Structural Characterization and Immunomodulatory Activity of a Novel Mannoglucogalactan from Tremella aurantialba: Implications for Natural Immunotherapy

Heteropolysaccharides, the principal bioactive constituents of the esteemed medicinal food <i>Tremella aurantialba</i>, remain poorly understood in both structure and function. Herein, we describe a novel heteropolysaccharide, designated TAP-2a, isolated from the fruiting bodies of <i>T. aurantialba</i> via multi-step column chromatography. With a molecular weight of 16.95 kDa, TAP-2a is dominated by the pyranose forms of ᴅ-galactose (ᴅ-Gal<i>p</i>), ᴅ-glucose (ᴅ-Glc<i>p</i>) and ᴅ-mannose (ᴅ-Man<i>p</i>), accompanied by minor proportions of ᴅ-xylose (ᴅ-Xyl<i>p</i>), ʟ-fucose (ʟ-Fuc<i>p</i>) and glucuronic acid. Methylation-GC-MS and exhaustive 1D/2D NMR analyses revealed a backbone assembled from →6)-α-Gal<i>p</i>-(1→, →6)-β-Glc<i>p</i>-(1→, and →3)-α-Man<i>p</i>-(1→residues, branched at →2,6)-β-Gal<i>p</i>-(1→, →3,6)-α-Gal<i>p</i>-(1→, and →2,3)-α-Man<i>p</i>-(1→residues, and terminated by β-Glc<i>p</i>-(1→, α-Fuc<i>p</i>-(1→, and β-Xyl<i>p</i>-(1→. This intricate glycosidic architecture generates an exceptionally complex mannoglucogalactan in which a Gal→Man domain is substituted at <i>O</i>-3 of Gal by t-β-Glc<i>p</i> side chains and at <i>O</i>-2 of Man by t-α-Fuc<i>p</i> stubs; additionally, a discrete fragment comprising t-β-Glc<i>p</i>-(1→3)-β-Glc<i>p</i>-(1→ was identified, along with a minor branch in which t-β-Xyl<i>p</i> is attached to <i>O</i>-2 of a mannose residue. Functionally, TAP-2a proved to be a potent immunomodulator, markedly enhancing the secretion of nitric oxide, interleukin-1β, interleukin-6 and tumour necrosis factor-α while concurrently up-regulating the corresponding mRNA transcripts and augmenting phagocytic capacity. These findings establish the highly elaborate heteropolysaccharides of <i>T. aurantialba</i> as powerful immunomodulators that underpin the fungus's renowned medicinal efficacy.