The self-assembled nanoparticles(SAN)formed during the decoction process of traditional Chinese medicine(TCM)exhibit non-uniform particle sizes and a tendency for aggregation.Our group found that the p H-driven method...The self-assembled nanoparticles(SAN)formed during the decoction process of traditional Chinese medicine(TCM)exhibit non-uniform particle sizes and a tendency for aggregation.Our group found that the p H-driven method can improve the self-assembly phenomenon of Herpetospermum caudigerum Wall.,and the SAN exhibited uniform particle size and demonstrated good stability.In this paper,we analyzed the interactions between the main active compound,herpetrione(Her),and its main carrier,Herpetospermum caudigerum Wall.polysaccharide(HCWP),along with their self-assembly mechanisms under different p H values.The binding constants of Her and HCWP increase with rising p H,leading to the formation of Her-HCWP SAN with a smaller particle size,higher zeta potential,and improved thermal stability.While the contributions of hydrogen bonding and electrostatic attraction to the formation of Her-HCWP SAN increase with rising p H,the hydrophobic force consistently plays a dominant role.This study enhances our scientific understanding of the self-assembly phenomenon of TCM improved by p H driven method.展开更多
Intravenous nanosuspensions are attracted growing attention as a viable strategy for development of intravenous formulations of poorly water-soluble drugs.However,only few information about the biological fate of intr...Intravenous nanosuspensions are attracted growing attention as a viable strategy for development of intravenous formulations of poorly water-soluble drugs.However,only few information about the biological fate of intravenous nanosuspensions is currently known,especially amorphous nanosuspensions are not reported yet.In this study,the in vivo fate of herpetrione(HPE)amorphous nanosuspensions following intravenous administration was explored by using an aggregation-caused quenching(ACQ)probe and HPLC methods.The ACQ probe is physically embedded into HPE nanoparticles via anti-solvent method to form HPE hybrid nanosuspensions(HPE-HNSs)for bioimaging.HPE-HNSs emit strong and stable fluorescence,but fluorescence quenches immediately upon the dissolution of HPE-HNSs,confirming the selfdiscrimination of HPE-HNSs.Following intravenous administration of HPE-HNSs,integral HPE-HNSs and HPE show similar degradation and biodistribution,with rapid clearance from blood circulation and obvious accumulation in liver and lung.Due to the slower dissolution and enhanced recognition by reticuloendothelial system,450 nm HPE-HNSs accumulate more in liver,lung and spleen than that of 200 nm HPE-HNSs.These results demonstrate that integral HPE-HNSs determine the in vivo performance of HPEHNSs.This study provides insight into the in vivo fate of intravenous amorphous nanosuspensions.展开更多
Objective:Exploring the formation and aggregation of human islet amyloid polypeptide(hIAPP)(amylin)fibers is significant for promoting the prevention and treatment of type II diabetes mellitus(T2DM).Flavones in pomelo...Objective:Exploring the formation and aggregation of human islet amyloid polypeptide(hIAPP)(amylin)fibers is significant for promoting the prevention and treatment of type II diabetes mellitus(T2DM).Flavones in pomelo peel have visible biological activity in the anti-diabetes aspect.The present study aimed to investigate the effects of five flavones[naringin(NRG),narirutin(NRR),nobiletin(NOB),sinensetin(SIN),and neohesperidin(NHP)]in pomelo peel on peptide aggregation and explore its possible mechanisms.The cell viability of flavones against peptide aggregation was also evaluated.Methods:The thioflavin T(ThT)assay and transmission electron microscopy(TEM)were used for evaluating the inhibition and disaggregation of flavones on peptide aggregation.The interaction mechanism was analyzed by endogenous fluorescence,molecular dynamics(MD)simulations,ultraviolet spectroscopy(UV)and isothermal titration calorimetry(ITC)experiments.The 3-[4,5-dimethylthiazol-2-y l]-2,5-diphenyl tetrazolium bromide(MTT)and immune assays were performed to characterize the cell viability of flavones against peptide aggregation.Results:The five flavones showed a decrease in fluorescence intensity,fiber number and size under incubation with different molar ratios of hIAPP.The compounds can bind to the aromatic tyrosine(Tyr)residueTyr 37,resulting in the intrinsic fluorescence quenching of the peptides.Five flavones can form hydrogen bonds with hIAPP,which is likely to be based on their phenolic hydroxyl structure.They showed strong binding affinity with peptides.The reaction system of NRG and NRR observed an exothermic reaction,and the others were endothermic reactions.The absorption peaks of the compounds with hIAPP changed and showed hypochromic effects,indicating that there may beπ-πstacking interaction.Flavones noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide oligomers.Conclusion:A total of five flavones in pomelo peel have inhibitory and depolymerization effects on amyloid fibrils,and can significantly protect cells from the toxic effect of hIAPP and reduce the production of toxic oligomers.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81873092,82174074)。
文摘The self-assembled nanoparticles(SAN)formed during the decoction process of traditional Chinese medicine(TCM)exhibit non-uniform particle sizes and a tendency for aggregation.Our group found that the p H-driven method can improve the self-assembly phenomenon of Herpetospermum caudigerum Wall.,and the SAN exhibited uniform particle size and demonstrated good stability.In this paper,we analyzed the interactions between the main active compound,herpetrione(Her),and its main carrier,Herpetospermum caudigerum Wall.polysaccharide(HCWP),along with their self-assembly mechanisms under different p H values.The binding constants of Her and HCWP increase with rising p H,leading to the formation of Her-HCWP SAN with a smaller particle size,higher zeta potential,and improved thermal stability.While the contributions of hydrogen bonding and electrostatic attraction to the formation of Her-HCWP SAN increase with rising p H,the hydrophobic force consistently plays a dominant role.This study enhances our scientific understanding of the self-assembly phenomenon of TCM improved by p H driven method.
基金supported by the National Natural Science Foundation of China(Nos.81873092,81573697,82174074,81803741)。
文摘Intravenous nanosuspensions are attracted growing attention as a viable strategy for development of intravenous formulations of poorly water-soluble drugs.However,only few information about the biological fate of intravenous nanosuspensions is currently known,especially amorphous nanosuspensions are not reported yet.In this study,the in vivo fate of herpetrione(HPE)amorphous nanosuspensions following intravenous administration was explored by using an aggregation-caused quenching(ACQ)probe and HPLC methods.The ACQ probe is physically embedded into HPE nanoparticles via anti-solvent method to form HPE hybrid nanosuspensions(HPE-HNSs)for bioimaging.HPE-HNSs emit strong and stable fluorescence,but fluorescence quenches immediately upon the dissolution of HPE-HNSs,confirming the selfdiscrimination of HPE-HNSs.Following intravenous administration of HPE-HNSs,integral HPE-HNSs and HPE show similar degradation and biodistribution,with rapid clearance from blood circulation and obvious accumulation in liver and lung.Due to the slower dissolution and enhanced recognition by reticuloendothelial system,450 nm HPE-HNSs accumulate more in liver,lung and spleen than that of 200 nm HPE-HNSs.These results demonstrate that integral HPE-HNSs determine the in vivo performance of HPEHNSs.This study provides insight into the in vivo fate of intravenous amorphous nanosuspensions.
基金supported by the National Natural Science Foundation of China(No.82174074,81873092)。
文摘Objective:Exploring the formation and aggregation of human islet amyloid polypeptide(hIAPP)(amylin)fibers is significant for promoting the prevention and treatment of type II diabetes mellitus(T2DM).Flavones in pomelo peel have visible biological activity in the anti-diabetes aspect.The present study aimed to investigate the effects of five flavones[naringin(NRG),narirutin(NRR),nobiletin(NOB),sinensetin(SIN),and neohesperidin(NHP)]in pomelo peel on peptide aggregation and explore its possible mechanisms.The cell viability of flavones against peptide aggregation was also evaluated.Methods:The thioflavin T(ThT)assay and transmission electron microscopy(TEM)were used for evaluating the inhibition and disaggregation of flavones on peptide aggregation.The interaction mechanism was analyzed by endogenous fluorescence,molecular dynamics(MD)simulations,ultraviolet spectroscopy(UV)and isothermal titration calorimetry(ITC)experiments.The 3-[4,5-dimethylthiazol-2-y l]-2,5-diphenyl tetrazolium bromide(MTT)and immune assays were performed to characterize the cell viability of flavones against peptide aggregation.Results:The five flavones showed a decrease in fluorescence intensity,fiber number and size under incubation with different molar ratios of hIAPP.The compounds can bind to the aromatic tyrosine(Tyr)residueTyr 37,resulting in the intrinsic fluorescence quenching of the peptides.Five flavones can form hydrogen bonds with hIAPP,which is likely to be based on their phenolic hydroxyl structure.They showed strong binding affinity with peptides.The reaction system of NRG and NRR observed an exothermic reaction,and the others were endothermic reactions.The absorption peaks of the compounds with hIAPP changed and showed hypochromic effects,indicating that there may beπ-πstacking interaction.Flavones noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide oligomers.Conclusion:A total of five flavones in pomelo peel have inhibitory and depolymerization effects on amyloid fibrils,and can significantly protect cells from the toxic effect of hIAPP and reduce the production of toxic oligomers.
