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

• Published in: International journal of biological macromolecules 2024-12, Vol.282 (Pt 4), p.137207, Article 137207
• Main Authors: Jiang, Siliang, Cui, Yongsheng, Wang, Bo, Fu, Zheng, Dong, Caixia
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Cell Proliferation - drug effects; Cistanche - chemistry; Cistanche deserticola; Humans; Mice; NF-kappa B - metabolism; Polysaccharide; Polysaccharides - chemistry; Polysaccharides - pharmacology; RAW 264.7 Cells; Signal Transduction - drug effects; TLR4–NF-κB; Toll-Like Receptor 4 - metabolism; Tumor-associated macrophages; Tumor-Associated Macrophages - drug effects; Tumor-Associated Macrophages - metabolism
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.137207

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. •Three acidic polysaccharides were isolated from CDCP of Cistanche deserticola.•Structure of three polysaccharides was characterized.•Treatment with CDCP significantly prolonged the survival of H22 tumor-bearing mice.•Three polysaccharides could polarize M2-like TAMs toward the M1 phenotype.•CDAP-2 could reverse the suppressive TAMs through TLR4-NF-κB signaling pathway.