Fucoidan alleviates renal fibrosis in mice via Akkermansia muciniphila-mediated suppression of NEU1-TLR4-NFκB signaling axis

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-07-07 DOI:10.1016/j.phymed.2025.157060

Zhen Wang , Xiao-Ling Rong , Cai-Xia Dai , Qing Wang , Lin-Feng Lu , Wen-Tao Zhang , Lei Zhang , Qian-Qian Chen , E-Hu Liu

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引用次数: 0

Abstract

Background

Fucoidan, a bioactive sulfated polysaccharide, is renowned for its extensive range of biological activities, including anticancer activity, antioxidative properties, immune activation and has demonstrated supportive therapeutic effects in treating kidney ailments. However, the underlying mechanism related to renal fibrosis remains not fully understood.

Purpose

The aim of this study was to elucidate the protective effects and mechanism of FPS against renal fibrosis with a focus on gut-kidney axis.

Methods

We established renal fibrosis models in mice using unilateral ureteral obstruction (UUO), folic acid (FA) challenge, or a microbiota-depleted, with continuous oral administration of FPS, Akkermansia muciniphila (AKK), or acetate at specified doses and intervals. Simultaneously, we examined the impact of FPS on epithelial mesenchymal transformation in cultured HK-2 and investigated the associated mechanisms.

Results

In this study, we demonstrate that fucoidan administration reduces renal collagen deposition, inflammation, epithelial mesenchymal transformation and improves renal function in mouse models of renal fibrosis induced by UUO or FA. Metagenomics analysis showed that fucoidan significantly increases the abundance of AKK by promoting its growth in UUO-induced renal fibrosis. Oral administration of live AKK alleviates renal fibrosis in UUO and FA mouse models. Using oral antibiotic-treated mice, we found that the effect of fucoidan on renal fibrosis was weakened. Gas chromatography-mass spectrometry (GC–MS/MS) study results show that AKK produces the short-chain fatty acids (acetate), which protects against renal fibrosis by suppressing NEU1-TLR4-NFκB-mediated inflammation in the kidney.

Conclusion

Our findings establish a novel gut-kidney axis wherein fucoidan ameliorates renal fibrosis through AKK-mediated acetate production and subsequent NEU1-TLR4-NFκB pathway inhibition.

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岩藻糖聚糖通过嗜粘蛋白Akkermansia介导的NEU1-TLR4-NFκB信号轴的抑制减轻小鼠肾纤维化

岩藻多糖是一种具有生物活性的硫酸酸化多糖，以其广泛的生物活性而闻名，包括抗癌活性、抗氧化特性、免疫激活，并已证明在治疗肾脏疾病方面具有支持治疗作用。然而，与肾纤维化相关的潜在机制尚不完全清楚。目的以肠肾轴为研究对象，探讨FPS对大鼠肾纤维化的保护作用及其机制。方法采用单侧输尿管梗阻（UUO）、叶酸（FA）刺激或微生物群衰竭的方法，在规定剂量和间隔时间内连续口服FPS、嗜muciniphila （AKK）或醋酸酯，建立小鼠肾纤维化模型。同时，我们研究了FPS对培养HK-2上皮间充质转化的影响，并探讨了相关机制。结果在本研究中，我们证明岩藻糖聚糖可以减少UUO或FA诱导的肾纤维化小鼠模型中的肾脏胶原沉积、炎症、上皮间质转化和改善肾功能。宏基因组学分析显示，岩藻糖聚糖通过促进AKK在uuo诱导的肾纤维化中的生长，显著增加AKK的丰度。口服活AKK可减轻UUO和FA小鼠模型的肾纤维化。用口服抗生素治疗的小鼠，我们发现岩藻糖聚糖对肾纤维化的作用减弱。气相色谱-质谱联用（GC-MS /MS）研究结果表明，AKK产生短链脂肪酸（醋酸酯），通过抑制neu1 - tlr4 - nfκ b介导的肾脏炎症来预防肾纤维化。我们的研究结果建立了一个新的肠-肾轴，其中岩藻糖聚糖通过akk介导的醋酸盐生成和随后的NEU1-TLR4-NFκB通路抑制来改善肾纤维化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.