Molecular mechanism and structure-activity relationships of natural source polysaccharides in intervening type 2 diabetes mellitus through antioxidant effects: A systematic review.

Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder closely associated with oxidative stress. Natural source polysaccharides (NSPs) show great potential in T2DM management due to their remarkable antioxidant activity and favourable biosafety. This review systematically elaborates the multi-target mechanisms and structure-activity relationships of NSPs against T2DM. Key mechanisms include regulating oxidative stress, modulating insulin/PI3K/Akt signalling, inhibiting α-glucosidase/α-amylase, protecting pancreatic β-cells, and improving hepatic lipid metabolism. Furthermore, through cluster analysis and structural visualization, we delineate the critical influence of molecular weight, monosaccharide composition, and glycosidic bond types on antioxidant efficacy. Specifically, low-molecular-weight NSPs with high solubility and bioavailability often exhibit superior activity. Polysaccharides rich in glucose, galactose, or galacturonic acid demonstrate enhanced antioxidant effects, while diverse glycosidic bonds contribute to varied functional patterns through synergistic interactions with other structural features. This work provides a theoretical foundation for the precise application of NSPs in anti-diabetic therapeutics and functional foods. Future research should integrate multidimensional structural analysis, dynamic conformation monitoring, and artificial intelligence-assisted design to accelerate their clinical translation.