Vitexin Supplement Ameliorates The Aggravated Hepatic Steatosis And Inflammation By Chronic Stress In High-fat Diet-fed Mice

Nonalcoholic fatty liver disease(NAFLD)is one of the most common form of liver disease worldwide.The prevalence of NAFLD is regarded as a consequence of a sedentary food-abundant lifestyle which often coincides with long-lasting and chronic stress.Food-abundant lifestyle can induce nonalcoholic fatty liver disease(NAFLD),while chronic stress(CS)can aggravate the pathogenesis of NAFLD.The international guidelines reported that interventions such as diet and exercise are the only therapies suggested in NAFLD patients,no pharmaceutical agents are currently available for the treatment of NAFLD.Therefore,many complementary therapies and in particular herbal medicine aimed at key factors that regulate lipid metabolism and inflammation in the liver are been studied to treat NAFLD.Previous studies and academic studies have shown that vitexin has good effects on lipid metabolism and anti-inflammatory activity.Based on these,the subject simulates the high pressure and nutrient-enriched environment in modern society,and validates the effects of the two factors on the liver.This subject put forward "Vitexin supplement ameliorates the aggravated hepatic steatosis and inflammation by chronic stress in high-fat diet-fed mice" as the scientific hypothesis.We study that vitexin can protect against chronic stress combined with high fat diet induced liver steatosis and inflammation in mice.ObjectiveTo preliminary evaluate whether vitexin has a efficacy in protecting against chronic stress combined with high fat diet induced liver injury in mice,and assess vitexin impact on SREBP-1c/FAS/ACC pathway and TLR4/NF-?B pathway in chronic stress mice with high fat diet,including SREBP-1c,FAS,ACC,TLR4 and NF-?B mRNA and protein,as well as effects on activation and infiltration of macrophages and neutrophils.Methods1.The effect of vitexin on liver in chronic stress combined with high fat diet induced miceMale C57BL/6 mice were randomly divided into five groups.The treatment were as follows: Control group,mice were fed a basal diet;chronic stress group(CS group),mice were fed a basal diet and subjected to chronic strain stress;High fat diet group(HFD group),mice were fed high fat diet;Chronic stress with high fat diet group(CSHFD group),mice were fed high fat diet and subjected to chronic stress;Vitexin group(VX group),mice were fed a high fat diet supplemented with vitexin(40mg/kg/day)and subjected to chronic strain stress for 5 weeks.Test indicators: body weight,liver weight,spleen weight,thymus weight,liver index,spleen index,thymus index;serum AST,ALT,TC,TG;liver TC,TG,TNF-?,IL-6 and histological analysis of liver.2.The mechanism of vitexin on hepatic lipid deposition and inflammatory infiltration in chronic stress combined with high fat diet induced miceThe expression of the lipid synthesis pathways SREBP-1c/FAS/ACC and TLR4/NF-?B related genes and proteins in the liver tissue,as well as the activation and infiltration of macrophages and neutrophils were detected.Results1.Effect of vitexin on hepatic lipid deposition in chronic stress combined with high fat diet induced miceCompared with the control group,the serum and liver TC levels in the HFD group and the CSHFD group were significantly increased;the serum TG levels were only significantly increased in the CSHFD group,while the liver TG levels were significantly increased in the CS group,HFD group and CSHFD group(p<0.01).Administration of vitexin lasting 5weeks can significantly reduce serum and liver TC,TG levels in chronic stress combined with high fat diet induced mice(p<0.01).Compared with the control group,the serum AST levels in the HFD group and the CSHFD group were significantly increased(p<0.01),whereas in the serum ALT level,only the CSHFD group was significantly increased(p<0.01),administration of vitexin can reduce serum AST and ALT levels(p<0.01).It is suggested that the two factors of high fat and chronic stress can lead to liver lipid deposition and liver injury in mice.Vitexin can improve the liver damage.2.vitexin on lipid synthesis SREBP-1c / FAS / ACC pathwayIn chronic stress combined with high fat diet induced mice,the mRNA and protein expression of SREBP-1c,FAS,and ACC were significantly reduced after the treatment with vitexin(p <0.05 or p <0.01).3.Effect of vitexin on liver inflammatory infiltration in chronic stress combined with high fat diet induced miceCompared with the Ctr group,the levels of TNF-? and IL-6 in the liver tissue of the CSHFD group were significantly increased.The administration of vitexin can significantly reduce the level of TNF-? in the liver(p<0.01).4.The mechanism of Vitexin on improving liver inflammatory infiltration in chronic stress combined with high fat diet induced mice5.In chronic stress combined with high fat diet induced mice,the mRNA and protein expressions of TLR4 and NF-?B were significantly increased after vitexin treatment(P<0.05 or P <0.01).The expression of macrophages and neutrophils in livers of chronic stress combined with high fat diet induced mice was significantly higher than that in Ctr group,the CS group and the CSHFD group.After administration of vitexin,the expression of macrophages and neutrophils decreased.ConclusionVitexin can improve lipid deposition and inflammatory infiltration in the liver of chronic stress mice fed with high fat diet,and its effect may be through inhibition of lipid synthesis pathway SREBP-1c / FAS / ACC,inflammatory pathway TLR4 / NF-?B and reducing the infiltration of macrophages and neutrophils.