Molecular Simulation Study On Hypolipidemic Activity Of Konjac Glucomannan Compound

As the very plentiful substances,the increasingly high living standards and the changing dietary habits,the incidence of hyperlipidemia and other diseases rises year by year.This situation attracts people’s attention gradually.A lot of natural polysaccharides play important roles on regulation of lipid metabolism and decreasing the level of total cholesterol.Natural polysaccharides are nutritious and have health protection function,moreover,it has rather important regulation effects on immune and metabolism system and nervous transferring system of biological organism in organisms.Polysaccharide derives from a wealth of sources and owns excellent properties,such as renewable,biodegradable,biocompatible,etc.Some polysaccharides and its derivatives can interact or form molecular aggregates then present new physical and chemical properties and structures.The study of compounding polysaccharides is concerned by people always.Due to the special chemical structure of KGM,it possesses various good properties,such as water soluble,gel property,film forming ability,non-toxicity,degradability and so on.KGM has high application value on reducing blood lipid.Konjac polysaccharide has some characters,for example,strong water absorption,high viscosity and high expansion rate.Its special structure,β-1,4 glucosidic bond structure,can’t be degraded by digestive enzyme in the body.Konjac polysaccharide swells in body after imbibing,and forms gel as volume increasing,then it can fill you up for a long time,delaying the digestion of food.KGM can lower the serum cholesterol and blood lipids level effectively,and prevent and treat cardiovascular disease.KGM combines with cholic acid at digestive tract,accelerating the conversion of cholesterol into cholic acid,therefore,lowering serum cholesterol level.However,two mechanism studies of reducing blood lipid about KGM above are still on animal experiment,lacking the analysis of structure-activity of KGM’s reducing blood lipid from molecular level.For this reason,this paper starts with molecular conformation of KGM,and studies on reducing blood lipid of KGM by molecular dynamic and molecular docking.First,study the stability and viscosity of compound of KGM with carrageenan and Xanthan respectively by molecular dynamic.To find out KGM’s characteristic on stability and viscosity,and analyze its possible lipid-lowering effect.Then,using molecular docking to obtain the combination effect between KGM compound and sodium glycocholate,and elaborating the possible function pathways of KGM compound to sodium glycocholate and then studying its mechanism of reducing blood lipid.Finally,to analyze the verify relationship between the conformation of KGM compound and the effect of lipid-lowering effect by mice experiment and simulated results above.The main research results were as follows:(1)The hydrogen bond network was simulated under the conditions of vacuum and cycle by molecular dynamic,then,it could be found that KGM with carrageenan and xanthan not only formed hydrogen bonds in the molecules,but also formed a large number of hydrogen bonds between molecules.The hydrogen mainly produced on mannose residues O(6)of KGM and-OH of C(2)and C(3)of carrageenan and xanthan.The energy conformation,radial distribution function and mean square displacement of compound were studied by molecular dynamic,and it was found that the energy of compound in simulation could be quickly stabilized and the compound could form into stable gel.The compound had synergistic interaction on gel’s viscosity and hydrophily,therefore,it was inferred that the effect of reducing blood lipid enhanced after compounding.(2)The evaluation score was obtained by ZDOCK scoring function after blinding the molecules of compounds(KGM/carrageenan and KGM/xanthan)with sodium gllycocholate,and then simulated these two molecules which were blinded in the same environment.As a result of that,RMSD value of combination of the compound with cholic acid was achieved.The results showed that,the compound of KGM couldcombine with cholic acid,and the hydrogens could be bonded.The stability of conformation of compounds was becoming steady during the simulation,which showed that the polysaccharide of KGM compound could blind with cholic acid.The lipid-lowering effect of KGM/carrageenan was slightly better than KGM/xanthan.(3)The mixed feed of compound of KGM/carrageenan and KGM/xanthan could reduce serum TC and TG levels effectively.In the experiment,there was no significant reduction in weight of tree experimental mice groups,which were fed by there different feeds.These three kinds of feeds were put into KGM,KGM/carrageenan and KGM/xanthan respectively.The TC and TG levels of these three experimental mice groups were lower than high-fatty model group,at the same time,the HDL-C levels of these three medicated groups were increased.It turned out that these three polysaccharide groups could reduce blood lipid obviously.