Physalin B reduces Aβ secretion through down-regulation of BACE1 expression by activating FoxO1 and inhibiting STAT3 phosphorylation  

作　　者：ZHANG Wei BAI Shan-Shan ZHANG Qi SHI Ru-Ling WANG He-Cheng LIU You-Cai NI Tian-Jun WU Ying YAO Zhao-Yang SUN Yi WANG Ming-Yong 

机构地区：[1]School of Basic Medical Sciences,Xinxiang Medical University,Xinxiang 453003,China [2]Grade 2019,School of Basic Medical Sciences,Xinxiang Medical University,Xinxiang 453003,China [3]School of Public Health,Xinxiang Medical University,Xinxiang 453003,China [4]School of Life and Pharmaceutical Sciences,Dalian University of Technology,Panjin 124221,China [5]School of Basic Medical Sciences,Sanquan College of Xinxiang Medical University,Xinxiang 453003,China [6]School of Nursing Care,Xinxiang Medical University,Xinxiang 453003,China [7]Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China [8]School of Laboratory Medicine,Xinxiang Medical University,Xinxiang 453003,China [9]Xinxiang Key Laboratory of Immunoregulation and Molecular Diagnostics,Xinxiang 453003,China [10]Central Laboratory,the First Affiliated Hospital of Henan University of Science and Technology,Luoyang 471003,China

出　　处：《Chinese Journal of Natural Medicines》2021年第10期732-740,共9页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation(No.U1604108);Key Science and Technology Program of Henan Province(Nos.202102310020 and 182102311148);the Program for Innovative Research Team(in Science and Technology)in University of Henan Province(No.20IRTSTHN030);the Graduate Scientific Research Innovation Support Project of Xinxiang Medical University(No.YJSCX201866Y).

摘　　要：Physalin B(PB),one of the major active steroidal constituents of Solanaceae Physalis plants,has a wide variety of biological activities.We found that PB significantly down-regulatedβ-amyloid(Aβ)secretion in N2a/APPsw cells.However,the underlying mechanisms are not well understood.In the current study,we investigated the changes in key enzymes involved inβ-amyloid precursor protein(APP)metabolism and other APP metabolites by treating N2a/APPsw cells with PB at different concentrations.The results indicated that PB reduced Aβ secretion,which was caused by down-regulation of β-secretase(BACE1)expression,as indicated at both the protein and mRNA levels.Further research revealed that PB regulated BACE1 expression by inducing the activation of forkhead box O1(FoxO1)and inhibiting the phosphorylation of signal transducer and activator of transcription 3(STAT3).In addition,the effect of PB on BACE1 expression and Aβsecretion was reversed by treatment with FoxO1 siRNA and STAT3 antagonist S3I-201.In conclusion,these data demonstrated that PB can effectively down-regulate the expression of BACE1 to reduce Aβsecretion by activating the expression of FoxO1 and inhibiting the phosphorylation of STAT3.

关 键 词：Physalin B Β-AMYLOID BACE1 FOXO1 Alzheimer’s disease 

分 类 号：R965[医药卫生—药理学]