Polysaccharides from Cistanche deserticola: A Comparative Study of the Impacts of the Extraction Methods on Yield, Structure, Physicochemical Properties, Antioxidant, and Hypolipidemic Activities

Polysaccharides from wine-processed Cistanche deserticola Y.C. Ma (WCPs) are gaining increasing interest because of their diverse bioactivities, yet the extraction method critically affects polysaccharide yield, structure, and function. This study was designed to systematically compare seven extraction strategies and establish a clear method–structure–activity relationship for obtaining high-quality WCPs. Seven extraction protocols, hot water (HWE), enzymatic-assisted (EAE), ultrasound-assisted (UAE), ultrasound–microwave synergistic (UMSE), microwave-assisted (MAE), ultrasound–enzyme combined (UESE), and natural deep-eutectic-solvent (NADES-E) extraction, were evaluated in parallel. UV, FT-IR, Congo-red assays, monosaccharide composition, molecular-weight distribution, and SEM were employed to characterize the functional groups and surface ultrastructures of the obtained WCPs. Five deproteinization techniques were also screened for maximal protein removal with minimal polysaccharide loss. Antioxidant (DPPH, ABTS⁺, OH scavenging) and lipid-lowering (sodium cholate, glycodeoxycholate, taurodeoxycholate binding) activities were measured in a concentration-dependent manner. Optimal extraction conditions were determined to maximize polysaccharide yield and activity. HWE achieved the highest polysaccharide yield (28.43 ± 0.61%), significantly higher than other extraction methods (p < 0.05). Structural and structure–activity relationship analyses demonstrated that the increased bioactivity was driven by specific structural alterations resulting from the extraction process. These alterations notably included increases in the total phenolics and uronic acids, as well as changes in monosaccharide composition, particularly increased levels of mannose and galacturonic acid. The extracted polysaccharides therefore showed markedly greater efficacy in both antioxidant and lipid-lowering activity assays. Among the protein removal methods evaluated, the Sevage method was determined to be the most suitable, as it effectively removed proteins while best preserving polysaccharide bioactivity. Quantitative associations among the WCP extraction protocol, structural composition, and bioactivity were established. HWE is recommended as a simple, high-yield route to produce highly active WCPs for functional-food and pharmaceutical development. These findings provide valuable insights into the structure–activity relationships of WCPs and their potential in functional food development.