HMGB1(high mobility group protein)has been established as a key inflammatory mediator associated with various chronic diseases,particularly in neuroinflammatory pathogenesis.In this work,the potential of chrysin(Chr)/...HMGB1(high mobility group protein)has been established as a key inflammatory mediator associated with various chronic diseases,particularly in neuroinflammatory pathogenesis.In this work,the potential of chrysin(Chr)/apigenin(Api)/luteolin(Lut)as natural functional food ingredients was evaluated on their interactions with HMGB1 through integrated multi-spectroscopic analysis.Surface plasmon resonance(SPR)results of Api and Lut showed the dissociation constants(KD)values of 2.991×10^(-5) M and 3.206×10^(-6) M,respectively,which indicated that the hydroxyl group on the B-ring of flavonoids may impact their binding affinity with HMGB1.Fluorescence spectroscopy and circular dichroism(CD)analyses revealed that the binding of three flavonoids to HMGB1 caused static quenching and significantly altered their spatial conformation,resulting in a reduction in theα-helix content from 60.71±1.30%to Chr(44.24±1.27%),Api(47.52±2.79%)and Lut(49.20±2.07%),respectively.The synchronous and three-dimensional fluorescence spectrum further revealed that these interactions led to the microenvironmental changes in the chromogenic amino acids in HMGB1.Molecular docking experiments indicated that hydrogen bonding was the primary force between the interaction of three flavonoids and HMGB1,and the key amino acids forming the hydrogen bonds included Lys94,Lys95,Asp98,and Arg104 residues.Furthermore,the three flavonoids could mitigate HMGB1-induced neuroinflammation on BV2 microglia cells in the bioassay.Due to the key role of HMGB1 in neuroinflammation and neurological disorders,Chr,Api,and Lut could be applied to improve the treatment of neurological diseases,and they also provided new insights for the development of new dietary supplements of flavonoids.展开更多
基金supported by the National Nature Science Foundation of China(Grant NO.21302052)the“Program for New Century Excellent Talents in University”for Prof.Jian Zhang(NECT-11-0739).
文摘HMGB1(high mobility group protein)has been established as a key inflammatory mediator associated with various chronic diseases,particularly in neuroinflammatory pathogenesis.In this work,the potential of chrysin(Chr)/apigenin(Api)/luteolin(Lut)as natural functional food ingredients was evaluated on their interactions with HMGB1 through integrated multi-spectroscopic analysis.Surface plasmon resonance(SPR)results of Api and Lut showed the dissociation constants(KD)values of 2.991×10^(-5) M and 3.206×10^(-6) M,respectively,which indicated that the hydroxyl group on the B-ring of flavonoids may impact their binding affinity with HMGB1.Fluorescence spectroscopy and circular dichroism(CD)analyses revealed that the binding of three flavonoids to HMGB1 caused static quenching and significantly altered their spatial conformation,resulting in a reduction in theα-helix content from 60.71±1.30%to Chr(44.24±1.27%),Api(47.52±2.79%)and Lut(49.20±2.07%),respectively.The synchronous and three-dimensional fluorescence spectrum further revealed that these interactions led to the microenvironmental changes in the chromogenic amino acids in HMGB1.Molecular docking experiments indicated that hydrogen bonding was the primary force between the interaction of three flavonoids and HMGB1,and the key amino acids forming the hydrogen bonds included Lys94,Lys95,Asp98,and Arg104 residues.Furthermore,the three flavonoids could mitigate HMGB1-induced neuroinflammation on BV2 microglia cells in the bioassay.Due to the key role of HMGB1 in neuroinflammation and neurological disorders,Chr,Api,and Lut could be applied to improve the treatment of neurological diseases,and they also provided new insights for the development of new dietary supplements of flavonoids.
