Pharmacodynamic Re-evaluation And Mechanism Of Mori Fructus Polysaccharide MFPA1 And MFPB1 Against Acute Alcoholic Liver Injury

Alcoholic liver disease(ALD)is a liver disease caused by excessive alcohol intake and is one of the liver diseases with the highest mortality in the world.However,in the drug market,there is no specific treatment for ALD except anti-hepatitis virus drugs.Therefore,finding and using high-efficiency active ingredients is a hot spot of current research.Mori Fructus polysaccharide(MFP)is a type of polysaccharide extracted and purified from Mori Fructus.Studies have shown that it has many biological activities such as anti-oxidation,hypoglycemia,immune regulation,and anti-liver injury,but the anti-acute alcoholic liver injury mechanism of MFP has not been clearly elucidated,therefore MFP has value and significance as a potential anti-liver injury drug for indepth study.In the early stage,our group conducted a lot of basic research work on the evaluation of the efficacy of MFP against acute alcoholic liver injury,and clarified its bioactive fractions against acute alcoholic liver injury.It was characterized and molecularly modified,and its anti-oxidant,anti-chemical liver injury and anti-alcoholic liver injury activities were preliminarily determined.On this basis,this work selected two MFPs with the best anti-alcoholic liver injury activity,MFPA1 and MFPB1,to study their anti-acute alcoholic liver injury mechanisms.In this study,a mouse model of acute alcoholic liver injury was established,and the pharmacodynamics of MFPA1 and MFPB1 were re-evaluated.All the mice was evaluated from the perspective of oxidative stress and lipid metabolism.In order to fully and specifically elucidate the mechanism of MFP’s anti-alcoholic liver injury,we discussed the different lipids and lipid metabolism pathways of MFP.The main content and results are as follows:1.60 SPF male mice were randomly divided into five groups,normal control group,model group,bifendate group,MFPA1 group,MFPB1 group.A mouse model of acute alcoholic liver injury was established,and the efficacy of MFP was re-evaluated from three aspects: physiological and biochemical index detection,morphological observation,and histopathological observation.The results are as follows: The weight of mice with acute alcoholic liver injury decreased slightly,the liver index increased,and obvious physiological and biochemical index disorders appeared.Hispathological observation showed swelling,vacuolation,and necrosis of liver cells.Compared with the model group,the levels of serum ALT,AST,and TG in the bifendate group and the MFP group were significantly lower.Hispathological observations showed that the liver cells were intact in structure and clear in shape.The above results show that the model is successfully induced,and the MFPA1 and MFPB1 have good hepatoprotective effects.2.The oxidative stress levels of five groups of mice were investigated based on traditional oxidative stress targets,and biological explanations were made in conjunction with oxidative stress signaling pathways.The results showed that the MFPA1 and MFPB1 groups had significantly increased liver SOD content,and significantly decreased MDA levels.According to multivariate statistical analysis,the model group had a significant tendency to separate from the other four groups,and the other four groups had no separation.It shows that MFP components MFPA1 and MFPB1 can effectively inhibit the oxidative stress level of alcoholic liver injury.3.Using the lipidomics method based on high-resolution quadrupole orbitrap mass spectrometry,the lipids disorders in acute alcoholic liver injury were identified,the effect of MFP on the improvement of abnormal lipid metabolism was clarified.The results of liver lipidomics showed that acute alcoholic liver injury caused liver metabolic disorders in mice.There was a significant difference in the content of 10 lipids in the livers of the normal control group and the model group.MFP improved 4lipids in the liver.Analysis of the metabolic pathways of the above four lipids showed that MFP may play an anti-acute alcoholic liver injury effect by interfering with the metabolism of linoleic acid,α-linolenic acid and glycerophospholipids.This work provides important scientific basis and application value for MFP as a potential drug for the treatment of acute alcoholic liver injury.