Purified arabinogalactan from Gum Arabic demonstrated immunomodulatory effects by producing GM-CSF and reducing IL-17A levels in RAW 264.7 macrophages

Gum Arabic is a commonly used emulsifier and stabilizer that, when acting synergistically with IFN-γ, enhances pro-inflammatory responses in macrophages. This study aimed to determine if this activity derives from its primary polysaccharide component, arabinogalactan, and to examine how polysaccharide structure (core vs. side chain) influences this activity. We used the Smith degradation method to purify arabinogalactan from Gum Arabic. This process removed most side chains and drastically reduced protein content (from 131.85 to 1.36 μg/mL). Key findings showed that the purified arabinogalactan, after Smith degradation, had markedly different immunomodulatory properties compared to unpurified Gum Arabic. Purified arabinogalactan with IFN-γ did not induce nitric oxide nor significantly affect reactive oxygen species production. Nonetheless, a new observation was the induction of GM-CSF (2.3-fold increase) in the RAW 264.7 cells, which subsequently led to elevated TNF-α and IL-6, while significantly decreasing IL-10.In stark contrast to Gum Arabic, which induced a > 10-fold increase in IL-17, the purified arabinogalactan core failed to stimulate IL-17 production. This abrogation correlated with reduced downstream TNF-α and IL-6, and the complete absence of IL-1β. Purified arabinogalactan promotes a more balanced M1/M2 phenotype, rather than the intense M1 polarization seen with Gum Arabic. This study suggests that the high pro-inflammatory activity of Gum Arabic (including NO and IL-17 induction) is likely attributable to protein impurities or to the intact side-chain structure, rather than the arabinogalactan polysaccharide core itself. Therefore, the purity of arabinogalactan is essential for its immunomodulatory function.