A lymphatic route for a hyperbranched heteroglycan from Radix Astragali to trigger immune responses after oral dosing

Gut barrier makes a huge research gap between in vivo and in vitro studies of orally bioactive polysaccharides: whether/how they contact the related cells in vivo. A hyperbranched heteroglycan RAP from Radix Astragali, exerting antitumor and immunomodulatory effects in vitro and in vivo, is right an example. Here, we determined first that RAP's antitumor activity is immune-dependent. Being undegraded and non-absorbing, RAP quickly entered Peyer's patches (PPs) in 1 h where it directly targeted follicle dendritic cells and initiated antitumor immune responses. RAP was further delivered to mesenteric lymph node, bone marrow, and tumor. By contrast, the control Dendrobium officinale polysaccharide did not enter PPs. These findings revealed a blood/microbiotaindependent and selective lymphatic route for orally administrated RAP to directly contact immune cells and trigger antitumor immune responses. This route bridges the research gap between the in vitro and in vivo studies and might apply to many other bioactive polysaccharides.

Automated summary

The gut barrier poses a significant research challenge in studying orally bioactive polysaccharides in both in vivo and in vitro studies, particularly in understanding how these polysaccharides interact with related cells in vivo. This study examines the antitumor activity of a hyperbranched heteroglycan RAP from Radix Astragali, showing that its activity is immune-dependent and that it enters Peyer's patches to target dendritic cells and initiate antitumor immune responses. These findings provide insights into a lymphatic route for orally administered RAP to directly interact with immune cells and trigger antitumor immune responses, bridging the gap between in vitro and in vivo studies.