Inhibitory effect of piperlonguminine/ dihydropiperlonguminine on the production of amyloid beta and APP in SK-N-SH cells.
The study was undertaken to explore whether piperlonguminine/dihydropiperlonguminine could inhibit the production of amyloidbeta (Abeta) in human neuroblastoma cells (SK-N-SH) and to examine the underlying mechanism of this effect. Piperlonguminine/dihydropiperlonguminine components (1:0.8) were extracted from Futokadsura stem, and then used to treat SK-N-SH cells at three different concentrations: 3.13 microg/ml, 6.25 microg/ml and 12.50 microg/ml. Subsequently, the production of Abeta42 and Abeta40 were measured by Western blot analysis and enzyme linked immunosorbent assay (ELISA). On the other hand, the expressions of amyloid precursor protein (APP), Notch1 (Notch intracellular domain) and beta-site amyloid precursor protein cleavage enzyme (BACE-1) were also examined by Western blot assay. The activities of beta-secretase and gamma-secretase were detected at the same time. Furthermore, Abeta42 level was detected by immunocytochemistry staining. We demonstrated that the treatment of piperlonguminine/dihydropiperlonguminine could significantly decrease the levels of APP, Abeta42 and Abeta40 peptide in SK-N-SH cells, despite the fact that the activities of beta-secretase and gamma-secretase were not affected significantly. These data suggest that piperlonguminine/dihydropiperlonguminine components could significantly inhibit the level of APP, Abeta42 and Abeta40 peptide without affecting the activity of beta-secretase and gamma-secretase in SK-N-SH cells.
Qi
Hong-Shun
HS
Department of Cerebrovascular Disease, Qilu Hospital, Shandong University, Shandong, People's Republic of China.
Liu
Pei
P
Gao
Su-Qin
SQ
Diao
Zeng-Yan
ZY
Yang
Ling-Ling
LL
Xu
Jun
J
Qu
Xun
X
Han
En-Ji
EJ
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004148:Dioxolanes / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D051881:Receptor, Notch1 / Q000378:metabolism; D010881:Piperidones
D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016282:Aspartic Acid Endopeptidases; D004148:Dioxolanes; D004365:Drugs, Chinese Herbal; D051881:Receptor, Notch1; C497761:NOTCH1 protein, human; C509280:BACE1 protein, human; C498077:piperlongumine; D010881:Piperidones