Structural Characterization and Hepatoprotective Effects of Tibetan Gastrodia elata Blume Polysaccharide ZGE-2 Against Alcoholic Liver Injury

Gastrodia elata Blume (G. elata), a traditional Chinese medicinal herb with neuroregulatory and cognition-enhancing properties, has recently attracted attention for its hepatoprotective properties. Through sequential purification involving ultrasonic extraction, Sevag deproteinization, and chromatographic separation (DEAE cellulose-52 and Sephadex G-75), a homogeneous polysaccharide (ZGE-2) was isolated from Tibetan G. elata, exhibiting a peak molecular weight of 19.337 kDa with exclusive glucose composition. Methylation-GC-MS analysis indicated one non-reducing terminal Glcp-(1 → residue, linear → 4)-Glcp-(1 → and → 6)-Glcp-(1 → residues, as well as branch-point → 3,4)-Glcp-(1 → and → 4,6)-Glcp-(1 → residues in ZGE-2. In the zebrafish in vivo model, ZGE-2 treatment not only ameliorated lipid metabolism disorders by reducing hepatic triglycerides (TG) and total cholesterol (TC) levels but also enhanced antioxidant capacity through SOD activation and suppression of MDA accumulation by attenuating oxidative stress via the Nrf2/HO-1 pathway and modulated alcohol metabolism pathways by downregulating ADH and ALDH expression. Furthermore, ZGE-2 treatment also had the potential to inhibit the production of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). At the transcriptional level, ZGE-2 downregulated oxidative stress-related genes (Nrf2 and HO-1), suppressed pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and reduced the relative mRNA expression of alcohol metabolism-related genes (ADH and ALDH). Collectively, these findings indicate that G. elata polysaccharides mitigate alcohol-induced hepatic and systemic injury and improve lipid homeostasis via antioxidant, anti-inflammatory, and metabolic modulation, supporting their potential as hepatoprotective agents.