Zhang Yating
College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, Changsha, Hunan, China.
Front Cell Infect Microbiol. 2025 Jul 10;15:1626614. doi: 10.3389/fcimb.2025.1626614. eCollection 2025.
Ulcerative colitis (UC), a chronic inflammatory bowel disease driven by gut dysbiosis, immune dysregulation, and oxidative stress, lacks universally effective therapies. Fucoidan (FCD), a sulfated polysaccharide derived from brown algae, has emerged as a multifaceted therapeutic candidate due to its anti-inflammatory, antioxidant, and immunomodulatory properties. This review synthesizes FCD's mechanisms in UC pathogenesis, emphasizing its suppression of NF-κB and MAPK signaling pathways to reduce proinflammatory cytokines (e.g., IL-6, TNF-α) and regulate TLR-mediated macrophage polarization. FCD enhances intestinal barrier integrity via upregulation of tight junction proteins (Claudin-1, ZO-1) and mucin MUC2 expression, while remodeling gut microbial ecology through enrichment of SCFAs-producing bacteria (e.g., Ruminococcaceae) and suppression of pathogens (Escherichia coli, Candida albicans). Preclinical studies highlight LMWF as a superior candidate, demonstrating enhanced bioavailability and efficacy in mitigating DSS-induced colitis. Despite its promise, challenges persist in structural heterogeneity (source- and extraction-dependent), scalable production of LMWF, and insufficient pharmacokinetic data. Emerging strategies-including nanoparticle-based delivery systems and structural modifications (cross-linking, covalent bonding)-aim to overcome bioavailability limitations. This review underscores FCD's potential as a functional food or adjuvant therapy for UC, while advocating for rigorous clinical validation to bridge translational gaps, Enrichment of SCFAs-producing taxa and suppression of pathobionts (, ), mediated through prebiotic fermentation. Suppression of NF-κB activation via IκBα stabilization and inhibition of p65 nuclear translocation, and downregulation of MAPK phosphorylation (ERK1/2, JNK, p38), reducing proinflammatory cytokines (IL-6, TNF-α, IL-1β). FCD can be used as a potential treatment for UC.
溃疡性结肠炎（UC）是一种由肠道微生物失调、免疫调节紊乱和氧化应激驱动的慢性炎症性肠病，目前缺乏普遍有效的治疗方法。岩藻依聚糖（FCD）是一种从褐藻中提取的硫酸化多糖，因其具有抗炎、抗氧化和免疫调节特性，已成为一种具有多方面治疗潜力的候选药物。本综述综合阐述了FCD在UC发病机制中的作用机制，重点强调了其对NF-κB和MAPK信号通路的抑制作用，以减少促炎细胞因子（如IL-6、TNF-α）的产生，并调节TLR介导的巨噬细胞极化。FCD通过上调紧密连接蛋白（Claudin-1、ZO-1）和粘蛋白MUC2的表达来增强肠道屏障的完整性，同时通过富集产生短链脂肪酸的细菌（如瘤胃球菌科）和抑制病原体（大肠杆菌、白色念珠菌）来重塑肠道微生物生态。临床前研究表明低分子量岩藻依聚糖（LMWF）是一种更优的候选药物，在减轻右旋糖酐硫酸钠（DSS）诱导的结肠炎方面具有更高的生物利用度和疗效。尽管前景广阔，但仍存在一些挑战，包括结构异质性（取决于来源和提取方法）、LMWF的规模化生产以及药代动力学数据不足等问题。新兴策略，包括基于纳米颗粒的递送系统和结构修饰（交联、共价键合），旨在克服生物利用度限制。本综述强调了FCD作为UC功能性食品或辅助治疗药物的潜力，同时主张进行严格的临床验证以弥合转化差距，通过益生元发酵介导的产生短链脂肪酸的分类群的富集和致病共生菌的抑制。通过IκBα稳定化抑制NF-κB激活和抑制p65核转位，以及下调MAPK磷酸化（ERK1/2、JNK、p38），减少促炎细胞因子（IL-6、TNF-α、IL-1β）。FCD可作为UC的潜在治疗药物。
