Polysaccharides from Cistanche deserticola Ma prevent alcoholic fatty liver disease by regulating hepatic lipid metabolism and gut microbiota in mice.

Cistanche deserticola Ma polysaccharide (CDP) is an active ingredient extracted from Cistanche deserticola Ma (CD) and is believed to have hepatoprotective activity. However, the molecular mechanism of its hepatoprotective effect by intervening in alcoholic fatty liver disease (AFLD) remains unclear. In the present study, three polysaccharides were isolated and purified from CD, and the polysaccharide with the better lipid-lowering and liver-protecting activity and the highest yield, CDPS, was selected by in vitro experiments for subsequent. The efficacy of CDPS in ameliorating AFLD in mice was evaluated using hepatic lipidomics, 16S rRNA analysis and molecular biology experiments. The present study showed that CDPS significantly improved alcohol-induced weight loss, lipid accumulation, ALT, AST, inflammation and dyslipidemia, suggesting that CDPS can prevent AFLD. Lipidomics showed that CDPS improved lipid metabolism disorders by regulating glycerophospholipid metabolism, linoleic acid metabolism, and arachidonic acid metabolism. 16S rRNA analysis showed that CDPS ameliorated alcohol-induced gut microbiota disruption. In particular, CDPS supplementation reduced the abundance of Bacteroides, Parabacteroides, and Escherichia-Shigella and increased the abundance of Ruminococcaceae_UCG-010, Lachnospiraceae_NK4A136_group and Faecalibaculum abundance, and promoted the production of SCFAs. We further used Western blotting to determine the levels of proteins involved in lipogenesis and catabolism, and CDPS intervention resulted in decreased levels of lipid synthesis-associated proteins (SREBP-1c and FAS) and increased levels of lipid catabolism-associated proteins (PPARα) and p-AMPK/AMPK ratio. Our results suggest that CDPS has the potential to prevent AFLD by modulating lipid metabolism, altering the gut microbiota, increasing the content of SCFAs, activating the AMPK signaling pathway to promote fatty acid β-oxidation and limiting fatty acid biosynthesis, which provides a basis for further development of therapeutic drugs for AFLD.