Oyster (Crassostrea gigas) Polysaccharide Ameliorates High-Fat-Diet-Induced Oxidative Stress and Inflammation in the Liver via the Bile Acid-FXR-AMPKα Pathway.

Abstract

Oyster polysaccharides (OPS) have a variety of biological activities. In this study, we aimed to investigate the potential mechanisms of OPS to ameliorate hepatic oxidative stress and inflammation in mice induced by a high-fat diet (HFD). The results showed that OPS reduced the HFD-induced increases in serum transaminase levels and alleviated hepatic oxidative stress and inflammation. Moreover, OPS regulated bile acid metabolism and increased bile acid content in the liver, serum, and feces. Serum bile acid profile results indicated that OPS reduced levels of chenodeoxycholic acid, deoxycholic acid, and lithocholic acid associated with high-affinity agonists of Farnesol X receptor (FXR). Western blot analysis showed that OPS accelerated bile acid metabolism by downregulating hepatic FXR expression and promoting its downstream CYP7A1, CYP27A1, and CYP8B1 protein expression. Meanwhile, OPS ameliorated oxidative stress and inflammation in the liver by modulating FXR-AMPKα-Nrf2/NF-κB signaling to reduce p-IκBα/IκBα, p-NF-κB p65/NF-κB p65, IL-1β, and TNF-α expression and increase p-Nrf2/Nrf2, HO-1, and NQO-1 expression. This study was the first to explore the possible mechanism of OPS in improving liver oxidative stress and inflammation from the perspective of bile acid metabolism, providing a theoretical basis for OPS as a new source of functional food.