Evaluation Of Anti-alcoholic Liver Injury Activity Of Different Components Of Coriolus Versicolor Intracellular Polysaccharopeptide

Long-term excessive alcohol consumption induces alcoholic liver disease(ALD).ALD is a worldwide health problem,with significant morbidity and mortality.The polysaccharopeptides produced by Coriolus versicolor(PSK)is a kind of protein-bound polysaccharides.Anti-alcoholic liver injury activity of PKS,isolation and purification,and structure characterization of PSK-1b1 and PSK-1c1 has been studied in our laboratory.However,their activity against alcoholic liver injury has not been evaluated.Therefore,this study evaluated the anti-alcoholic liver injury activity of PSK-1b1 and PSK-1c1 in two mouse models of alcoholic liver injury,also explored the effects of PSK-1 on intestinal microbial community in ALD mice.The main results are as follows:(1)PSK-1b1 and PSK-1c1 were prepared from PSK-1 by using Hiprep DEAE FF column and Superdex 75 gel column.(2)The anti-alcoholic liver injury activity of PSK-1b1 and PSK-1c1 was evaluated in NIAAA mouse model.The results showed that: PSK-1b1 and PSK-1c1 significantly reduced the activity of serum ALT and AST;PSK-1b1 and PSK-1c1 improved the pathological conditions such as unclear lobular structure,inflammatory infiltration and steatosis caused by alcohol;PSK-1b1 and PSK-1c1 reduced lipid deposition in the liver by activating the AMPK pathway and PPAR?,inhibiting the expression of SREBP-1c and ACC1;PSK-1b1 and PSK-1c1 significantly decreased the production of ROS and oxidative stress through downregulating the expression of CYP2E1;PSK-1b1 and PSK-1c1 could significantly increase the expression of SOD and CAT in liver,improve the antioxidant levels in liver,and accelerate the clearance rate of oxygen free radicals;PSK-1b1 and PSK-1c1 could also downregulate TLR4-related pathways to regulate immune balance.In a word,PSK-1b1 and PSK-1c1 could prevent alcohol from damaging the liver.(3)In the acute alcoholic liver injury mouse model,PSK-1,PSK-1b1,and PSK-1c1 could reduce liver index;PSK-1,PSK-1b1,and PSK-1c1 significantly reduced ALT activity in mice serum,PSK-1 and PSK-1b1 reduced the activity of AST.PSK-1,PSK-1b1 and PSK-1c1 also significantly decreased the levels of TC and TG in mice serum;PSK-1,PSK-1b1,and PSK-1c1 improved alcohol-induced pathological conditions such as hepatic sinus enlargement,cell morphological deformation,inflammatory infiltration,and apoptosis;PSK-1,PSK-1b1 and PSK-1c1 increased the activity of CAT and SOD in liver tissue;PSK-1,PSK-1b1 and PSK-1c1 increased the expression of AMPK? and PPAR?,promoted the decomposition of fatty acids and inhibited the synthesis of lipids to reduce the deposition of hepatic lipids;PSK-1,PSK-1b1 and PSK-1c1 could inhibit the activity of CYP2E1,reduce the production of ROS,alcohol-induced oxidative stress,and lipid peroxidation;PSK-1,PSK-1b1 and PSK-1c1 could downregulate the expression of CD14,inhibit TLR4-related pathways,and regulate immune balance.In conclusion,PSK-1,PSK-1b1 and PSK-1c1 could prevent alcohol from damaging the liver.(4)There was a significant change in the intestinal microflora of mice after high-dose alcohol administration.PSK-1 could change the intestinal microbial community structure of mice,and reduce the influence of alcohol on the intestinal microflora in mice.