BG-136

We studied the mechanisms underlying the immunostimulatory effects of aβ-1,3/1,6-glucan (BG136) from Durvillaea Antarctica. Our data showed that BG136 promoted the activation of MAPKs and NF-κB signaling pathways and cytokines production. BG136 did not increase MCP-1 or NO production or phosphorylation of NF-κB and MAPK in TLR4 siRNA knockdown cells, indicating that BG136 activates macrophages through TLR4. Flow cytometry analysis and confocal experiment showed that BG136 bound to TLR4 expressed on RAW264.7 macrophage cells surface. The affinity of BG136 for TLR4 was determined using Surface Plasmon Resonance (SPR) (KD: 4.51 × 10^-6M). Altogether, our results showed that BG136 activates RAW264.7 cells by binding to TLR4 and then triggering TLR4-mediated signaling pathways to promote cytokines secretion.

BG136, a β-1,3/1,6-glucan derived from Durvillaea antarctica, is an injectable anticancer drug and has entered Phase II clinical trials. Rational oral formulation design is a pivotal focus for our future drug development research; therefore, elucidating the gastrointestinal fate of BG136 becomes imperative. This study investigated the stability and biotransformation of BG136 via in vitro digestion and gut microbiota fermentation. The results confirmed BG136’s structural integrity, resistance to degradation in a highly acid environment and by gastrointestinal tract enzymes. In contrast, BG136 was degraded by intestinal bacteria into mid-size fragments along with smaller oligosaccharides. Additionally, the biotransformation process notably elevated total short-chain fatty acids (SCFAs) to 38.37 ± 3.29 mM, representing a 59.4% increase versus controls (24.08 ± 2.29 mM), with propionic acid exhibiting the most substantial increase. Meanwhile, the process was accompanied by significant microbial regulation, including an increase in beneficial genera (Lactobacillus, Enterococcus) and a reduction in Lachnoclostridium populations. Overall, these findings systematically map the oral bioavailability challenges and prebiotic potential of BG136, highlighting its microbiota-modulating capacity through species-specific ecological regulation, providing insights into oral drug development for BG136.