| Background and purpose of the studyWith the prevalence of metabolic diseases,the incidence of nonalcoholic fatty liver disease(NAFLD)continues to rise.The incidence of NAFLD is closely related to living habits.Early detection of NAFLD can effectively reduce the incidence and mortality of liver fibrosis and liver cancer,and reduce the medical burden on society and patients.Drugs commonly used in the clinical treatment of NAFLD have side effects such as liver and kidney injury and increase the risk of cardiovascular disease.It is urgent to find efficient and safe drugs for the treatment of NAFLD.Highland barley Monascus purpureus Went.is a new type of Tibetan medicine fermented by Monascus with highland barley grains as substrate.Both highland barley Monascus purpureus Went.and red yeast rice are medicinal and edible medicinal materials,mainly containing statins such as lovastatin,and highland barley Monascus purpureus Went.also contains β-glucan with lipid-lowering and gastrointestinal protection.Previous studies have shown that highland barley Monascus purpureus Went.lipid-lowering effect is better than red yeast rice.Hyperlipidemia is an important factor in the pathogenesis of NAFLD.Because of this,in this study,the pharmacodynamics,metabolomics,and mechanism of action of highland barley Monascus purpureus Went.against the nonalcoholic fatty liver disease were discussed,providing a basis for the clinical application and new drug development of highland barley Monascus purpureus Went.against nonalcoholic fatty liver disease.Methods and results1.Efficacy evaluation of highland barley Monascus purpureus Went.on nonalcoholic fatty liver diseaseThe golden hamster model of nonalcoholic fatty liver disease was induced by feeding high-fat,high-fructose,high-cholesterol diet.After the successful establishment of the model,the golden hamsters were randomly divided into the model group,the lovastatin group,the lovastatin + β-glucan group,the low-dose and high-dose groups of highland barley Monascus purpureus Went.extract,and the golden hamsters fed with the control diet were used as the normal group.After 4weeks of continuous intragastric administration,the blood was collected in the medication group,the animals were sacrificed by cervical dislocation,and the liver tissue and adipose tissue were collected.The levels of triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)in serum were detected,and the liver index and fat index were calculated.The results of the liver pathological examination were analyzed to evaluate the effect of highland barley Monascus purpureus Went.on nonalcoholic fatty liver disease.The results showed that highland barley Monascus purpureus Went.extract could effectively inhibit the weight gain and liver index of golden hamsters induced by high-fat,high-fructose,high-cholesterol diet,and reduce abdominal fat and epididymal fat deposition.Lovastatin + β-glucan and highland barley Monascus purpureus Went.extract can effectively reduce the levels of TG,TC,and LDL-C in serum,and increase the level of HDL-C.Lovastatin + β-glucan and highland barley Monascus purpureus Went.extract can also improve the liver condition and reduce lipid accumulation in the liver.2.Effect of highland barley Monascus purpureus Went.on liver metabolites of nonalcoholic fatty liver disease based on metabolomicsThe metabolites in the liver of hamsters were detected by ultra-performance liquid chromatography-tandem mass spectrometry(UHPLC-Q Exactive),and the data were tested by principal component analysis and orthogonal least squares discriminant analysis to find the significantly different metabolites.The metabolites were annotated by the database to obtain information on differential metabolites,and the correlation between differential metabolites and pharmacodynamic indexes was analyzed.Through the enrichment analysis of the pathways involved in the differential metabolites,combined with the literature to find the anti-alcoholic fatty liver disease pathway.The results showed the effects of highland barley Monascus purpureus Went.on metabolites in the liver mainly involved sphingolipid metabolism,glycerophospholipid metabolism and choline metabolism pathways,and significantly reduced lipid accumulation in the liver by regulating lipid metabmetabolisms as ceramide,sphingolipid and glycerophospholipid.3.To explore the mechanism of highland barley Monascus purpureus Went.extract on nonalcoholic fatty liver disease based on fatty acid oxidation,fatty acid synthesis,and cholesterol metabolism pathwayWestern blot was used to detect the expression levels of fatty acid oxidationrelated proteins(PPARα,CPT1 A,ACOX1,ACSL1),fat synthesis-related proteins(SREBP-1,FAS,ACC,Ace CS1),and cholesterol metabolism-related proteins(HMGCR,LDLR,CYP7A1)in the liver of golden hamsters.The results showed that the highland barley Monascus purpureus Went.extract could increase the expressions of PPARα,ACOX1,CPT1 A,and ACSL1 in liver tissues of golden hamsters and liver mitochondria,and promote the oxidation of fatty acids in the liver.Highland barley Monascus purpureus Went.extract can reduce the expression of SREBP-1,FAS,and Ace CS1 in liver tissue,and reduce the synthesis of fatty acids in the liver.At the same time,lovastatin + β-glucan and highland barley Monascus purpureus Went.extract can reduce the HMGCR level in the liver,increase the expression of LDLR,and CYP7A1,reduce cholesterol synthesis in the body,and promote cholesterol metabolism.ConclusionHighland barley Monascus purpureus Went.extract has a therapeutic effect on nonalcoholic fatty liver disease induced by high fat,high fructose,and high cholesterol diet in golden hamsters.It can affect the changes of liver metabolites,regulate choline metabolism and lipid metabolism pathways.Its mechanism may be through increasing fatty acid oxidation,reducing fatty acid synthesis,and promoting cholesterol metabolism.β-glucan in highland barley Monascus purpureus Went.has an auxiliary effect on inhibiting hepatic steatosis. |
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