Polysaccharide from Asparagus officinalis activated macrophages through NLRP3 inflammasome based on RNA-seq analysis

Abstract

Some polysaccharides with established medical and nutritional values have been identified to possess immunomodulatory properties devoid of any toxic or adverse effects. Previous studies have demonstrated that water-soaked polysaccharides from the skin of white asparagus can enhance cytokine release in RAW 264.7 macrophages, however, the underlying mechanism governing immune regulation remains elusive. In this study, we obtained a lower molecular weight polysaccharide (AP) through acid extraction, with an average MW of approximately 9.5 kDa. SEM and AFM spectroscopy analysis revealed well-dispersed spherical particle with triple helix conformation for AP, characterized by intertwined branching structures. Treatment with AP resulted in a time-dependent increase in nitric oxide levels and cytokine production in both RAW 264.7 cells and primary peritoneal macrophages. RNA-seq analysis indicated that AP activated macrophages via NLRP3 inflammasome signaling pathway. Furthermore, AP activated MAPKs and JAK/STAT signaling pathways to amplify the inflammatory response. Additionally, administration of AP improved visceral index and reduced inflammatory cell counts in CYP-induced immunosuppressed mice models. These findings suggest that AP holds potential as an immuno-enhancement mediator, wherein MAPK and JAK/STAT3 signaling pathways play a role in NLRP3 inflammasome activation of macrophages. • The triple helix conformation with large ‘pores’ on the surface of AP facilitated the interaction with cells. • AP increased the levels of NO and cytokines in macrophages. • AP activated NLRP3 inflammasome by regulating many pathways related to immunity and inflammation. • AP as an immuno-enhancement mediator, improved visceral index and reduced inflammatory cell counts of immunosuppressed mice.

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