Structural characterization and anti-tumor immunomodulatory effects of polysaccharides from Astragalus mongholicus with different cultivation modes.

Cultivation modes can significantly influence the pharmacological properties of Astragalus mongholicus Bunge. However, the differences in its polysaccharides, key bioactive components, have not been systematically explored. Two neutral homogeneous polysaccharides, APS-I (120 kDa) and APS-II (12 kDa), were isolated from different cultivars and characterized. Structural analysis revealed that both are heteropolysaccharides with high glucose content (>90 %), but APS-II exhibits a highly branched structure with a compact, spherical conformation, while APS-I has a less branched, more extended, chain-like form. In vitro, both polysaccharides promoted polarization of M0-type macrophages to the M1-type and repolarized M2-type to M1-type. Notably, APS-II exhibited superior efficacy compared to APS-I at the same dosage. Mechanistic studies indicated that APS-II exerts its effects via the TLR4-MyD88-NF-κB signaling pathway. In vivo, using the 4 T1 orthotopic tumor model, APS-II preferentially accumulated at tumor sites, enhancing the innate immune system's antitumor capacity and significantly improving cyclophosphamide's antitumor efficacy while alleviating its immunosuppressive toxicity. In summary, our findings indicate that the wild-simulated cultivation mode leads to the production of a novel polysaccharide component, APS-II, which has not been previously reported. This polysaccharide plays a key role in anti-tumor immunotherapy and shows potential to enhance conventional cancer treatments when combined with chemotherapy.