Nonalcoholic fatty liver disease (NAFLD) poses a great global challenge to public health, yet it holds promise for amelioration through plant-derived polysaccharide. Ginkgo biloba seeds have long been used as medicine and food, which has potential benefits for various chronic diseases. However, the protective role of Ginkgo biloba seed polysaccharide against NAFLD remains unclear. In this study, we isolated and purified polysaccharide (GBSP-2) from Ginkgo biloba seeds. GBSP-2 is composed of α-d-glucopyranose residues, which are interconnected with α-d-glucopyranose units linked by (1→4) bonds, (1→4,6) bonds and (1→3,4) bonds, the ratio distribution is 15:1:1. By studying a mouse model, we investigated the effect of GBSP-2 (100 or 200 mg/kg) on high-fat-diet-induced NAFLD. We demonstrated that GBSP-2 significantly alleviated NAFLD, as evidenced by reduced hepatic steatosis, decreased inflammation, improved oxidative stress and ameliorative glucolipid metabolic disorders. Furthermore, GBSP-2 mitigated gut microbiota disturbance of NAFLD mice and markedly increased the abundance of Akkermansia, Romboutsia, Lactobacillus and Bacteroides. Mechanistically, GBSP-2 could activate AMPK/ACC signaling pathway to inhibit lipid synthesis by generating 3,4-dihydroxyphenylpropionic acid (DHPPA). Overall, these findings suggest that GBSP-2 plays a multi-channel and multi-target role in improving NAFLD through the gut-liver axis.
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