Yu-fei Guo, Ying Liu, Hao Zhang, Meng-yang Wang, Di Yang, Hai-ming Sun, Wei Liu
Natural polysaccharides are a class of bioactive macromolecules derived from medicinal plants, animals and fungi, characterized by high safety, strong biodegradability, and structural diversity. Their mechanisms of action involve multiple targets and pathways, and they exhibit low toxicity. In particular, their therapeutic efficacy is significantly enhanced following chemical modification or combination therapy. Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia resulting from impaired insulin secretion or signaling pathways. Existing research indicates that natural polysaccharides exert significant antidiabetic effects through mechanisms such as regulating lipid metabolism, providing antioxidant effects, improving insulin resistance (IR), and inhibiting inflammatory responses. This review summarizes the latest research advances on natural polysaccharides in the field of DM, focusing on the structure-activity relationship to reveal the influence of specific structural features on hypoglycemic activity. Based on their multi-target properties, it further elucidates the molecular mechanisms by which natural polysaccharides intervene in DM and its complications, including nephropathy, retinopathy, neuropathy, and cardiomyopathy. In conclusion, this review highlights the unique value of natural polysaccharides in the prevention and treatment of DM, particularly their role in regulating key metabolic signaling pathways, thereby providing a theoretical basis for future research and development in this field. • Natural polysaccharides play a crucial role in the treatment of diabetes. • The hypoglycemic activity of natural polysaccharides is closely related to their structure-activity relationship. • The structure-activity relationship of natural polysaccharides is crucial for treating diabetes. • Natural polysaccharides can be applied to diabetes and its complications.