| With the improvement in living conditions and the increasing risks of chronic diseases towards human health,diabetes mellitus and its correlated complications significantly affected human health around the world.L cell,which located in the colon,could be stimulated by food bioactive factors for secreting glucagon-likepeptide-1(GLP-1)that could modulate blood glucose level via the gut-brain axis.Addressing the distribution and extraordinary functions of L cell,this study aimed to prepare colon-targeting starch-lecithin-based delivery system that could overcoming the multiple physical barriers in the gastrointestinal tract through(i)modulating the interactions between starch,lecithin,and β-lactoglobulin,and(ii)tailoring lecithin distribution in the delivery system.The delivery system prepared herein was then used for stimulating GLP-1 secretion by L cell for modulating human blood glucose level.This study will provide a promising pathway to modulate human blood glucose level via stimulating enteroendocrine to secrete GLP-1 and guide the usage of gut-brain axis for improving human health.This work firstly collected long starch chains from pullulanase-treated starch using the centrifugation method,then tailored starch digestibility,charged property and wettability via controlling the interaction of starch with lecithin and then the modification by octenyl succinic anhydride(OSA),for meeting the requirement of low digestibility and assemblability of the materials that were used for synthesizing colon-targeting delivery systems.Results showed that short starch chains dissolved in water could be removed via cooling and centrifuging the pullulanase-treated starch solution.Starch long chains could be collected via modulating the temperature and the centrifugal force during the centrifugation.Starch long chains could be collected if the centrifugal force decreased during the centrifugation of the hot starch solution.Finally,the average starch chain length increased from 22.72 to 30.81.While the reverse solvent method using water and dimethyl sulfoxide(DMSO)was employed for synthesizing starch-lecithin complexes,the system with a water/DMSO ratio of 1.5/1 or 2.5/1promoted the formation of starch-lecithin inclusion complexes with a high proportion of V-type crystals but low content of B-type crystal.Starch-lecithin complexes prepared with long starch chains containing more starch-lecithin inclusion complexes,V-type crystals,and lecithin content(the highest lecithin content was 34.16 mg/g starch).The esterification of starch-lecithin with OSA significantly increased starch hydrophobicity with degree of substitution(DS)of 0.0187-0.0196.The OSA-modified starch-lecithin complexes showed B+V hybrid crystalline structures with unchanged V-type and B-type crystals comparing with the complexes without OSA modification.The resistant starch of the OSA-modified complexes was in the range of 41.21%-48.02%,which showed a promising potential to develop colon-targeting carriers.OSA-modified starch-lecithin complex-based delivery system was then prepared while the OSA-modified complex interaction with β-lactoglobulin in a controllable behavior.OSA-modified complex interacted with β-lactoglobulin mostly through hydrophobic interaction,and this reaction was more active at p H 4 and temperature of 35 ℃.OSA-modified complexes with similar DS of OSA but different starch chain distribution showed different interaction with β-lactoglobulin.The complexes with a more starch chains whose molar mass was smaller 10000 g/mol showed a stronger interaction withβ-lactoglobulin,which contributed to a higher β-lactoglobulin encapsulation efficiency,a higher structural compactness,a higher stability at different conditions(dilution,different salt and p H solution,and storage),and better colon-targeting β-lactoglobulin release properties of the delivery system had.When the delivery system transited from the upper gastrointestinal tract to the colon,the binding affinity of the OSA-modified complexes with β-lactoglobulin reduced,and starch of the delivery system was slowly digested along with the structural compactness of the delivery system gradually decreased.Such changes of the delivery systems thereby contributed to β-lactoglobulin colon-targeting release in the colon.Addressing the molecular mechanism of the formation of the delivery systems,the delivery systems were structured with different lecithin distribution(i.e.,controlling lecithin distribution in the hydrophobic cavity of starch molecules)for modulating structures andβ-lactoglobulin colon-targeting release properties of the systems.Lecithin,which acted as molecular chaperone,could interact with octenyl group of the OSA-modified complexes and then synergistically contributed to the formation of a hydrophobic cavity,which enabled OSA-modified complexes interaction with β-lactoglobulin.Lecithin-mediated assembled delivery systems thereby showed a higher encapsulation efficiency of β-lactoglobulin(increased from 61.98% to 70.69%),a higher structural compactness,a higher stability towards different processing conditions(dilution,different salt and p H solution)and storage,and better colon-targeting of β-lactoglobulin.Lecithin interacted with starch hydrophobic cavity and formed starch-lecithin inclusion complexes,which reduced starch digestibility.On the other hand,lecithin chaperoned with octenyl group of the OSA-modified complexes and hydrophobic cavity of β-lactoglobulin,which retarded the octenyl group of the OSA-modified complexes escape from the hydrophobic cavity of β-lactoglobulin.Such an interaction of lecithin with OSA-modified complexes and β-lactoglobulin thereby improved stability,structural compactness,and in turn the colon-targeting delivery of β-lactoglobulin of the delivery system.The delivery systems showed a low binding affinity and permeability towards mucus.Such behaviors enabled β-lactoglobulin targeting release in the colon and then the interaction with L cell.The delivery systems,which were digested in the upper gastrointestinal tract,significantly increased GLP-1 secretion through stimulating L cell as a function of stimulation time and the concentration of the digested delivery systems.Additionally,the delivery systems released β-lactoglobulin and lecithin and produced short-chain fatty acids,and reducing sugar while the systems were fermented by colonic microbia,which also significantly stimulated GLP-1 secretion.The delivery systems containing different lecithin distribution showed a stronger ability to stimulate GLP-1 secretion.It can be concluded that structures and the ability to stimulate GLP-1 secretion could be rationally modulated through tailoring lecithin distribution in the delivery system.This study established a solid method to collect long starch chains,and provided a clear understanding on the effects of lecithin distribution on structures of starch-lecithin complexes and structural features and colon-targeting delivery properties of the delivery systems.The delivery systems were successfully structured via modulating lecithin distribution,and in turn effectively promoted GLP-1 secretion through stimulating L cell.These findings of this study will guide the development of health-promoting foods and provided a promising pathway to control human blood glucose level via stimulating secretion of gut hormone by the food-derived bioactive factors that colon-targeting released in the colon. |
