基于肠道菌群和血清代谢组学探讨蝶豆花减轻非酒精性脂肪肝小鼠肝脏损伤的机制OA

Objective:To investigate the therapeutic effect and mechanism of Clitoria ternatea flower(CF)on non-alcoholic fatty liver disease(NAFLD)in mice induced by a high-fat diet(HFD).Methods:Twenty-four healthy ICR mice were randomly divided into four groups:normal control group(NC group),NAFLD model group(NAFLD group),high-dose CF group(CFH group,200 mg/kg),and low-dose CF group(CFL group,100 mg/kg),with 6 mice in each group.The NC group was fed a normal diet,while the NAFLD,CFH,and CFL groups were fed a 60％high-fat diet to induce NAFLD.Additionally,the CFH and CFL groups received corresponding doses of CF by gavage,and the NC and NAFLD groups received an equal volume of normal saline(0.6 mL)by gavage daily for 12 weeks.Serum levels of hepatic enzymes,blood lipids,and oxidative stress factors were detected,combined with untargeted metabolomics analysis.Fecal microbiota composition was analyzed via 16S rRNA gene sequencing,and the contents of three major short-chain fatty acids(acetate,propionate,and butyrate)were determined.Meanwhile,hepatic inflammation-related indicators were examined by quantitative real-time polymerase chain reaction(qRT-PCR).Results:Compared with the NAFLD group,the CFL and CFH groups showed significant reductions in serum levels of alanine aminotransferase(ALT),triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)(all P＜0.05).In the liver,the mRNA expressions of pro-inflammatory cytokines IL-1β and TNF-α were decreased,while those of anti-inflammatory cytokines IL-4 and IL-10 were increased(all P＜0.01).Additionally,serum superoxide dismutase(SOD)activity was markedly enhanced,whereas malondialdehyde(MDA)content was significantly decreased(all P＜0.01).16S rRNA sequencing results indicated that compared with the NAFLD group,the CF groups had increased abundances of multiple beneficial gut bacteria including Prevotella and Lactobacillus,along with elevated concentrations of acetate,propionate,and butyrate in feces.Serum untargeted metabolomics analysis revealed that compared with the NAFLD group,the CF groups had higher levels of various anti-inflammatory and anti-oxidative stress metabolites,which were mainly involved in glycerophospholipid metabolism,pyrimidine metabolism,and other pathways.Conclusion:CF can alleviate liver damage in NAFLD mice by improving lipid levels and hepatic inflammation,regulating gut microbiota balance and serum metabolic pathways,showing potential therapeutic effects for NAFLD.