Unreported tautomeric/enantiomeric meroterpenoids,(±)-hyperjaponols I—K(1-3),were discovered from Hypericum japonicum.Comprehensive chemical investigations established the absolute characteristics of these stere...Unreported tautomeric/enantiomeric meroterpenoids,(±)-hyperjaponols I—K(1-3),were discovered from Hypericum japonicum.Comprehensive chemical investigations established the absolute characteristics of these stereoisomers.The TS calculation demon-strated that 1a and 2a easily occur enol-keto tautomerism with steady configurations individually.Amongst isolates,1b showed the strongest neuroprotective activity with the concentration at 25μmol/L on H_(2)O_(2) insult SH-SY5Y cells.In vitro molecular biological ex-periments manifested that 1b activated the Keap1-Nrf2-ARE pathway,leading to the promotion of Nrf2 nuclear translocation,down-regulation of the expression level of Keap1,and upregulation of the levels of Nrf2,NQO-1,and HO-1.The results of in silico simulation showed that 1b possessed good binding features with Keap1(5FNQ)via forming multiple typical hydrogen and hydrophobic bonds as well as less fluctuation of RMSD and RMSF during a natural physiological condition.展开更多
基金This work was financially supported by the National Natural Science Foundation of China(No.31700298)the Innovation and Entrepreneurship Training Program for Undergraduates(Hubei Province,China)(No.S202010512054).
文摘Unreported tautomeric/enantiomeric meroterpenoids,(±)-hyperjaponols I—K(1-3),were discovered from Hypericum japonicum.Comprehensive chemical investigations established the absolute characteristics of these stereoisomers.The TS calculation demon-strated that 1a and 2a easily occur enol-keto tautomerism with steady configurations individually.Amongst isolates,1b showed the strongest neuroprotective activity with the concentration at 25μmol/L on H_(2)O_(2) insult SH-SY5Y cells.In vitro molecular biological ex-periments manifested that 1b activated the Keap1-Nrf2-ARE pathway,leading to the promotion of Nrf2 nuclear translocation,down-regulation of the expression level of Keap1,and upregulation of the levels of Nrf2,NQO-1,and HO-1.The results of in silico simulation showed that 1b possessed good binding features with Keap1(5FNQ)via forming multiple typical hydrogen and hydrophobic bonds as well as less fluctuation of RMSD and RMSF during a natural physiological condition.
