Structural characterization of a novel comb-like branched α-D-glucan from Arca inflata and its immunoregulatory activities in vitro and in vivo
In the current study, we identified and characterized a novel water-soluble polysaccharide (JNY2PW) with significant immunoregulatory effects with no observable overall toxicity. Isolated from Arca inflata, JNY2PW belongs to a novel class of α-glucan with a molecular weight of 5.25 × 107 Da. The backbone composed of (1→4)-linked α-D-glucopyranosyl residues and a single (1→6)-α-D-glucopyranosyl branched unit for every five α-D-glucopyranosyl residues, showing a comb-like α-D-glucan with intensive short branches. In in vitro models, We demonstrated that JNY2PW exerted significantly immunoregulatory effects by promoting the production of nitric oxide, interleukin-6, and tumor necrosis factor α. The pathway involved activation of the TLR4-MAPK/NF-κB signaling cassette in murine RAW264.7 macrophages. In an in vivo immunosuppressive mice models induced by cyclophosphamide treatment, we found that JNY2PW treatment produced good antitumor activity comparable with chemotherapy by doxycycline in murine breast carcinoma 4T1-bearing mice, but devoid of any observable side effects (e.g. losing weight) related with doxycycline treatment. The anti-tumor mechanism of JNY2PW may involve overall enhanced mice’s immune responses to tumors. These results indicate that JNY2PW possess the potential utilities as adjunctives to existing chemotherapy or current immune-oncology treatment.