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 foodTremella aurantialba, remain poorly understood in both structure and function. Herein, we describe a novel heteropolysaccharide, designated TAP-2a, isolated from the fruiting bodies ofT. aurantialbavia multi-step column chromatography. With a molecular weight of 16.95 kDa, TAP-2a is dominated by the pyranose forms of ᴅ-galactose (ᴅ-Galp), ᴅ-glucose (ᴅ-Glcp) and ᴅ-mannose (ᴅ-Manp), accompanied by minor proportions of ᴅ-xylose (ᴅ-Xylp), ʟ-fucose (ʟ-Fucp) and glucuronic acid. Methylation-GC-MS and exhaustive 1D/2D NMR analyses revealed a backbone assembled from →6)-α-Galp-(1→, →6)-β-Glcp-(1→, and →3)-α-Manp-(1→residues, branched at →2,6)-β-Galp-(1→, →3,6)-α-Galp-(1→, and →2,3)-α-Manp-(1→residues, and terminated by β-Glcp-(1→, α-Fucp-(1→, and β-Xylp-(1→. This intricate glycosidic architecture generates an exceptionally complex mannoglucogalactan in which a Gal→Man domain is substituted atO-3 of Gal by t-β-Glcpside chains and atO-2 of Man by t-α-Fucpstubs; additionally, a discrete fragment comprising t-β-Glcp-(1→3)-β-Glcp-(1→ was identified, along with a minor branch in which t-β-Xylpis attached toO-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 ofT. aurantialbaas powerful immunomodulators that underpin the fungus’s renowned medicinal efficacy.