Bioactivity Screening Of Polysaccharide SY01-23 Isolated From Morus Alba L.on Human Gut Microbiota And The Mechanism Underlying The Toxic Effect Of Its Main Residue Galacturonic Acid On Pancreatic β Cells

Polysaccharides isolated from Morus alba L.have rich biological activities in antidiabetes,antioxidant,anti-inflammatory,etc.Therefore,the research of mulberry leaf polysaccharides has attracted more and more attention.However,it is still vague whether the polysaccharides have impact on gut microbiota.Therefore,we explored the effects of polysaccharides SY01-21,SY01-22,and SY01-23 extracted from Morus alba L.on gut microbota.The results showed that SY01-21 could only promote the growth of Bacteroides cellulosilyticus(BC),while SY01-22 might only promote the growth of Bacteroides ovatus(BO),however SY01-23 could promote growth of both BO and BC.Based on the above results,SY01-23 was chosen for further exploration.Firstly,we demonstrated that SY01-23 had no significant activity against Lactobacillus rhamnosus GG(LGG),Lactobacillus reuteri(LR),and Bifidibacteria longum(BL).Secondly,the test results showed that BO and BC could degrade SY01-23 into monosaccharides and oligosaccharide fragments,and generate short-chain fatty acids including acetic acid and propionic acid which are beneficial to the human body.In addition,the study further showed that the growth rate of BO and Bacteroides thetaiotaomicron(BT)or BC and BT co-culture grew faster than that of BO or BC alone,suggesting that there might be a cross-feeding phenomenon among them.The above results suggested that the homogeneous polysaccharide SY01-23 might promote the growth of Bacteroides,and have a certain effect to improve intestinal health.Studies have reported that high concentrations of glucose can induce pancreatic β-cell apoptosis and reduce insulin secretion by stimulating islet β-cells to produce oxidative stress.Glucose is one of the 32 monosaccharides in nature.In order to investigate whether the other monosaccharides would damage islet β cells at high concentrations,we screened the effects from three common monosaccharides including Galacturonic acid(GalA),Arabinose(Ara),and Mannose(Man).The effect of survival rate showed that GalA was the most toxic to reduce cell survival rate.To this end,we then explored the toxic effect of high concentration GalA on islet β cells.The results showed that GalA could reduce the survival rate of cells by inducing apoptosis of INS-1E cells,stimulate INS-1E to produce excessive ROS,and activate ERK1 / 2,p38 MAPK and NF-κB-related signaling pathways to produce toxic effects.In addition,GalA might down-regulate the expression of insulin secretion(GSIS)-related genes stimulated by glucose,leading to reduced insulin secretion.In vivo experiments in mice showed that GalA could slow down the weight gain of mice and induce the increase of blood glucose in mice,further indicating that GalA had a toxic effect on islet β cells.The above results suggested that people should pay attention to the amount of GalA intake,so as not to cause damage to the human body.