Immunomodulatory Properties of an Arabinan Polysaccharide Extracted from Sida Cordifolia: Isolation, Characterization and in Vitro Mechanism of Action

An arabinan polysaccharide of low molecular weight (SC-S50, 3.2 KDa) and a structurally-related high molecular weight arabinan (SC-P50, 66 KDa) were isolated from Sida cordifolia root. NMR spectroscopy revealed the two polysaccharides were structurally similar consisting of three motifs, the main one being an α-L-arabinofuranose disaccharide (A-(1 → 5)-D) in the linear backbone; the A unit is further substituted at O-2 and O-3 positions by α-L-arabinofuranose. The two minority motifs also consist of α-1 → 5 linked L-arabinofuranose disaccharide, but in contrast, the A unit is replaced by the E or F unit, which is substituted by α-L-arabinofuranose only at the O-2 or O-3 position. SC-S50 did not activate macrophages cells in vitro, but in contrast, SC-P50 potently stimulated nitric oxide production in RAW264.7 macrophages (EC50: 7.92 μg/mL). SC-P50 significantly increased pinocytosis (phagocytosis), cell proliferation and cytokine secretion (IL-2, IL-6, TNF-α, IL-8), with minimal cytotoxicity. SC-P50 was then screened in 12 human primary cell-systems simulating various human tissue and disease characteristics. In 10 of these cell systems SC-P50 increased the production of IL-8. Mechanism-of-action studies unpicked the receptors, intracellular signalling and metabolic responses underlying SC-P50's immunomodulatory actions. SC-P50 is a novel immunomodulatory plant-derived polysaccharide which should be evaluated for its ability to prevent/treat infection.