Mulberry,an edible and medicinal fruit rich in polyphenolic compounds that improve gut health and metabolic diseases.Nevertheless,the effects of mulberry polyphenols(MP)against nonalcoholic fatty liver disease(NAFLD)r...Mulberry,an edible and medicinal fruit rich in polyphenolic compounds that improve gut health and metabolic diseases.Nevertheless,the effects of mulberry polyphenols(MP)against nonalcoholic fatty liver disease(NAFLD)remain unknown.This study aimed at utilizing 16s rRNA sequencing,network pharmacology combined transcriptomics technologies to explore the effects and molecular mechanisms of MP on NAFLD.Based on liquid chromatography-electrospray ionization high-resolution mass spectrometry(LC-ESI-HRMS)analysis,40 chemical ingredients were identified in MP.Male C57BL/6J mice were fed a Choline deficient,Lamino acid-defined,high-fat diet(CDAHFD)for six weeks to induce a NAFLD model and treated with MP at low(1 g/kg),medium(2 g/kg)and high(4 g/kg)doses.Pharmacodynamic analysis showed that MP significantly rectified serum biochemical indicators of liver function and lipid metabolism in NAFLD mice.Histopathological evaluation manifested MP was able to attenuate lipid accumulation,reduce hepatocellular necrosis and inflammatory infiltrates.Integrated network pharmacology and liver transcriptome sequencing revealed that MP regulated genes and signaling pathways involved in lipid metabolism and inflammatory response,such as PI3K-Akt,and related core proteins(PI3K,Akt,p-P3K,p-Akt,Nur77,and p21)were further validated by western blotting.Additionally,16s rRNA gene sequencing demonstrated that MP treatment effectively remodeled intestinal microbiota imbalances by reducing possibly harmful bacteria(Romboutsia and Roseburia)and promote potential beneficial bacteria(Muribaculaceae and Bacteroidota).Collectively,this study depicted the comprehensive mechanisms though which MP can alleviate NAFLD,which highlights the nutritional value of MP as a dietary adjuvant for the treatment of NAFLD.展开更多
基金financially supported by the National Natural Science Foundation of China(No.82004069)the Fundamental Research Funds for the Central Universities of Southwest Minzu University(3300224036)the Innovation and Entrepreneurship Training Program of Southwest Minzu University(202310656009).
文摘Mulberry,an edible and medicinal fruit rich in polyphenolic compounds that improve gut health and metabolic diseases.Nevertheless,the effects of mulberry polyphenols(MP)against nonalcoholic fatty liver disease(NAFLD)remain unknown.This study aimed at utilizing 16s rRNA sequencing,network pharmacology combined transcriptomics technologies to explore the effects and molecular mechanisms of MP on NAFLD.Based on liquid chromatography-electrospray ionization high-resolution mass spectrometry(LC-ESI-HRMS)analysis,40 chemical ingredients were identified in MP.Male C57BL/6J mice were fed a Choline deficient,Lamino acid-defined,high-fat diet(CDAHFD)for six weeks to induce a NAFLD model and treated with MP at low(1 g/kg),medium(2 g/kg)and high(4 g/kg)doses.Pharmacodynamic analysis showed that MP significantly rectified serum biochemical indicators of liver function and lipid metabolism in NAFLD mice.Histopathological evaluation manifested MP was able to attenuate lipid accumulation,reduce hepatocellular necrosis and inflammatory infiltrates.Integrated network pharmacology and liver transcriptome sequencing revealed that MP regulated genes and signaling pathways involved in lipid metabolism and inflammatory response,such as PI3K-Akt,and related core proteins(PI3K,Akt,p-P3K,p-Akt,Nur77,and p21)were further validated by western blotting.Additionally,16s rRNA gene sequencing demonstrated that MP treatment effectively remodeled intestinal microbiota imbalances by reducing possibly harmful bacteria(Romboutsia and Roseburia)and promote potential beneficial bacteria(Muribaculaceae and Bacteroidota).Collectively,this study depicted the comprehensive mechanisms though which MP can alleviate NAFLD,which highlights the nutritional value of MP as a dietary adjuvant for the treatment of NAFLD.
