Na Wang, Wendi Xu, Wenxi Duan, Jingyi Qin, Haibo Huang, Jingjing Liu, Lijuan Zhu, Wenzhou Xiang
The increasing global prevalence of type 2 diabetes mellitus (T2DM) and the limitations of current treatments have spurred the quest for safe and efficient alternatives. Marine algae polysaccharides (MAP), obtained from brown, red and green algae, have emerged as promising natural candidates due to their diverse structures, bioavailability and varied biological activities. This review offers a thorough analysis of the potential of MAP in combating T2DM, covering their extraction, identification, molecular mechanisms and structure-activity relationships. The study commences by outlining the classification, structural features, advanced extraction and purification methods of MAP. The core of the review systematically explains the multifaceted mechanisms through which MAP combat T2DM, such as inhibiting digestive enzymes, improving insulin sensitivity through key pathways, safeguarding pancreatic β-cells and modulating gut microbiota-host metabolism. Additionally, the study explores structure-activity relationships, emphasizing how factors such as molecular weight, monosaccharide composition, glycosidic linkages, conformation and chemical modifications significantly impact their ability to lower blood sugar levels. Key findings indicate that low-to-moderate molecular weight (Mw) MAP with high sulfation degree and fucose/galactose enrichment exhibit superior enzyme inhibitory and insulin-sensitizing effects, while high-Mw fractions excel in gut microbiota modulation via fermentation. This review establishes a comprehensive and translational theoretical framework that bridges fundamental polysaccharide research with high-impact biomedical applications, offering crucial insights to guide the rational design and translational advancement of MAP-based therapies or nutraceuticals for managing T2DM.