Search

Objective: The Non-targeted metabolomics technology was used to analyze the metabolites in the serum and liver of mice with chronic alcoholic liver injury (ALD), to identify and screen out the differential metabolites related to alcoholic liver injury and construct its metabolic pathway, and to explore the protective mechanism of puerarin against alcoholic liver injury in mice. Methods: The mouse model of chronic alcoholic liver injury was established by intragastric administration of 52 liquor for 8 weeks. Meanwhile, the protective effects of puerarin on ALD mice were evaluated using biochemical indexes of liver function and pathological tissue sections. Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) metabonomics technique was used to analyze the metabolites of mouse liver and serum. Multivariate statistics were used to process the data, and the variable importance projection (VIP) of the first principal component was >1 and the t-test P<0.05 was used to screen out the differential metabolites. Metabolic pathways of differential metabolites using KEGG database. Results: Puerarin could significantly improve ALT and AST levels in alcohol-induced liver injury mice (P<0.05 or P<0.01). Furthermore, the pathological section results indicated that puerarin could improve liver inflammatory cell infiltration in ALD mice. Through multivariate statistics, 11 metabolites were found in serum metabolites between the model group and the blank group. Under puerarin intervention, the levels of 11 metabolites tended to blank group, mainly related to amino acid synthesis and metabolism, glutathione metabolism, porphyrin metabolism and chlorophyll metabolism. There were 32 different metabolites between the model group and blank group in liver metabonomics, and the levels of 31 different metabolites tended to blank group under puerarin intervention, which mainly involved the amino acid synthesis and metabolism, biosynthesis of primary bile acids, purine metabolism, phosphatidylinositol signalling system, steroid metabolism and other metabolic pathways. Conclusion: Puerarin has a protective effect on alcoholic liver injury in mice, and its mechanism may be through regulating the disorder of serum and liver metabolites, which provides a valuable reference for anti-alcoholism health food in the future. [ABSTRACT FROM AUTHOR]

Background: In modern diets, alcohol consumption has led to an increase in the number of cases of alcohol-related liver disease (ALD). Dihydromyricetin (DMY) is commonly used as a hepatoprotective agent owing to its remarkable efficacy in treating chronic alcoholic liver injury; however, its mechanism of action is unclear. The object of the study is to investigate the effect and mechanism of DMY in alleviating chronic ALD. Methods: A mouse model of chronic ALD was established. Mice were treated with DMY for 56 days, and their biochemical parameters including liver function, blood lipids, and oxidative stress-related indices were measured. Farnesoid X receptor (FXR) expression, NOD-like receptor protein 3 (NLRP3) pathway-related protein expression, and inflammation-related gene expression were determined to elucidate the mechanism of DMY in mice with ALD. Lastly, serum and liver metabolomics-based UHPLC-Orbitrap Exploris MS analyses were used to determine the influence of the metabolism of DMY on mice with ALD. Results: Pharmacodynamic studies showed that DMY could decrease aspartate transaminase, alanine transaminase, triglyceride, and low-density lipoprotein cholesterol levels, improve superoxide dismutase activity, and reduce inflammation in mice with ALD. DMY treatment protects the liver by increasing FXR protein expression and by decreasing NLRP3 pathway-related protein expression and inflammatory gene expression. Metabolomics analysis indicated that ethanol treatment mainly altered metabolism in mice. DMY could regulate 10 metabolites in serum, namely, N-α-acetyllysine, 1-pyrrolinecytosine, glutamyllysine, 5-methylcytosine, N-methylvaline, pyridoxamine, demethoxycurcumin, L-arginine, triacetin, and 15-methylpalmitate. It could also regulate 31 metabolites in the liver, including L-methionine and L-leucine. DMY treatment altered the following important pathways: valine, leucine, and isoleucine biosynthesis; cysteine and methionine metabolism; and valine, leucine, and isoleucine degradation. Correlation analyses using heatmaps revealed that the metabolic parameters are closely related to the pharmacodynamic index. Conclusion: These findings indicated that DMY alleviated ALD by regulating the FXR-NLRP3 signaling pathway and could treat serum and liver metabolic disorders. [ABSTRACT FROM AUTHOR]

At present,the global form of hypertension is severe,and liver-yang-hyperactivity hypertension（GYSK hypertension）is the most common type of hypertension.Folium Polygoni Cuspidati（HZY）are mainly used in Yunnan, China,to treat dizziness, headache,and hypertension caused by GYSK,and the content of the active ingredients of HZY and its efficacy varies in different periods.However,the mechanism of action and the effect of harvesting period are not clear. The purpose of this research was to investigate the effect of HZY in April and September on GYSK hypertension. The model of GYSK hypertension was established with aconite decoction and L-NAME,and the blood pressure,the symptoms of GYSK,the cardiac index and the pathological changes of aorta were observed,to study the effect of HZY in April and September on GYSK hypertension.The chemical composition of HZY was analysed by UPLC-QTOF-MS and its mechanism for the treatment of GYSK hypertension was predicted by network pharmacological studies and experimentally validated using serum metabolomics and Western blot techniques. April HZY and September HZY can significantly improve the GYSK symptoms of rats, inhibit the RAAS system, improve oxidative stress and regulate blood lipids so as to play a blood pressure lowering efficacy and have a protective effect on the vascular endothelial cells.UPLC-QTOF-MS yielded 29 components of HZY,and network pharmacology predicted that its mechanism may be related to Lipid and atherosclerosis,PI3K/Akt signaling pathway, MAPK signaling pathway and TNF signaling pathway,etc.Western Blot validation showed that HZY activated PI3K,p-Akt protein expression and inhibited p-erk,p-p38 and TNF-α protein expression.Serum metabolomics suggested that April HZY exerts its efficacy mainly by regulating amino acid metabolism and September HZY mainly by regulating lipid metabolism. In GYSK hypertensive rats treated for three weeks, both April HZY and September HZY could have antihypertensive effects,but the mechanisms of action were different and similar, both could regulate metabolite disorders of sugars, lipids,amino acids and peptides,and regulate blood pressure through the PI3K/Akt-eNOS and MAPK signalling pathways, with the difference that April HZY had stronger regulatory effects on the metabolism of amino acids.metabolism. [Display omitted] [ABSTRACT FROM AUTHOR]