Comprehensive evaluation of walnut shell polysaccharides: isolation, purification, structural characterization, and therapeutic effects on type 2 diabetes via gut microbiota regulation.

Type 2 diabetes mellitus (T2DM) poses a significant global public health challenge with continuously rising incidence rates. Developing safe and effective hypoglycemic agents derived from natural products has become a current research focus. Walnut shells, as a vast agricultural and forestry waste material, hold substantial economic and environmental significance for high-value utilization. In this study, a polysaccharide (WSP-III) was isolated from walnut shells. This polysaccharide has an average molecular weight of 67.576 kDa and exhibits good thermal stability at 200 °C. Analysis of its monosaccharide composition, methylation profile, and nuclear magnetic resonance (NMR) spectroscopy revealed that its backbone of walnut shell polysaccharides consists of →1, 4-β-d-glucose and →1, 4-β-D-mannose, and →1, 4-β-D-galacturonic acid, with →1,4,6-β-D-galactose serving as the branching point, to which 1-α-L-arabinose and 1-α-D-xylose side chains are attached at the C-6 position. WSP-III significantly alleviates hyperglycemia in diabetic mice, regulates dyslipidemia, protects liver and kidney function, increases short-chain fatty acid content, and improves gut microbiota. This study provides preliminary insights into the structural characteristics and hypoglycemic activity of WSP-III, laying a theoretical foundation for further development of functional polysaccharides.