Therapeutic Effect Of Total Flavonoids Of Broussonetia Papyrifera On Non-alcoholic Fatty Liver Disease In Mice

Non-alcoholic fatty liver disease（NAFLD）is a type of liver injury caused by other liver damaging factors,which is mainly characterized by excessive accumulation of fat in liver cells.Broussonetia papyrifera contains a large number of flavonoids,which have antioxidant,anti-inflammatory and anti-tumor properties.Therefore,we investigated the therapeutic effect of total flavonoids of Broussonetia papyrifera on NAFLD and its molecular mechanism.In this experiment,we obtained Total flavonoids of Broussonetia papyrifera by ethanol solution distillation,and measured the content of flavonoids.Two free fatty acids,oleic acid（OA）and palmitic acid（PA）,were used to induce Hep G2 cells to establish a model of lipid accumulation in vitro.Molecular biological technologies,including CCK-8,oil red O staining,western blot,were used to investigate the role of TFBP in oxidative stress and autophagy in cells.The results showed that low concentration of TFBP had no cytotoxicity to Hep G2 cells.There was plenty of lipid accumulation in Hep G2 cells stimulated by OA and PA,and TFBP pretreatment significantly reduced lipid accumulation in Hep G2 cells.The expression of Nrf2 in the nucleus and HO-1 in the cytoplasm was enhanced,indicating that TFBP promoted the translocation of Nrf2 into the nucleus.In this study,mice were fed with a 60%high fat diet for 6 weeks to establish a chronic model of NAFLD.For the next two weeks,mice were given treatment of TFBP by intragastric administration.The results showed that TFBP can reduce the blood total cholesterol（TC）,triglyceride（TG）and low-density lipoprotein cholesterol（LDL-C）levels,and increase the high-density lipoprotein cholesterol（HDL-C）levels.TFBP can effectively inhibit the production of reactive oxygen species（ROS）and decrease the content of myeloperoxidase（MPO）,and increase the activity of superoxide dismutase（SOD）to alleviate the injury from oxidative stress damage.Furthermore,TFBP reduced the accumulation of lipid in mice hepatocytes through promoting the expression of Nrf2 in nucleus.Tyloxapol blocks the removal of LDL-C from the blood and is often used to establish NAFLD in the body.In Nrf2^-/-mice stimulated by tyloxapol,the levels of lipid in blood of each group were higher than these in WT mice.In conclusion,the results of this study showed that TFBP has significant effects in alleviate oxidative stress,which is valuable in detected the mechanism and medicine in NAFLD.