解高尿酸血症（HUA）仍不清楚。在本研究中，我们分别及联合研究了PEW和LLW在减轻氧嗪酸钾和次黄嘌呤诱导的HUA中的作用。PEW和LLW共同作用在降低血清尿酸（UA）、肌酐和血尿素氮水平以及增加UA分数排泄方面表现出协同效应。PEW和LLW联合治疗抑制了UA合成，促进了UA排泄，并恢复了肾脏氧化应激和线粒体损伤。此外，联合治疗减轻了肠道微生物群的失调，其特征为有益微生物丰度增加、有害细菌丰度降低以及短链脂肪酸产量增加。综上所述，这些结果表明，PEW和LLW联合使用可通过重新平衡UA合成与排泄、调节肠道微生物群组成以及改善氧化应激来减轻HUA和肾脏损伤。
