The Effect Of Polygonatum Cyrtonema Polysaccharide On Nutritional Obesity Based On Metabolomics

Objective:Obesity is a nutritional metabolic syndrome characterized by abnormal energy metabolism and excessive accumulation of fat.Obesity has become a serious public health problem globally due to its increased morbidity in recent years.Polygonatum cyrtonema Hua is a perennial herb from family Liliaceae,and has been used in China for thousands years.The Chinese medicinal book “Mingyibielu” recorded that the rhizomes of genus Polygonatum could lose weight,prolong life,and resist hunger.Modern pharmacological studies have shown that P.cyrtonema can reduce blood glucose,blood lipids,and improve cardiovascular diseases.Polysaccharide is the main bioactive component of P.cyrtonema,whereas little is known regarding the anti-obesity effect and underlying mechanism of P.cyrtonema polysaccharide.In this study,the effect of P.cyrtonema Polysaccharide on nutritionally obese mice was studied,and its anti-obesity mechanism was further explored based on metabolomics.Methods:P.cyrtonema was extracted by hot water and precipitated with ethanol to obtain P.cyrtonema polysaccharide(PCP),which was used in animal experiments.The PCP powder was deproteinization,decolorization,dialysis,and freeze-drying for the composition and structure analysis,including the total carbohydrate contents detected by the phenol-sulfuric acid method,the molecular weight,monosaccharide composition and structural determined by HPGPC,GC,and FT-IR.The mice model of obesity was induced by high-fat-diet,the animal was randomly divided into the following groups: normal diet-fed(ND)group treated with a standard diet,HFD group treated with high-fat-diet,PCP250,PCP500 and PCP1000 respectively treated with 250 mg/kg,500 mg/kg and 1000 mg/kg PCP by daily oral gavage simultaneously with HFD feeding.The mice in the ND and HFD groups were given the same volume of distilled water.The body weights and food intake of mice were recorded weekly,and fasting blood glucose level was measured at the end of 12 weeks.The mice were euthanized after 12 weeks of treatment following a 12 h fast.Serum TC,TG,LDLC,and HDL-C levels were tested by Biochemical Analyzer,and serum leptin and insulin levels were assessed using ELISA.UPLC-Q-TOF/MS-based metabolomics was used to analyze endogenous metabolites in liver and serum.To identify and screened the endogenous differential metabolites in biological samples,the raw data were analyzed by Progenesis QI and matched with the HMDB online database.The structure metabolism was further identified by the MS/MS fragments information to identify the differential metabolites induced by high-fat diet and regulated by PCP were identified in liver and serum samples.The metabolic pathway was analyzed using Metaboanalyst 5.0 to further explore the effect of PCP on endogenous metabolites and metabolic pathways in HFD induced mice.Results:The molecular weight of the Polygonatum polysaccharide was 5.1 k Da,and it mainly consisted of galactose(37.30%),mannose(19.45%),rhamnose(18.78%),galacturonic acid(15.62%),and glucose(15.09%).PCP contained both α and β-glycoside.The results of pharmacodynamics showed that there was no significant difference in the daily energy intake of mice across the different groups.Compared with the ND group,body weight,weight gain,Lee’s and adipose index increased significantly in HFDinduced obese mice,also fasting blood glucose,TC,TG,LDL-C,leptin,and insulin increased significantly compared to that of the normal mice.Liver showed obvious steatosis and inflammatory infiltration,and adipocyte size significantly increased in model mice.After PCP intervention,the body weight,fasting blood glucose,and lipid deposition significantly decreased,the level of TC,TG,LDL-C,leptin,and insulin were restored,and the hepatic steatosis and adipocyte size were ameliorated.It suggested that PCP has an obvious effect on weight loss and lipid metabolism in HFD mice.Metabolomics analysis demonstrated that 39 differential metabolites induced by HFD were identified in liver.Among which,19 differential metabolites were regulated by PCP A total of 30 differential metabolites induced by HFD were detected in serum,and 11 of which were influenced by PCP.The metabolic pathways regulated by PCP in the liver and serum mainly include linolenic acid metabolism,arachidonic acid metabolism,glycerophospholipid metabolism.Conclusion:Polygonatum cyrtonema Polysaccharide effectively decreased body weight,blood lipid,and blood glucose,improved hepatic steatosis,reduce the volume of fat cells,and inhibit serum leptin level in HFD-induced obese mice.The effect of Polygonatum cyrtonema Polysaccharide on alleviating obesity might be regulated by arachidonic acid metabolism,glycerophospholipid metabolism,and linolenic acid metabolism.this research provides new insights into the anti-obesity mechanism of Polygonatum cyrtonema Polysaccharide.