Study On The Effect And Mechanism Of Schisandra Chinensis Extract On Alcoholic Liver Disease In Mice

Alcoholic liver disease(ALD)is the most common form of chronic liver disease in the world.ALD encompasses a spectrum of phenotypes,generally progressing from alcoholic fatty liver to alcoholic hepatitis,even developing into liver fibrosis,cirrhosis,and eventually hepatocellular carcinoma.However,there continues to be a lack of safe and efficacious drugs for the prevention or treatment of ALD.Studies indicate the pathogenesis of ALD includes oxidative stress,cytokine-induced inflammation,destruction of the gut barrier,intestinal dysbiosis,etc.The intestinal microbiota has been considered as an extra organ of the human body.Under normal conditions,intestinal microbes maintain a dynamic balance and metabolize to produce various bioactive substances,which directly or indirectly affect the health of the host.Schisandra chinensis is a kind of berry,which is used as an herbal medicine for the treatment of liver diseases in traditional Chinese medicine.It is both a food and a medicine with good safety.The fruit of S.chinensis contains a variety of bioactive components,with anti-oxidation,anti-inflammation,liver protection,enhancing cardiovascular function,and bacteriostasis effects.Recent studies suggest that the regulation of intestinal microbiota may be one of the important mechanisms of traditional Chinese medicine in the treatment of diseases.The effect of S.chinensis in improving ALD and its mechanism mediated through intestinal microorganisms are still unclarified.This study aims to explore the effect and mechanism of S.chinensis extract in treating ALD and the role of intestinal microbes and metabolites in it.This study mainly includes the following research contents:1.Chemical composition analysis of S.chinensis extract.The chemical components of S.chinensis extract,detected by high performance liquid chromatography and ultra-high performance liquid chromatography q exactive mass spectrometry,mainly include phenols,flavonoids,terpenoids,lignans,phenylpropanoids,amino acid derivatives,alkaloids,and carbohydrates and derivatives.The literature record that these chemical components show anti-cancer,anti-oxidation,anti-inflammation,liver protection,and bacteriostasis effects.2.Study on the preventive effect of S.chinensis extract on ALD in mice.Based on the mouse model of chronic and binge ethanol feeding,the status of liver and intestine in mice was evaluated by methods of pathology and immunology,the composition of intestinal microbiota was analyzed using high-throughput sequencing,and intestinal metabolites were analyzed using proton nuclear magnetic resonance and high performance liquid chromatography.Schisandra chinensis extract improved liver injury and inflammation,regulated oxidative stress and nitrosative stress,and enhanced the small intestine barrier functions,including intestinal stem cells,intestinal peristalsis,and tight junctions.It improved the small intestinal and cecal dysbiosis,with the decreased proportion of microorganisms such as Escherichia-Shigella,Enterococcus,and Klebsiella and the increased proportion of probiotics such as Lactobacillus and Bifidobacterium.It also regulated the levels of amino acids,lactic acid,and short-chain fatty acids(SCFAs),which are metabolites of intestinal microorganisms.It was verified by in vitro bacterial growth test that S.chinensis extract selectively inhibited bacterial growth.3.Effect of intestinal dominant microbes enriched by S.chinensis extract on ALD.The dominant microbial samples of the small intestine and cecum of mice,which were enriched by S.chinensis extract,were prepared from in vitro gastrointestinal simulation system and healthy mice and were used for intestinal microbiota transplantation(IMT).IMT administration improved liver injury and inflammation and regulated oxidative stress and nitrosation stress.It improved the small intestinal and cecal dysbiosis,with the decreased proportion of Escherichia-Shigella and the increased proportion of SCFA producers,such as Lactobacillus,Bifidobacterium,Lachnospiraceae,and Ruminococcaceae.It was also observed that Enterococcus and Klebsiella increased in some IMT groups.IMT administration also regulated intestinal lactic acid and SCFA levels.These results indicated that intestinal microbiota played an assistant role in the treatment of ALD by S.chinensis extract.Although intestinal microbiota was more sensitive than cecal microbiota in the progression of the disease,transplantation of small intestinal samples and cecal samples had similar effects on improving ALD.4.Research on the key intestinal microbes of S.chinensis extract in improving ALD in mice.Klebsiella oxytoca,Enterococcus faecalis,Lactobacillus plantarum,and Bifidobacterium breve were respectively given to ALD mice,and the mixture of L.Plantarum and B.breve was given to ALD mice.The results showed that L.plantarum and B.breve improved liver injury and inflammation,regulated oxidative stress and nitrosation stress,enhanced intestinal function,and regulated intestinal microbiota and metabolites.Enterococcus faecalis and K.oxytoca played a partially beneficial role in ALD mice.Inhibiting the growth of Escherichia-Shigella and increasing the proportion of SCFAs producers,such as Lactobacillus and Bifidobacterium,maybe the key microbial changes of S.chinensis extract in improving ALD.The controversial effects of E.faecalis and K.oxytoca remain to be further investigated.In conclusion,Schisandra chinensis extract effectively improved ALD,regulated the composition of intestinal microbiota and the level of metabolites,and changes in intestinal microbiota are directly related to the improvement of ALD.EscherichiaShigella and SCFAs producers,such as Lactobacillus and Bifidobacterium,maybe the key microorganisms in the improvement of ALD by S.chinensis extract.This study provides a valuable reference for the clinical use of S.chinensis to prevent or treat ALD,a new idea for the management of donor samples in fecal microbiota transplantation,and a new range of options for the therapeutic strategies with the use of microorganisms to modulate the intestinal microbiota.