基于肠道菌群和代谢组学的五味子高压饮片与传统饮片对非酒精性脂肪肝小鼠的药效对比研究OA

This paper aims to evaluate the feasibility of clinical application of high-pressure Schisandrae Chinensis Fructus decoction pieces(HPSCH)compared with that of traditional Schisandrae Chinensis Fructus decoction pieces(SCH),based on the efficacy of mice with nonalcoholic fatty liver disease(NAFLD)induced by a high-fat diet.The optimal preparation process of HPSCH was investigated by using schisandrin content and total extractive yield as indices.After one week of adaptive feeding,C57BL/6 mice were assigned to a normal control group,while the remaining mice were fed an HFD for eight weeks to establish the NAFLD mouse model.After being successfully modeled,the mice were divided into a blank control group,blank administration group,simple model group,fenofibrate group,SCH group,and HPSCH group.All groups were administered by intragastric administration for four weeks.Body weight changes of mice were recorded,and liver indices were calculated.The levels of blood lipid and liver function index in the serum of mice were measured.Hepatic histopathological changes were observed by using hematoxylin-eosin(HE)staining and oil red O staining.Mice's feces were collected,and the 16S rDNA high-throughput sequencing method was employed to analyze changes in the gut microbiota of mice.Untargeted lipidomic analysis of the liver was conducted by using liquid chromatography-mass spectrometry(LC-MS),and principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were adopted to screen and identify differential metabolites.Kyoto Encyclopedia of Genes and Genomes(KEGG)database was used to perform relevant pathway analysis.Integrated analyses of gut microbiota and differential metabolites were performed to compare the similarities and differences in efficacy of HPSCH and SCH.The results show that both the HPSCH group and SCH group exert similar effects on biochemical indices in serum and hepatic pathological changes,lipid metabolism can be regulated,and liver injury in NAFLD mice can be improved.The two groups show similar changes in microbial abundance,trending toward the blank control group and maintaining intestinal homeostasis.Compared with those of the simple model group,the differential metabolites and metabolic pathways of both the HPSCH group and SCH group show similarity,and the differential metabolites are mainly triglycerides,diglycerides,phosphatidylcholines,phosphatidylglycerols,and so on.Metabolic pathways include glycerophospholipid metabolism,choline metabolism,retrograde endocannabinoid signaling,thermogenic lipolysis,and so on.This indicates that HPSCH and SCH share common advantages in improving hepatic function in mice and achieve comparable effects.HPSCH can improve blood lipid and liver function indices in NAFLD mice,attaining the therapeutic effect through the regulation of gut microbiota and lipid metabolism.Notably,HPSCH achieved the same efficacy as SCH at half the conventional dose,demonstrating its feasibility for clinical application.Moreover,the application of HPSCH may contribute to the conservation of medicinal resources.