Acidic polysaccharides from Cistanche deserticola and their effects on the polarization of tumor-associated macrophages.

Three purified polysaccharides, CDAP-1, CDAP-2, and CDAP-3, were prepared from the rhizome of Cistanche deserticola and characterized. Structural analysis revealed that CDAP-1 and CDAP-2 are highly branched RG-I-type polysaccharides with side chains, including arabinans, galactans, and/or AGs, whereas CDAP-3 is a typical HG-type polysaccharide. In vivo tests revealed that treatment with the crude polysaccharide fraction (CDCP) significantly prolonged the survival of H22 tumor-bearing mice and exhibited antitumor effects. In vitro experiments demonstrated that all three polysaccharides could polarize M2-like TAMs toward the M1 phenotype. As a major component of CDCP, CDAP-2 could act on M2 macrophages through the TLR4 receptor-mediated NF-κB signaling pathway. An in vitro cell model verified that CDAP-2 could inhibit cell proliferation by reversing the polarization of M2-like TAMs to the cytotoxic M1 phenotype. Overall, we found that CDCP showed a clear antitumor effect and that its major component, CDAP-2, could reverse the suppressive TAM phenotype in the microenvironment, providing a scientific basis for the clinical application and development of C. deserticola.