Study On The Mitigating Effects And Mechanisms Of Astragalus Mongholicus Polysaccharides Against NAFLD In Rats

Nonalcoholic fatty liver disease(NAFLD)is a metabolic disease related to obesity and type 2 diabetes,and has become a global public medical problem.However,due to its complex pathogenesis,people’s understanding of the disease is still limited.Currently,there is no approved drug for the treatment of NAFLD.The main clinical treatment methods are weiaght loss and targeted drug therapy,but its effectiveness and safety need to be further verified in clinical practice.Low toxicity and high efficiency plant active substances have become a new strategy to control NAFLD.Astragalus mongholicus polysaccharides(mAPS)is a polysaccharide component with antioxidant and anti-inflammatory activities extracted from Astragalus mongholicus Bunge.,which is used in traditional medicine to treat various metabolic related diseases.The purpose of this experiment is to explore the improvement effect and mechanism of mAPS on NAFLD.Methods:the content of mAPS was determined by phenol sulfuric acid method,and the monosaccharide composition was analyzed by HPLC.NAFLD rat model was induced by high fat diet(HFD).60 male SD rats were randomly divided into five groups:blank control group(CtrL),mAPS control group(mAPS,200 mg/kg),model group(HFD),mAPS treatment group(HFD+mAPS,200 mg/kg)and berberine treatment group(HFD+BERr,300 mg/kg).Except the Ctrl group and the mAPS control group,all the other groups were fed a high-fat diet for 4 weeks,and then treated With mAPS or berberine for 6 weeks.The visceral index,insulin resistance index,biochemical indexes of serum and liver,histological changes of liver and intestine,expression changes of lipid metabolism,antioxidant and inflammatory related factors,changes of gut microbiota and SCFA receptor were detected.Results:the content of Glucose in mAPS was 71.01%.The monosaceharide group consisted of Glucose(84.86%),Arabinose(4.49%),Galactose(3.92%)and Ribose(3.26%).After treatment with mAPS,the body weight,body fat and liver index of NAFLD rats were significantly reduced(p<0.05),the insulin resistance index(HOMA-IR)and the serum ALT and AST levels were significantly reduced(p<0.05).mAPS could significantly reduce TG,TC,LDL-C in liver tissue and serum of NAFLD rats,and increase serum HDL-C level(p<0.05).Liver oil red O staining showed that the accumulation of lipid droplets in the liver decreased significantly after the administration of mAPS.mAPS and berberine significantly increased phosphorylated adenylate activated protein kinase(p-AMPK)and peroxidase proliferator activated receptor in liver tissue-α(PPAR-α)The expression of SREBP-1 was decreased(p<0.05).mAPS and BER supplements reduced HFD induced expression of pro-inflammatory cytokines,such as TNF-α.mAPS down regulates TLR4 and phosphorylated NF-κB in intestine and liver and NLRP3,while up regulating the expression of ZO-1 and Occludin.It is worth noting that mAPS reshapes the intestinal microbiome by reducing the ratio of Firmicuies to Bacteroidetes and increase the abundance of Proteobacteria and Verrucomicrobia.The addition of mAPS had little effect on fecal short chain fatty acids(SCFA),but significantly reduced the expression of GPR41 and GPR43 in intestine and liver.Therefore,mAPS can improve liver inflammation and lipid accumulation in NAFLD by regulating gut microbiota and SCFA-GPR signaling pathway.The above results demonstrate that mAPS can improve NAFLD in rats by regulating lipid metabolism,oxidative damage,inflammation and gut microbiota composition.It provides experimental basis and theoretical support for mAPS in the treatment of NAFLD and its related diseases.