Distinct anti-hyperuricemia mechanisms of polysaccharide-rich and non-polysaccharide fractions from Lentinula edodes water extract

IF 7.2 Q1 AGRICULTURE, MULTIDISCIPLINARY

Journal of Agriculture and Food Research Pub Date : 2026-08-01 Epub Date: 2026-07-23 DOI:10.1016/j.jafr.2026.103165

Xinyi Xiong, Peng Liu, Liping Liu, Jie Feng, Jie Geng, Jinyan Wang, Jingsong Zhang, Yanfang Liu

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Abstract

Hyperuricemia (HUA) is associated with excessive uric acid (UA) production, impaired excretion, and systemic metabolic disturbances. This study investigated the differential anti-HUA mechanisms of two fractions derived from Lentinula edodes (L. edodes) water extract (LEW): the ethanol-supernatant fraction (non-polysaccharide, LEPS) and the ethanol-precipitated fraction (polysaccharide-rich, LEP). Physicochemical characterization revealed marked compositional differences between the two fractions. LEP was highly enriched in carbohydrates (83.36%) and mainly consisted of heterogeneous high-molecular-weight polysaccharides, whereas LEPS contained a lower carbohydrate content (34.35%) and was dominated by low-molecular-weight constituents (M_w = 5.20 × 10² g/mol). In HUA rats, LEPS exhibited a superior UA-lowering efficacy, primarily attributed to potent inhibition of hepatic xanthine oxidase (XOD) activity, thereby suppressing UA production, along with marked amelioration of liver injury. In contrast, LEP played a major role in ameliorating renal injury, oxidative stress, and inflammation. Mechanistically, LEP effectively downregulated renal reabsorption transporters (URAT1, GLUT9), upregulated secretory transporters (OAT1, ABCG2), and enhanced intestinal barrier integrity via upregulating tight junction proteins. Multi-omics analysis revealed that LEPS mainly modulated amino acid and redox-related metabolic pathways (tyrosine, nicotinate metabolism), whereas LEP predominantly regulated lipid metabolism and inflammation-associated pathways (linoleic acid, arachidonic acid metabolism). Both fractions reshaped gut microbiota composition and increased total short-chain fatty acids (SCFAs) as well as specific beneficial bacteria such as Lachnospiraceae. In conclusion, L. edodes fractions exerted anti-HUA effects through differentiated mechanisms, supporting their targeted utilization in functional products for HUA management.

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香菇水提物富多糖和非多糖部位抗高尿酸血症的不同机制

高尿酸血症（HUA）与尿酸过量（UA）产生、排泄受损和全身代谢紊乱有关。研究了香菇水提物（LEW）乙醇上清部分（非多糖，LEPS）和乙醇沉淀部分（富多糖，LEP）的抗hua机制差异。理化性质表明，两个馏分的成分有明显的差异。LEPS的碳水化合物含量较高（83.36%），主要由异构的高分子量多糖组成，而LEPS的碳水化合物含量较低（34.35%），以低分子量组分为主（Mw = 5.20 × 102 g/mol）。在HUA大鼠中，LEPS表现出优越的降低UA的功效，主要归因于有效抑制肝黄嘌呤氧化酶（XOD）活性，从而抑制UA的产生，同时显著改善肝损伤。相比之下，LEP在改善肾损伤、氧化应激和炎症方面发挥了主要作用。在机制上，LEP有效下调肾重吸收转运蛋白（URAT1, GLUT9），上调分泌转运蛋白（OAT1, ABCG2），并通过上调紧密连接蛋白增强肠屏障完整性。多组学分析显示，LEPS主要调节氨基酸和氧化还原相关代谢途径（酪氨酸、烟酸代谢），而LEP主要调节脂质代谢和炎症相关途径（亚油酸、花生四烯酸代谢）。这两种组分都重塑了肠道菌群组成，增加了总短链脂肪酸（SCFAs）以及特定的有益细菌，如毛缕菌科。综上所述，香薷提取物通过不同的机制发挥抗HUA作用，支持其在HUA管理功能产品中的靶向利用。

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