Structure characteristics of a novel pectic polysaccharide from Fructus Corni and its protective effect on alcoholic fatty liver

Alcoholic fatty liver disease (AFLD) is characterized by the accumulation of hepatic lipid and has no effective treatment yet. Fructus Corni is a traditional Chinese medicinal herb, and its extractions have demonstrated hepatoprotective properties. We hypothesize that the polysaccharides in Fructus Corni might have therapeutic effects on AFLD. In this study, we isolated a novel homogeneous polysaccharide, APFC-2 (Mw= 63.0 kDa), from the Fructus Corni, and its structure was elucidated by monosaccharide composition, methylation analysis, partial acid hydrolysis, and NMR spectra. APFC-2 is a pectic polysaccharide characterized by a backbone of T-β-Galp-(1 → 6)-β-Galp-(1 → 3,6)-β-Galp-(1 → [4)-α-GalpA-OMe-(1 → 4)-α-GalpA-(1→]_m → [2,4)-α-Rhap-(1 → 4)-α-GalpA-(1→]_n, with branches comprising T-Araf-(1→, →3)-α-Araf-(1→, →3,5)-α-Araf-(1→, and →5)-α-Araf-(1→. In vivo experiments indicated that APFC-2 could significantly reduce hepatic steatosis, fasting triglyceride, and cholesterol levels in AFLD mice. Cell proliferation and Oil Red O staining results showed that APFC-2 concentration-dependently increased cell viability and significantly improved lipid metabolism in vitro. Mechanistically, APFC-2 markedly inhibited the formation of lipid both in vitro and in vivo through activating liver kinase B1 (LKB1) and then regulating adenosine 5'-monophosphate-activated protein kinase (AMPK)-SREBP-1 and AMPK-PPAR-α pathways. This research provides a theoretical basis for the potential application of Fructus Corni pectic polysaccharide as a specific activator of LKB1 for treating AFLD.