Zhou Liquan, Li Jiani, Ding Chen, Zhou Yimiao, Xiao Zuowei
Homologous Innovation Laboratory of Medicine and Food, Hunan University of Chinese Medicine, Changsha 410208, China.
Hunan Engineering and Technology Research Center for Health Products and Life Science, Hunan University of Chinese Medicine, Changsha 410208, China.
Molecules. 2025 Apr 29;30(9):1980. doi: 10.3390/molecules30091980.
Natural polysaccharides (NPs), as a class of bioactive macromolecules with multitarget synergistic regulatory potential, exhibit significant advantages in diabetes intervention. This review systematically summarizes the core hypoglycemic mechanisms of NPs, covering structure-activity relationships, integration of the gut microbiota-metabolism-immunity axis, and regulation of key signaling pathways. Studies demonstrate that the molecular weight, branch complexity, and chemical modifications of NPs mediate their hypoglycemic activity by influencing bioavailability and target specificity. NPs improve glucose metabolism through multiple pathways: activating insulin signaling, improving insulin resistance (IR), enhancing glycogen synthesis, inhibiting gluconeogenesis, and regulating gut microbiota homeostasis. Additionally, NPs protect pancreatic β-cell function via the nuclear factor E2-related factor 2 (Nrf2)/Antioxidant Response Element (ARE) antioxidant pathway and Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) anti-inflammatory pathway. Clinical application of NPs still requires overcoming challenges such as resolving complex structure-activity relationships and dynamically integrating cross-organ signaling. Future research should focus on integrating multi-omics technologies (e.g., metagenomics, metabolomics) and organoid models to decipher the cross-organ synergistic action networks of NPs, and promote their translation from basic research to clinical applications.
天然多糖（NPs）作为一类具有多靶点协同调节潜力的生物活性大分子，在糖尿病干预方面具有显著优势。本综述系统总结了NPs的核心降糖机制，包括结构-活性关系、肠道微生物群-代谢-免疫轴的整合以及关键信号通路的调节。研究表明，NPs的分子量、分支复杂性和化学修饰通过影响生物利用度和靶点特异性来介导其降糖活性。NPs通过多种途径改善葡萄糖代谢：激活胰岛素信号、改善胰岛素抵抗（IR）、增强糖原合成、抑制糖异生以及调节肠道微生物群稳态。此外，NPs通过核因子E2相关因子2（Nrf2）/抗氧化反应元件（ARE）抗氧化途径和Toll样受体4（TLR4）/核因子-κB（NF-κB）抗炎途径保护胰腺β细胞功能。NPs的临床应用仍需克服诸如解决复杂的结构-活性关系和动态整合跨器官信号等挑战。未来的研究应集中于整合多组学技术（如宏基因组学、代谢组学）和类器官模型，以破译NPs的跨器官协同作用网络，并促进其从基础研究向临床应用的转化。
