Undescribed Meroterpenoids from Hypericum japonicum with Neuroprotective Effects on H_(2)O_(2) Insult SH-SY5Y Cells Targeting Keap1-Nrf2  

作　　者：Linzhen Hu Zhenzhen Wang Zhou Tong Ping Hu Luqi Kong Mengying Luo Xiao-Nian Li Yuexing Zhang Zhiyong Huang Yonghui zhang 

机构地区：[1]State Key Laboratory of Biocatalysis and Enzyme Engineering,National&Local Joint Engineering Research Centre of High-throughput Drug Screening Technology,Hubei Key Laboratory of Biotechnology of Traditional Chinese Medicine,School of Life Sciences,Hubei University,Wuhan,Hubei 430062,China [2]School of Pharmacy,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China [3]Kunming Institute of Botany,Chinese Academy of Sciences,Kunming,Yunnan 650204,China [4]College of Chemistry and Chemical Engineering,Hubei University,Wuhan,Hubei 430062,China [5]Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences.Tianjin 300308,China

出　　处：《Chinese Journal of Chemistry》2022年第11期1321-1330,共10页中国化学（英文版）

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).

摘　　要：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.

关 键 词：Hypericum japonicum Natural products TAUTOMERISM Neuroprotective activity Keap1-Nrf2-ARE pathway 

分 类 号：O62[理学—有机化学]