The Alleviating Effect And The Mechanism Of Holothuria Leucospilota Polysaccharide On Hyperlipidemia In Rats

As a global metabolic disease,hyperlipidemia seriously harms people's health.As a primary method for the treatment of hyperlipidemia,drug therapy is easy to produce resistance and side-effects.Therefore,it is particularly important to develop natural ingredients to make up for the deficiency of traditional drugs.Foodborne polysaccharides have a variety of functions such as anti-oxidation,anti-hyperlipidemia,anti-hyperglycemic and anti-tumor.Holothuria leucospilota is a marine resource riched in functional acid mucopolysaccharides.However,studies on the Holothuria leucospilota polysaccharide(HLP)and its digestive products are relatively scarce.This study has taken Holothuria leucospilota as the research object.The biological activities of HLP and its digestive products were preliminarily discussed,the characteristics of HLP digestion in vivo and in vitro were elucidated,the alleviating effect and the mechanism of HLP on hyperlipidemia in rats were revealed.The main contents and conclusion are as follows:(1)HLP was extracted and its physicochemical properties and antioxidant activity were measured.The digestive effects of saliva and gastrointestinal juice on HLP were studied by simulated digestion in vitro.The molecular weight(Mw)of HLP was approximately 52.80 k Da,and the monosaccharide composition was primarily fucose(35.72%)and rhamnose(39.08%).HLP showed good antioxidant activity at high concentrations(?2 mg/m L).Gastrointestinal digestion significantly reduced the Mw of HLP(from 52.80 k Da to 14.67 k Da and 12.01 k Da)and maintained better antioxidant activity.The decrease of Mw after gastric and intestine digestion was caused by the destruction of aggregates and the decomposition of glycosidic bonds,respectively.(2)In order to study the fermentation characteristics of HLP in vitro and in vivo,HLP was mixed with human fecal microorganisms and normal mice were intragastrically administered with different doses of HLP for 4 weeks.The results showed that the p H of feces decreased from 6.9 to 5.8,the content of reducing sugar decreased from 0.85 m M to 0.05 m M,and the content of SCFA increased significantly(p < 0.05),and there was free monosaccharides(rhamnose,fucose and xylose)production.In vivo digestion,the p H of feces decreased,the SCFA concentration and the antioxidant activity of the liver significantly increased in the HLP-treatment group(p < 0.05).This indicated that HLP could be utilized by gut microflora to produce SCFA,and improved the antioxidant activity of the liver.(3)Rats were given a high-fat diet and randomly divided into HFD,HLP-L and HLP-H,and rats fed with normal diet as ND.HLP was helpful to alleviate dyslipidemia(TC,TG and LDL-C),the abnormal levels of inflammatory factors(TNF-?,IL-6,IL-10 and IL-12),the impairment of oxidative stress(SOD,MDA and CAT)and liver function(AST and ALT)induced by high-fat diet.The pathological results showed that the infiltration of inflammatory cells in liver tissue decreased and the fat accumulation was relieved after HLP intake.It is suggested that HLP had a significant inhibitory effect on hyperlipidemia and a protective effect on the liver.(4)Metabonomics,high-throughput sequencing and western blotting were used to analyze the m RNA and protein expression related to liver lipid synthesis related,and serum metabolites were measured to further study the mechanism of HLP improving hyperlipidemia.The results showed that HLP was used by gut microflora to promote the production of SCFA and participate in the regulation of lipid metabolism.HLP could alleviate the accumulation of lipid in the liver by regulating NF-?B pathway and reducing the expression of ACC and CD36,so as to alleviate the hyperlipidemia in rats.In addition,there were six biomarkers were identified in this study,and HLP can alleviate liver injury by regulating nadolol and glycodeoxycholicacid contents in serum of hyperlipidemia rats.