Polysaccharides as the Key Differentiator in Raw and Processed Pinellia ternata Tubers: Immunostimulatory Effects and Mechanism of Action.

Raw tubers of Pinellia ternata (PTRs) and processed ones (PTPs) have varied therapeutic applications in traditional medicine. PTRs are used to treat cancer, whereas PTPs are used to treat coughing and phlegm. The underlying reason for this difference is still unknown. This study aimed to investigate whether polysaccharides are the key differentiators in the traditional uses of PTRs and PTPs and to explore the possible mechanism for the immunomodulatory effects of polysaccharides from PTRs. PTRs and PTPs were used to produce the total polysaccharides PTR.PS and PTP.PS, respectively, which were physiochemically characterized using various techniques, such as gel permeation chromatography, nuclear magnetic resonance spectroscopy and high-performance liquid chromatography. Their immunomodulatory activity was evaluated by flow cytometry analysis in bone marrow-derived macrophages (BMDMs) and bone marrow-derived dendritic cells (BMDCs) for the analyses of activation markers and concentrations of cytokines secreted. The mechanistic study was elucidated by Western blot analysis. Physicochemical characterization revealed that PTR.PS had lower molecular weights and greater abundance of monosaccharide components, including mannose and galacturonic acid, than PTP.PS. The bioactivity analysis result showed that PTR.PS has robust immunostimulatory effects on BMDMs and BMDCs by the upregulation of NF-κB and mitogen-activated protein kinase (MAPK) pathways leading to the increased expression of activation markers and cytokine secretion. The proinflammatory M1 macrophages induce an inflammatory condition, and the activated dendritic cells can activate T cells for a cell-mediated adaptive immune response. Polysaccharides are the key difference between PTRs and PTPs, resulting in different immunostimulatory effects, which are regulated through NF-κB and MAPK pathways.