Icaritin, an inhibitor of beta-site amyloid cleaving enzyme-1, inhibits secretion of amyloid precursor protein in APP-PS1-HEK293 cells by impeding the amyloidogenic pathway

Background Icaritin (ICT) is a prenylflavonoid derivative from Epimedium brevicornum Maxim. ICT has been shown to have neuroprotective effects. We investigate how ICT affects secretion of amyloid precursor protein (APP). Methods We exposed APP-PS1-HEK293 cells to ICT to investigate its effect on bet...

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Main Authors: Fei Feng, Yuanyuan Li, Nanqu Huang, Yong Luo
Format: Article
Language:English
Published: PeerJ Inc. 2019-12-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/8219.pdf
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spelling doaj-4261f434430b42f39ecc34ef91488ffb2020-11-25T01:45:14ZengPeerJ Inc.PeerJ2167-83592019-12-017e821910.7717/peerj.8219Icaritin, an inhibitor of beta-site amyloid cleaving enzyme-1, inhibits secretion of amyloid precursor protein in APP-PS1-HEK293 cells by impeding the amyloidogenic pathwayFei Feng0Yuanyuan Li1Nanqu Huang2Yong Luo3Department of Neurology, , , The First People’s Hospital of Zunyi and Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, ChinaNational Drug Clinical Trial Institution, The First People’s Hospital of Zunyi and Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, ChinaNational Drug Clinical Trial Institution, The First People’s Hospital of Zunyi and Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, ChinaDepartment of Neurology, , , The First People’s Hospital of Zunyi and Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, ChinaBackground Icaritin (ICT) is a prenylflavonoid derivative from Epimedium brevicornum Maxim. ICT has been shown to have neuroprotective effects. We investigate how ICT affects secretion of amyloid precursor protein (APP). Methods We exposed APP-PS1-HEK293 cells to ICT to investigate its effect on beta-site amyloid cleaving enzyme (BACE)1. Cell viability was evaluated by MTT and lactate dehydrogenase (LDH) assays. The half-maximal inhibitory concentration (IC50) of ICT for BACE1 was measured using fluorescence resonance energy transfer. Effects of ICT on the mRNA expression of APP were assessed by quantitative polymerase chain reaction, and protein expression was measured by western blotting and immunofluorescence. Results Icaritin inhibited BACE1 activity and IC50 was 5.70 ± 1.09 μM. Compared with the control group, at ICT concentrations of 5 μM and 10 μM, the viability increased and LDH leakage decreased in APP-PS1-293 cells. Also, mRNA expression of A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) increased, while that of BACE1 and presenilin-1 (PS1) decreased, upon ICT treatment. Western blotting and immunofluorescence confirmed that protein expression of ADAM10, BACE1 and PS1 showed the same trend. Expression of the APP fragments sAPPβ and C-terminal fragment β decreased, while that of sAPPα increased, upon ICT treatment. Expression of amyloid β peptides in APP-PS1-HEK293 cells was lower in ICT-treated groups compared with that in the control group. Conclusions Icaritin, as a BACE1 inhibitor, inhibits APP secretion in APP-PS1-HEK293 cells by impeding the amyloidogenic pathway.https://peerj.com/articles/8219.pdfAlzheimer’s diseaseIcaritinAmyloid-β peptideBeta-site amyloid cleaving enzyme 1Presenilin-1Amyloid precursor protein
collection DOAJ
language English
format Article
sources DOAJ
author Fei Feng
Yuanyuan Li
Nanqu Huang
Yong Luo
spellingShingle Fei Feng
Yuanyuan Li
Nanqu Huang
Yong Luo
Icaritin, an inhibitor of beta-site amyloid cleaving enzyme-1, inhibits secretion of amyloid precursor protein in APP-PS1-HEK293 cells by impeding the amyloidogenic pathway
PeerJ
Alzheimer’s disease
Icaritin
Amyloid-β peptide
Beta-site amyloid cleaving enzyme 1
Presenilin-1
Amyloid precursor protein
author_facet Fei Feng
Yuanyuan Li
Nanqu Huang
Yong Luo
author_sort Fei Feng
title Icaritin, an inhibitor of beta-site amyloid cleaving enzyme-1, inhibits secretion of amyloid precursor protein in APP-PS1-HEK293 cells by impeding the amyloidogenic pathway
title_short Icaritin, an inhibitor of beta-site amyloid cleaving enzyme-1, inhibits secretion of amyloid precursor protein in APP-PS1-HEK293 cells by impeding the amyloidogenic pathway
title_full Icaritin, an inhibitor of beta-site amyloid cleaving enzyme-1, inhibits secretion of amyloid precursor protein in APP-PS1-HEK293 cells by impeding the amyloidogenic pathway
title_fullStr Icaritin, an inhibitor of beta-site amyloid cleaving enzyme-1, inhibits secretion of amyloid precursor protein in APP-PS1-HEK293 cells by impeding the amyloidogenic pathway
title_full_unstemmed Icaritin, an inhibitor of beta-site amyloid cleaving enzyme-1, inhibits secretion of amyloid precursor protein in APP-PS1-HEK293 cells by impeding the amyloidogenic pathway
title_sort icaritin, an inhibitor of beta-site amyloid cleaving enzyme-1, inhibits secretion of amyloid precursor protein in app-ps1-hek293 cells by impeding the amyloidogenic pathway
publisher PeerJ Inc.
series PeerJ
issn 2167-8359
publishDate 2019-12-01
description Background Icaritin (ICT) is a prenylflavonoid derivative from Epimedium brevicornum Maxim. ICT has been shown to have neuroprotective effects. We investigate how ICT affects secretion of amyloid precursor protein (APP). Methods We exposed APP-PS1-HEK293 cells to ICT to investigate its effect on beta-site amyloid cleaving enzyme (BACE)1. Cell viability was evaluated by MTT and lactate dehydrogenase (LDH) assays. The half-maximal inhibitory concentration (IC50) of ICT for BACE1 was measured using fluorescence resonance energy transfer. Effects of ICT on the mRNA expression of APP were assessed by quantitative polymerase chain reaction, and protein expression was measured by western blotting and immunofluorescence. Results Icaritin inhibited BACE1 activity and IC50 was 5.70 ± 1.09 μM. Compared with the control group, at ICT concentrations of 5 μM and 10 μM, the viability increased and LDH leakage decreased in APP-PS1-293 cells. Also, mRNA expression of A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) increased, while that of BACE1 and presenilin-1 (PS1) decreased, upon ICT treatment. Western blotting and immunofluorescence confirmed that protein expression of ADAM10, BACE1 and PS1 showed the same trend. Expression of the APP fragments sAPPβ and C-terminal fragment β decreased, while that of sAPPα increased, upon ICT treatment. Expression of amyloid β peptides in APP-PS1-HEK293 cells was lower in ICT-treated groups compared with that in the control group. Conclusions Icaritin, as a BACE1 inhibitor, inhibits APP secretion in APP-PS1-HEK293 cells by impeding the amyloidogenic pathway.
topic Alzheimer’s disease
Icaritin
Amyloid-β peptide
Beta-site amyloid cleaving enzyme 1
Presenilin-1
Amyloid precursor protein
url https://peerj.com/articles/8219.pdf
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