Hydrolysates exhibited differential modulatory effects on macrophage compared to the raw polysaccharide (xyloglucomannan) isolated from <i>Atractylodes macrocephala</i> Koidz

It has been claimed that <i>Atractylodes macrocephala</i> applied as a traditional Chinese medicinal herb for centuries, owing to its excellent immunomodulatory and hepatic protective properties. This study aims to explore the immunomodulation of oligosaccharides obtained by gastrointestinal digestion after oral administration of <i>A. macrocephala</i> polysaccharide (xyloglucomannan, XGM). The analysis of chemistry showed that XGM consisted of D-glucose, D-mannose, and D-xylose in a molar ratio of 6.8:3.0:1.0, and the molecular weight was 5465 Da. Furthermore, HCl and pancreatic amylase were used to simulate digestive tract hydrolysis of polysaccharides, obtaining two XGM hydrolysates (XGM-AH and -EH). Oligosaccharide identification results indicated that both XGM-AH and XGM-EH contained glucans (degree of polymerization, DP = 2 ∼ 5). XGM-AH had a wider variety of oligosaccharides than XGM-EH, mainly glucomannans. <i>In vitro</i> immunostimulatory assay indicated that XGM could effectively stimulate the activation and enhance the phagocytosis of RAW264.7 cells. In contrast, XGM-AH and -EH exhibited anti-inflammatory effects, inhibited lipopolysaccharide (LPS)-induced aberrant activation of macrophages, reduced the release of cytokines of macrophages. Flow cytometry assay suggested that XGM-AH and -EH inhibited LPS-induced M1-type polarization of macrophages. In conclusion, XGM-derived oligosaccharides possess anti-inflammatory bioactivities and exhibit differential macrophage regulatory behaviors in contrast to the immune-activating effects exhibited by the prototype polysaccharides.