Structural elucidation of an active arabinoglucan from Gomphrena globosa and its protection effect and mechanism against metabolic dysfunction-associated steatohepatitis

The flower of Gomphrena globosa (G. globosa.) is used as Chinese traditional medicine and functional food. Extractions from G. globosa. have been reported to exert hepatoprotective effects. We further hypothesized that the polysaccharide components, as a bioactive ingredient, might have anti-fatty and hepatitis function. Here, a novel homogeneous arabinoglucan GGL0.05S1 (Mw = 83.9 kDa) from this flower, was characterized by monosaccharide composition analysis, methylation analysis, and NMR. Structural analysis showed that the backbone of GGL0.05S1 consists of →4)-α-Glcp-(1→ and →4,6)-α-Glcp-(1→ residues, and the branched chain linked to the main chain via C-6 of →4,6)-α-Glcp-(1→ in the form α-Araf-(1→[4)-α-Glcp-(1]_b→ (b > 2). In vitro experiments demonstrated that GGL0.05S1 could inhibit lipid deposition and ROS overload in free fatty acid-induced hepatocytes, meanwhile in vivo tests showed that GGL0.05S1 effectively protected against liver injury, steatohepatitis, and fibrosis in a CDA-HFD-fed MASH model. Mechanism study further uncovered that GGL0.05S1 augmented the expression and antioxidant ability of thioredoxin protein that ameliorated oxidative stress, promoted fatty acid β-oxidation and mitophagy, up to reducing lipotoxicity and alleviating inflammation via inhibiting NLRP3 signaling pathway. Overall, GGL0.05S1 might be a potential novel active compound with liver-protective effect from G. globosa., and which is informative for anti-MASH new drug development.