| Long-term hyperlipidemia will cause atherosclerosis and other cardiovascular diseases,which seriously harm people’s health.At present,the existing therapeutic drugs are mainly statins,and most of these drugs have toxic and side effects.Therefore,it is urgent to explore the natural product resources with little toxic and side effects and significant pharmacological effects.Pleurotus abieticola polysaccharides(PAPS 1),a neutral polysaccharide extracted from the fruiting body of abies polysaccharides,has been demonstrated to have immunomodulatory activities.However,the regulatory role of PAPS1 in hyperlipidemia remains unclear.By establishing dietinduced obsisity(DIO)animal model induced by High-fat Diet(HFD),this study systematically analyzed the regulation effect of PAPS1 on lipid and lipid metabolism in DIO mice,and preliminarily identified its mechanism,the specific contents are as follows:First,selected 48 3-week-old C57BL/6J mice,12 were fed a normal diet and recorded as blank control group(normol control diet,NCD),and 36 were fed a high-fat diet(60%fat)for 8 weeks to establish the DIO mouse model.They were randomly divided into 3 groups with 12 animals in each group.The high fructose corn syrup(HFD)group was intragastrically gavage 5 mL/kg sterile water,the high fructose corn syrup+SV group was intragastrically gavage 3 mg/kg Simvastatin(SV),and the high fructose corn syrup+PAPS1 group was intragastrically gavage 100 mg/kg PAPS1.PAPS1 was found to significantly inhibit weight gain and restore blood sugar levels in HFD mice 4 weeks after administration.Secondly,histopathological analysis showed that PAPS1 could improve lipid accumulation,inflammatory cell infiltration and adipose cell enlargement in the liver of HFD mice,and no significant lesions in other organs.Organ index analysis showed that PAPS1 could reduce liver and adipose tissue index of HFD mice.PAPS1 can improve the symptoms of hyperlipidemia,down-regulate the levels of TC,TG and LDL-C,and up-regulate the levels of HDL-C.Further untargeted metabolomics analysis of cecal contents showed that PAPS1 could downregulated metabolite 4,4-Thiodiphenol and up-regulated Pentadecanoic acid level,and the two showed negative correlation.In addition,PAP S1 can significantly inhibit the expression of cytokines TNF-α,IL-1β,IL-6,IL-17A,IL-22,IL-23 and oxidative stress factor ROS in liver,and promote the expression of anti-inflammatory factor IL-10,indicating that PAPS1 can inhibit the inflammatory response caused by obesity.Finally,by liver proteomics combined with western blot analysis,PAPS1 could also inhibit lipid accumulation by up-regulating the expression of Cregl,Gls2 and Gsta4 proteins and downregulating the expression of 4-HNE.western blot analysis confirmed that PAPS1 may regulate lipid metabolism through NF-κB/STAT3 signaling pathway.In conclusion,our study suggests that PAPS1 may regulate inflammatory factors through NF-κB/STAT signaling pathway,relieve symptoms of hyperlipidemia and regulate lipid metabolism.The results of this study will provide research basis for the development of drugs to reduce blood lipids. |