Zhang Nanhai, Zhou Jingxuan, Zhao Liang, Zhao Zhen, Wang Shiran, Zhang Liebing, Zhou Feng
Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, People's Republic of China.
Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing 100048, People's Republic of China.
Food Funct. 2023 Feb 6;14(3):1710-1725. doi: 10.1039/d2fo03332a.
The prevalence of hyperuricemia (HUA) has been rising, and it is typically accompanied by renal injury and intestinal flora disorder, leading to a non-negligible health crisis. Ferulic acid (FA), as a familiar polyphenol, has been proven to exert anti-hyperuricemic properties inhibiting uric acid (UA) synthesis; however, the detailed underlying mechanisms remain unclear. The aim of this study was to explore the regulatory effect of FA on UA excretion as a potential strategy for reducing UA levels, and the comorbidities of HUA. FA treatment downregulated the expression of urate absorption transporter genes and repressed the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway in UA-stimulated HK-2 cells. To examine these effects , FA or allopurinol (positive control) was given to rats with HUA induced by a high-fructose/fat diet (HFFD) for 20 weeks. FA markedly decreased the serum UA, blood urea nitrogen, and creatinine levels. The expression of urate absorption transporters was downregulated, whereas the expression of secretion transporters was upregulated in the kidneys and intestines of FA-treated HUA rats. Additionally, FA mitigated renal oxidative stress, and suppressed the activation of the TLR4/NF-κB pathway and the downstream inflammatory response-related markers in the kidneys. Moreover, FA remodeled the composition of the gut microbiota, characterized by an increase in beneficial bacteria (, and ) and a decrease in pathogenic bacteria (, ). In conclusion, our study validated FA as an effective nutrient to ameliorate HFFD-induced HUA, suggesting its potential to mitigate the HUA-associated renal impairment and intestinal microbiota disturbance.
高尿酸血症（HUA）的患病率一直在上升，并且通常伴有肾损伤和肠道菌群紊乱，导致了一场不可忽视的健康危机。阿魏酸（FA）作为一种常见的多酚，已被证明具有抗高尿酸血症的特性，可抑制尿酸（UA）合成；然而，其具体的潜在机制仍不清楚。本研究的目的是探讨FA对UA排泄的调节作用，作为降低UA水平及HUA合并症的一种潜在策略。FA处理下调了尿酸吸收转运蛋白基因的表达，并抑制了UA刺激的HK-2细胞中Toll样受体4（TLR4）/核因子κB（NF-κB）通路。为了研究这些作用，将FA或别嘌醇（阳性对照）给予由高糖/高脂饮食（HFFD）诱导的HUA大鼠20周。FA显著降低了血清UA、血尿素氮和肌酐水平。在FA处理的HUA大鼠的肾脏和肠道中，尿酸吸收转运蛋白的表达下调，而分泌转运蛋白的表达上调。此外，FA减轻了肾脏氧化应激，并抑制了肾脏中TLR4/NF-κB通路的激活及下游炎症反应相关标志物。而且，FA重塑了肠道微生物群的组成，其特征是有益菌（如 、 和 ）增加，致病菌（如 、 ）减少。总之，我们的研究证实FA是一种有效改善HFFD诱导的HUA的营养素，表明其有减轻HUA相关肾损伤和肠道微生物群紊乱的潜力。
