In recent years, multiple edible polysaccharides from Codonopsis pilosula were mainly isolated with high average molecular weights and exhibited various bioactivities, but it was proven that low-molecular-weight polysaccharides could exert stronger activities due to the superior water solubility and permeability. In the present study, the water-soluble polysaccharide C. pilosula with low molecular weight was isolated under ultrasonic assistance at 30 °C, the extraction process was optimized via response surface method (RSM), and the structure and immunoregulatory activity were further investigated. The maximum yield (4.86%) for crude polysaccharides (cCPPs) was obtained under following parameters: ultrasonic power of 370 W, liquid/material ratio of 33 mL/g, ultrasonic time of 81 min. Subsequently, the cCPPs were further purified through dialysis and Sephadex G-25 column to acquire purified polysaccharide (CPPs). Structural analysis indicated that CPPs was a glucofructan (average molecular weight of 4.23 × 103 Da) with (2→1)-β-D-Fruf and (1→)-α-D-Glcp as the backbone branched by (2→6)-β-D-Fruf. Additionally, CPPs could enhance immunoregulatory function by stimulating NO production and cytokine (IL-6 and TNF-α) secretion of RAW264.7 macrophages dose-dependently, which presented no cytotoxic effects. These data suggest that CPPs have the potential to be used as a nutritional dietary compound and natural immunostimulant supplement in the food industry.
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